1 List of Abbreviations

ACEi	Angiotensin-converting enzyme inhibitor
ARB	Angiotensin receptor blocker
BB	Beta blocker
CCB	Calcium channel blocker
CDM	Common data model
dCCB	Dihydropyridine calcium channel blocker
HTN	Hypertension
LEGEND	Large-scale Evidence Generation and Evaluation across a Network of Databases
CDM	Common data model
MACE	Major adverse cardiovascular event
MDRR	Minimum detectable risk ratio
OHDSI	Observational Health Data Science and Informatics
OMOP	Observational Medical Outcomes Partnership
PS	Propensity score
RAS	Renin-angiotensin system
RCT	Randomized controlled trial
THZ	Thiazide or thiazide-like diuretics

2 Responsible Parties

2.1 Investigators

Investigator	Institution/Affiliation
Chungsoo Kim	Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA
Rohan Khera	Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA
George Hripcsak	Department of Biomedical Informatics, Columbia University, New York, NY, USA
Patrick B. Ryan	Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, USA
Harlan M. Krumholz	Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA
Marc A. Suchard	Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, USA
Yuan Lu*	Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA
* Principal Investigator

2.2 Disclosures

This study is undertaken within Observational Health Data Sciences and Informatics (OHDSI), an open collaboration. CK reported no disclosure. RK is a founder of Evidence2Health, and receives grant funding from the US National Institutes of Health. GH receives grant funding from the US National Institutes of Health and the US Food & Drug Administration and contracts from Johnson and Johnson. PBR reported being an employee and shareholder of Johnson and Johnson. HMK received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a co-founder of Refactor Health and HugoHealth, and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare & Medicaid Services and through Yale University from Johnson & Johnson. MAS receives grant funding from the US National Institutes of Health, the US Department of Veterans Affairs and the US Food & Drug Administration and contracts from Johnson and Johnson and IQVIA. YL received support from the Sentara Research Foundation, the National Heart, Lung, and Blood Institute (grant Nos. R01HL169954, R01HL169171) and the Patient-Centered Outcomes Research Institute (No. HM-2022C2-28354).

3 Abstract

Background and Significance: Hypertension is a major cause of morbidity and mortality globally and is associated with an elevated risk of cardiovascular events. Recommended antihypertensive agents can be applied to patients as a single agent (monotherapy) or in combination. In the case of combination, initial combination strategy can be considered, or stepped care strategy using a monotherapy followed by adding other agents use can be considered.

Many patients are unable to reach their target blood pressure with a monotherapy, therefore, they often use two or more medications in combination. Recent European hypertension guidelines recommend initial combination treatment for general patients with hypertension[1]; however, the US guidelines maintain a recommendation of stepped care for most patients with uncontrolled blood pressure[2]. Our team has already generated large-scale evidence comparing the effectiveness of each monotherapy[3] and initial combination therapy for hypertension[4]. Now, we will explore how the choice of step therapy medication affects patients’ cardiovascular and safety outcomes.

Study Aims: To determine real-world comparative effectiveness and safety of stepped care strategy of hypertension using health information encompassing millions of patients with hypertension, with a focus on individual at comorbidity risk and other key subgroups for treatment heterogeneity.

Study Description: We will conduct large-scale, systematic, observational studies to make pairwise comparisons of all stepped care regimens at the drug-, class- and population subgroup-level within our proposed Large-Scale Evidence Generations Across a Network of Database for Hypertension Stepped Care (LEGEND-HTNStepCare) initiative. LEGEND-HTNStepCare will leverage the Observational Health Data Sciences and Informatics (OHDSI) Community that provides access to a standing global network of administrative claims and electronic health record (EHR) data sources. LEGEND-HTNStepCare will study:

Population: Adult, hypertension patients who newly added a secondary antihypertensive agent for their uncontrolled blood pressure by monotherapy
Exposures: The exposure of interest is a combination of monotherapy with the following drug groups (except BB), followed by an addition of drugs from other groups. For example, patients with dCCB added after ACEI monotherapy.
- RAS agents:
  - ACEI: Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril
  - ARB: Azilsartan, Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan
- THZ: Chlorthalidone, Hydrochlorothiazide, Indapamide, Metolazone
- CCB:
  - dCCB: Amlodipine, Felodipine, Isradipine, Nicardipine, Nifedipine, Nisoldipine
  - ndCCB: Diltiazem, Verapamil
- BB (second-line only): Atenolol, Acebutolol, Betaxolol, Bisoprolol, Carvedilol, Labetalol, Metoprolol, Nadolol, Nebivolol, Penbutolol, Pindolol, Propranolol
Outcomes:
- Primary: 3- and 4-point major adverse cardiovascular events
- Secondary effectiveness: Acute myocardial infarction, hospitalization with heart failure, revascularization, stroke, sudden cardiac death
- Secondary safety: Abdominal pain, Abnormal weight gain, Abnormal weight loss, Acute pancreatitis, Acute renal failure, All-cause mortality, Angioedema, Anaphylactic reaction, Anemia, Anxiety, Bone fracture, Bradycardia, Cardiac arrhythmia, Chest pain or angina, Chronic kidney disease, Cough, Diarrhea, Dementia, Depression, Diarrhea, End stage renal disease, Fall, Gastrointestinal bleeding, Genitourinary infection, Gout, Headache, Hepatic failure, Hyperkalemia, Hypokalemia, Hyponatremia, Hypomagnesemia, Hypotension, Impotence, Joint pain, Malignant neoplasm, Measured renal dysfunction, Nausea, Neutropenia or agranulocytosis, Peripheral edema, Photosensitivity, Rash, Rhabdomyolysis, Syncope, Transient ischemic attack, Thrombocytopenia, Type 2 diabetes, Unstable angina, Vasculitis, Venous thromboembolism, Vertigo, Vomiting

For each data source and comparison, LEGEND-HTNStepCare will employ a state-of-the-art design:

Design: Observational: active-comparator, new-user cohort study

Our systematic framework will address residual confounding, publication bias and \(p\)-hacking using data-driven, large-scale propensity adjustment for measured confounding, a large set of negative control outcome experiments to address unmeasured and systematic bias, prespecification and full disclosure of hypotheses tested and their results. These approaches capitalize on mature OHDSI open source resources and a large body of clinical and quantitative research that the LEGEND-HTNStepCare investigators originated and continue to drive. Finally, LEGEND-HTNStepCare is dedicated to open science and transparency and will publicly share all our analytic code from reproducible cohort definitions through turn-key software, enabling other research groups to leverage our methods, data, and results in order to verify and extend our findings.

4 Amendments and Updates

Number	Date	Section of study protocol	Amendment or update	Reason
1	14-Apr-2024	All	Update	Initial draft
2	15-Feb-2025	All	Update	Protocol refinement

5 Milestones

Milestone	Planned / actual date
Protocol online release	31-Mar-2025 /
Protocol registration
Collecting data partners
Start of analysis
End of analysis
Results presentation

6 Rationale and Background

Over 100 million US adults have hypertension, a leading cause of mortality and morbidity, and 70% of them cannot achieve adequate blood pressure control with monotherapy alone[5]. Although recent clinical practice guidelines suggest initiating therapy with two drugs[1,2,6], more than 50% of people currently treated for hypertension start with a single medication [7,8]. For these patients, clinical guidelines propose adding a second antihypertensive drug for treatment escalation[2,7–9]. However, the guidelines provide little guidance on which specific agents to add for which patients. There are no large randomized controlled trials (RCT) to guide recommendations about the choice of the second drug[[2];]. RCTs comparing antihypertensive drugs are not only expensive and time-consuming, but also cannot possibly test all the relevant drug combinations recommended by the guidelines. Given the abundance of potential strategies, there is a critical need to generate real-world evidence to guide the choice of comparators in future RCTs and to support guideline recommendations. Advances in observational research design using real-world data provides an opportunity to produce high-quality evidence through strategies that support causal inference, enhance generalizability, and minimize bias. While this evidence will not supersede RCT evidence, it can identify promising directions for trials and provide Level of Evidence B for guideline recommendations[10]. Such research can be purposeful, pre-specified, and have strategies to prevent publication bias, p-hacking, and findings due to chance. In our prior work, we have successfully demonstrated how these methods can be applied to evaluate the effectiveness and safety of first-line antihypertensive monotherapies[3,11–14]. This will be the first study that applies these massive real-world datasets and reproducible methods to comprehensively evaluate the effectiveness and safety of the second antihypertensive agents added to monotherapy as a hypertension stepped care.

7 Study Objectives

The overall objective in this protocol is to determine the comparative effectiveness and safety of the stepped care strategy in real-world settings. The central hypothesis is that there is heterogeneity in the effectiveness and safety of the secondary antihypertensive agent, and the optimal choice depends on patient characteristics and the initial therapy. Our long-term goal is to produce real-world evidence to inform decisions about RCTs for hypertension treatment escalation and to provide the highest quality non-randomized evidence to support guideline recommendations. The approach is distinctive because of the breadth and depth of data, and the use of state-of-the-art observational research methods to produce high-quality evidence. Our preliminary data demonstrate a large variation in prescription patterns of the second agents added to monotherapy[8], providing ample opportunity to leverage practice variation to test our hypothesis. The following three specific aims are proposed:

To determine the comparative effectiveness of the stepped-care strategy on major cardiovascular outcomes (e.g., myocardial infarction, stroke, heart failure).
To determine the comparative risk of the second antihypertensive agents on potential drug-related adverse events (e.g., acute renal failure, angioedema, gastrointestinal bleeding, hyperkalemia).
To assess heterogeneity in effectiveness and safety of the stepped care strategy among key patient subgroups defined by age, sex, race, ethnicity, and comorbidity.

8 Research Methods

LEGEND-HTNStepCare will execute three systematic, large-scale observational studies of second line antihypertensive agents to estimate the relative risks of cardiovascular effectiveness and safety outcomes.

The Class-vs-Class Study will provide all pairwise comparisons between the stepped care combination with antihypertensive agent classes to evaluate their comparative effects on cardiovascular risk (Objective 1) and patient-centered safety outcomes (Objective 2);
The Drug-vs-Drug Study will furnish head-to-head pairwise comparisons between individual agents within and across class in stepped care combination (both Objectives 1 and 2); and
The Heterogeneity Study will refine these comparisons for hypertension patients for important subgroups (Objective 3).

In contrast to a single comparison approach, LEGEND-HTNStepCare will provide a comprehensive view of the findings and their consistency across populations, drugs, and outcomes. We will model each study on our successful collaborative research evaluating the comparative effectiveness of antihypertensives monotherapy previously published in The Lancet [3].

Table 8.1 list the major classes of antihypertensive agents and those ingredients lisenced in the U.S. within each class.

For each comparison, we are interested in the relative risk of each of the cardiovascular and safety outcomes described in Section 8.5.

Table 8.1: Antihypertensive drug classes and individual agents within each class
ACEI	ARB	dCCB	ndCCB	Thiazide	BB
benazepril	azilsartan	amlodipine	diltiazem	chlorthalidone	acebutolol
captopril	candesartan	felodipine	verapamil	hydrochlorothiazide	atenolol
enalapril	eprosartan	isradipine		indapamide	betaxolol
fosinopril	irbesartan	nicardipine		metolazone	bisoprolol
lisinopril	losartan	nifedipine			carvedilol
moexipril	olmesartan	nisoldipine			labetalol
perindopril	telmisartan				metoprolol
quinapril	valsartan				nebivolol
ramipril					nadolol
trandolapril					penbutolol
					pindolol
					propranolol

8.1 Study Design

For each study, we will employ an active comparator, new-user cohort design[15]. New-user cohort design is advocated as the primary design to be considered for comparative effectiveness and drug safety. By identifying patients who start a new treatment course and using therapy initiation as the start of follow-up, the new-user design models a randomized controlled trial (RCT) where treatment commences at the index study visit. Exploiting such an index date allows a clear separation of baseline patient characteristics that occur prior to index date and are usable as covariates in the analysis without concern of inadvertently introducing mediator variables that arise between exposure and outcome. Excluding prevalent users as those without a sufficient washout period prior to first exposure occurrence further reduces bias due to balancing mediators on the causal pathway, time-varying hazards, and depletion of susceptibles. Our systematic framework across studies further will address residual confounding, publication bias, and p-hacking using data-driven, large-scale propensity adjustment for measured confounding, a large set of negative control outcome experiments to address unmeasured and systematic bias, and full disclosure of hypotheses tested. Figure 8.1 below illustrates our design for all studies that the following sections describe in more detail.

Figure 8.1: Schematic of LEGEND-HtnStepCare new-user cohort design for the Class-vs-Class, Drug-vs-Drug and Heterogeneity studies.

8.2 Data Sources

We will execute LEGEND-HTNStepCare as a series of OHDSI network studies. All data partners within OHDSI are encouraged to participate voluntarily and can do so conveniently, because of the community’s shared Observational Medical Outcome Partnership (OMOP) common data model (CDM) and OHDSI tool-stack [16]. Many OHDSI community data partners have already committed to participate and we will recruit further data partners through OHDSI’s standard recruitment process, which includes protocol publication on OHDSI’s GitHub, an announcement in OHDSI’s research forum, presentation at the weekly OHDSI all-hands-on meeting and direct requests to data holders.

In Table 8.2, we report a brief description of already committed databases and their size of the population it represents and its patient capture process and start date. While the earliest patient capture begins in 2000 (VA), the vast majority come from the 2010s to today, providing a decade of HTN treatment coverage. The US population include those publicly insured, enriched for older individuals (VA) and racially diverse (VA, Sentara). The US data sources may capture the same patients across multiple sources. Different views of the same patients are an advantage in capturing the diversity of real-world health events that patients experience. All data sources will receive institutional review board approval or exemption for their participation before executing LEGEND-HTNStepCare.

Table 8.2: Committed LEGEND-HtnStepCare data sources and the populations they cover.
Data source	Population	Patients	History	Data capture process and short description
Electronic health records (EHRs)
Yale New Haven Health System (YNHHS)	Academic medical center patients	2M	2013 –	General practice, specialists and inpatient hospital services from the YNHHS in Connecticut.
Sentara Healthcare (Sentara)	Patients in a non-profit integrated healthacare system, all ages, racially diverse	7.8M	2010 –	The largest integrated health system in Northern Virginia with 12 hostpials and 556 outpatient sites. Sentara Healthcare serves the Hampton Roads region of Virginia, an area with 1.7 million residents, of which 31% are African American and 8% are Hispanic.
Department of Veterans Affairs (VA)	Veterans, older, racially diverse	12M	2000 –	National VA health care system, the largest integrated provider of medical services in the US, provided at 170 VA medical centers and 1,063 outpatient sites.
Columbia University Irving Medical Center (CUIMC)	Academic medical center patients, racially diverse	6M	1989 –	General practice, specialists and inpatient hospital services from the New York-Presbyterian hospital and affiliated academic physician practices in New York.
Optum Electronic Health Records (PanTher)	US general Population, all ages	93M	2006 –	Clinical information, prescriptions, lab results, vital signs, body measurements, diagnoses and procedures derived from clinical notes using natural language processing.

8.3 Study Population

We will include all subjects in a data source who meet inclusion criteria for the stepped care exposure cohorts. Broadly, these cohorts will consist of hypertension patients with any of ACEis, ARBs, THZs, and CCBs previous as a first line hypertension treatment. We describe specific definitions of exposure cohorts for each study in the following sections.

8.4 Exposure Comparators

8.4.1 Class-vs-Class Study comparisons

The Class-vs-Class Study will construct twenty-three exposure cohorts for secondary use of any drug ingredient within the major classes in Table 8.1. Cohort entry (index date) for each patient is their first observed exposure to any drug ingredient for secondary added drug classes (different to primary class). Consistent with an idealized target trial for hypertension therapy and cardiovascular risk, inclusion criteria for patients based on the index date will include:

Hypertension diagnosis but no secondary HTN diagnosis before the index date;
At least 1 year of observation time before the index date (to improve new-user sensitivity);
At least one prescription of first antihypertensive agents before 30 days earlier than the index date;
No single use of antihypertensives at the index date;
No prior drug exposure to a comparator antihypertensive agent; and
No other antihypertensive agents (other diuretics: loop diuretics/K+ sparing diuretics/aldosterone antagonists; direct renin inhibitor; alpha-1 blocker; central alpha-2 agonist and other centrally acting drugs; direct vasodilators).

We will construct and compare separately cohorts patients either with

At least 1 months use of first-line antihypertensive agents use before the index date.

In this case, a month of first-line antihypertensive agents is consistent with 2017 AHA/ACC guidelines. We will use cohort diagnostics, such as achieving covariate balance and clinical empirical equipoise between exposure cohorts (Section 9) and stakeholder input to guide the possible need to exclude other prior diagnoses, such as heart failure.

Of note, the inclusion criteria do not directly incorporate quantitative measures of blood pressure control, such as elevated blood pressure; such laboratory values are irregularly captured in even EHR data sources. The ACC/AHA guidelines advise escalating to add a second agent when average BP is more than 20/10 mmHg above their BP target. We will conduct sensitivity analyses involving available BP measurements to demonstrate their balance between exposure cohorts (described later in Section 9). In the unlikely event that balance is not met, we will consider an inclusion criterion of BP >130/80 (or 140/90) mmHg within 6 months before the index.

For each data source, we will then execute all 42 pairwise class comparisons for which the data source yields \(\ge\) 1,000 patients in each arm. Appendix A. 1. reports the complete OHDSI ATLAS cohort description for new-users of thiazide or thiazide-like diuretics with the first line ACEI. This description lists complete specification of cohort entry events, additional inclusion criteria, cohort exit events, and all associate standard OMOP CDM concept code sets used in the definition. ATLAS automatically translates these definitions into network-deployable SQL source code. Significantly fewer numbers of patients strongly suggest data source-specific differences in prescribing practices that may introduce residual bias and sufficient sample sizes are required to construct effective propensity score models.

8.4.2 Drug-vs-Drug Study comparisons

The Drug-vs-Drug Study will construct 1,070 exposure cohorts for new-users of each drug ingredient in Table 8.1. We will apply the same cohort definition, inclusion criteria and patient count minimum as described in Section 8.4.1.

Theoretically, \(\binom{1070}{2}\) = 571,915 comparisons are possible. However, we want to take into account the fact that Class-vs-Class comparisons will be performed and clinical situation when stepped care is performed. Therefore, we will focus primary clinical interpretation and scientific publishing to the 3,400 comparisons where the first-line drug is the same and the second line drug is a different ingredient within the same class, e.g, First amlodipine adding acebutolol vs. First amlodipine adding atenolol.

Appendix A.5 reports the complete OHDSI ATLAS cohort description for new-users of acebutolol added to amlodipine monotherapy. Again, we programmatically construct all new-user drug-level cohort and automatically translate into SQL.

8.4.3 Heterogeneity Study comparisons

The Heterogeneity Study will further stratify all class- and drug-level exposure cohorts in Section 8.4.1 and 8.4.2 by clinically important patient characteristics that modify cardiovascular risk of relative treatment heterogeneity to provide patient-focused treatment recommendations. These factors will include:

Age (18 - 44 / 45 - 64 / \(\ge\) 65 at the index date)
Sex (women / men)
Race (White / African American or black / Hispanic)

Appendix A. 3 presents complete OHDSI ATLAS specifications for these subgroups.

8.4.4 Validation

We will validate exposure cohorts and aggregate drug utilization using comprehensive cohort characterization tools against data sources. Chief among these tools stands OHDSI’s CohortDiagnostics package (https://github.com/OHDSI/CohortDiagnostics). For any cohort and data source mapped to OMOP CDM, this package systematically generates incidence new-user rates (stratified by age, gender, and calendar year), cohort characteristics (all comorbidities, drug use, procedures, health utilization) and the actual codes found in the data triggering the various rules in the cohort definitions. This can allow researchers and stakeholders to understand the heterogeneity of source coding for exposures and health outcomes as well as the impact of various inclusion criteria on overall cohort counts (details described in Section 9).

8.5 Outcomes

We originally identified outcomes for LEGEND-HTNStepCare from clinical trial endpoints from clinical guidelines and systematic reviews. We augmented these with adverse events from US structured product labels of hypertension drugs. For each outcome, we developed an operational phenotype definition to determine if observational data could in fact support evaluation of the outcome. We used the same approach to design, implement, and evaluate all phenotypes. Specifically, clinical guidelines and systematic review of clinical trial of hypertension treatments informed our clinical definition of cardiovascular outcomes. We developed all exposure cohorts according to the definition itself through ATLAS. We did not perform source record verification or other validation methods.

Across all data sources and pairwise exposure cohorts, we will assess relative risks of 32 cardiovascular and patient-centered outcomes (Table 8.3). Primary outcomes of interest are:

3-point major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, and sudden cardiac death, and
4-point MACE that additionally includes heart failure hospitalization.

Secondary outcomes include:

individual MACE components,

In data sources with laboratory measurements, secondary outcomes further include:

Blood pressure control

We will also study secondary antihypertensive agent adverse events and safety concerns highlighted in the 2017 ACC/AHA guidelines and from RCTs, including SPRINT trial. We will employ the same level of systematic rigor in studying outcomes regardless of their primary or secondary label. A majority of outcome definitions have been previously implemented and validated in our own work, based heavily on prior development by others (see prior development in Table 8.3).

To assess across-source consistency and general clinical validity, we will characterize outcome incidence, stratified by age, sex and index year for each data source.

We will employ the same level of systematic rigor in studying outcomes regardless of their primary or secondary label.

A majority of outcome definitions have been previously implemented and validated in our own work [17–22] based heavily on prior development by others (see references in Table 8.3 [18,19,21–24,24–26,26,27,27–29,29,30,30,31,31,32,32,33,33,34,34–84,84–172,173 ]). To assess across-source consistency and general clinical validity, we will characterize outcome incidence, stratified by age, sex and index year for each data source.

Table 8.3: LEGEND-HtnSteppedCare study outcomes
Phenotype	Brief logical description	Prior development
Cardiovascular outcomes
3-point MACE	Condition record of acute myocardial infarction, hemorrhagic or ischemic stroke or sudden cardiac death during an inpatient or ER visit	[23–35]
4-point MACE	3-Point MACE \(+\) inpatient or ER visit (hospitalization) with heart failure condition record	[19,23–41]
Abdominal pain	Abdominal pain condition record of any type; successive records with > 90 day gap are considered independent episodes	[42–44]
Abnormal weight gain	Abnormal weight gain record of any type; successive records with > 90 day gap are considered independent episodes; note, weight measurements not used	[45]
Abnormal weight loss	Abnormal weight loss record of any type; successive records with > 90 day gap are considered independent episodes; note, weight measurements not used	[46]
Acute myocardial infarction	Condition record of acute myocardial infarction during an inpatient or ER vist	[23–28]
Acute pancreatitis	Condition record of acute pancreatitis during an inpatient or ER visit	[47–50]
Acute renal failure	Condition record of acute renal failure during an inpatient or ER visit	[21,51–58]
All-cause mortality	Death record of any type	[26,59,60]
Anaphylactoid reaction	Anaphylactoid reaction condition record during an inpatient or ER visit; successive records with >7 day gap are considered independent episodes	[61,62]
Patient-centered safety outcomes
Anemia	The first condition record of anemia	[63–65]
Angioedema	Angioedema condition record during an inpatient or ER visit; successive records with >7 day gap are considered independent episodes	[66,67]
Anxiety	The first condition record of anxiety, which is followed by another anxiety condition record or a drug used to treat anxiety	[68–71]
Bone fracture	Bone fracture condition record of any type; successive records with > 90 day gap are considered independent episodes
Bradycardia	The first condition record of bradycardia, which is followed by another bradycardia condition record	[72,73]
Cardiac arrhythmia	The first condition record of cardiac arrhythmia, which is followed by another cardiac arrhythmia condition record, at least two drug records for a drug used to treat arrhythmias, or a procedure to treat arrhythmias	[35,74–77]
Chest pain	The first condition record of chest pain or angina	[78]
Chronic kidney disease	The first condition record of chronic kidney disease, which is followed by either another chronic kidney disease condition record or a dialysis procedure or observation	[53,79–86]
Cough	Cough condition record of any type; successive records with > 90 day gap are considered independent episodes	[87,88]
Decreased libido	The first condition record of decreased libido	[89]
Dementia	The first condition record of dementia	[90–96]
Depression	The first condition record of depression, which is followed by another depression condition record, at least two drugs used to treat depression without another indication, or two psychotherapy procedures	[69,70,96–100]
Diarrhea	Diarrhea condition record of any type; successive records with > 30 day gap are considered independent episodes	[101–103]
End stage renal disease	End stage renal disease (ESRD) is defined by at least one diagnosis in any setting, followed by at least one additional diagnosis or a dialysis-related procedure within 90 days	[50,84,104]
Fall	Fall condition record of any type; successive records with >180 day gap are considered independent episodes	[105–107]
Gastrointestinal bleeding	Gastrointestinal hemorrhage condition record during an inpatient or ER visit; successive records with > 30 day gap are considered independent episodes	[108–114]
Genitourinary infection	Condition record of any type of genital or urinary tract infection during an outpatient or ER vists	[115]
Gout	The first condition record of gout	[116–119]
Headache	Headache condition record of any type; successive records with > 30 day gap are considered independent episodes	[120,121]
Hemorrhagic stroke	Intracranial, cerebral or subarachnoid hemorrhage condition record during an inpatient or ER visit; successive records with > 180 day gap are considered independent episodes	[29–33]
Hepatic failure	The first condition record of hepatic failure, necrosis, or coma	[122–129]
Hospitalization with heart failure	Inpatient or ER visit with heart failure condition record	[19,36–41]
Hyperkalemia	Condition record for hyperkalemia or potassium measurements > 5.6 mmol/L; successive records with >90 day gap are considered independent episodes	[130–132]
Hypoglycemia	Hypoglycemia condition record of any type; successive records with > 90 day gap are considered independent episodes	[133]
Hypokalemia	Hypokalemia condition record of any type; successive records with > 90 day gap are considered independent episodes	[134]
Hypomagnesemia	Hypomagnesemia condition record of any type; successive records with > 90 day gap are considered independent episodes	[135,136]
Hyponatremia	Hyponatremia condition record of any type; successive records with > 90 day gap are considered independent episodes	[137,138]
Hypotension	Hypotension condition record of any type; successive records with > 90 day gap are considered independent episodes	[139]
Impotence	The first condition record of impotence	[140–143]
Ischemic stroke	Ischemic stroke condition record during an inpatient or ER visit; successive records with > 180 day gap are considered independent episodes	[24,26,27,29,34]
Joint pain	Joint pain condition record of any type; successive records with > 90 days gap are considered independent episodes
Lower extremity amputation	Procedure record of below knee lower extremity amputation during inpatient or outpatient visit	[19,22]
Malignant neoplasm	First occurrence of malignant neoplasm, followed by at least one additional diagnosis of the same type (melanoma, bladder, brain, breast, colon and rectum, kidney, leukemia, liver, lung, lymphoma, multiple myeloma, ovary, pancreas, prostate, thyroid, uterus, myelodysplastic syndrome)	[144–156]
Measured renal dysfunction	First creatinine measurement with value > 3 mg/dL	[58]
Nausea	Nausea condition record of any type; successive records with > 30 day gap are considered independent episodes	[108,157,158]
Neutropenia or agranulocytosis	The first condition record of neutropenia or agranulocytosis	[159,160]
Peripheral edema	Edema condition record of any type; successive records with > 180 day gap are considered independent episodes
Photosensitivity	Condition record of drug-induced photosensitivity during any type of visit
Rash	Rash condition record of any type; successive records with >90 day gap are considered independent episodes	[66]
Revascularization	Procedure record of percutaneous coronary intervention or coronary artery bypass grafting during an inpatient or ER visit	[18]
Rhabdomyolysis	Rhabdomyolysis condition record or muscle disorder condition record with creatine measurement 5*ULN during an inpatient or ER visit; successive records with >90 day gap are considered independent episodes	[161,162]
Stroke	Condition record of hemorrhagic or ischemic stroke during an inpatient or ER visit	[29–34]
Sudden cardiac death	Condition record of sudden cardiac death during an inpatient or ER visit	[26,35]
Syncope	Syncope condition record of any type; successive records with > 180 day gap are considered independent episodes	[139]
Thrombocytopenia	The first condition record of thrombocytopenia	[163–165]
Transient ischemic attack	Transient ischemic attack condition record during an inpatient or ER visit; successive records with > 30 day gap are considered independent episodes	[29,34]
Type 2 diabetes mellitus	The first condition record of Type 2 Diabetes Mellitus, which is followed by another Type 2 Diabetes Mellitus condition record, at least 2 drugs used to treat Type 2 diabetes, or at least 2 HbA1c measurements with value >6.5%	[96,166–168]
Venous thromboembolism	Venous thromboembolism condition record of any type; successive records with > 180 day gap are considered independent episodes	[169–172]
Vertigo	The first condition record of vertigo	[173]
Vomiting	Vomiting condition record of any type; successive records with > 30 day gap are considered independent episodes	[108,157,158]

8.6 Analysis

8.6.1 Contemporary utilization of drug classes and individual agents

For all cohorts in the three studies, we will describe overall utilization as well as temporal trends in the use of each drug class and agents within the class. Further, we will evaluate these trends in patient groups by age (18-44 / 45-64 / \(\ge\) 65 years), sex, race and geographic regions. These data will provide insight into the current patterns of use ad possible disparities. These data are critical to guide the real-world application of treatment decision pathways for the treatment of HTN patients.

Specifically, we will calculate and validate aggregate drug utilization using the OHDSI’s CohortDiagnostics package against data sources. The CohortDiganostics package works in two steps: 1) Generate the utilization results and diagnostics against a data source and 2) Explore the generated utilization and diagnostics in a user-friendly graphical interface R-Shiny app. Through the interface, one can explore patient profiles of a random sample of subjects in a cohort. These diagnostics provide a consistent methodology to evaluate cohort definition and phenotype algorithms across a variety of observational databases. This will enable researchers and stakeholders to become informed on the appropriateness of including specific data sources within analyses, exposing potential risks related to heterogeneity and variability in patient care delivery that, when not addressed in the design, could result in errors such as high correlated covariates in propensity score matching of a target and a comparator cohort. Thus, the added value of this approach is two-fold in terms of exposing data quality for a study question and ensuring face validity checks are performed on proposed covariates to be used for balancing propensity scores.

8.6.2 Relative risk of cardiovascular and patient-centered outcomes

We will execute a systematic process to estimate the relative risk of cardiovascular and patient-centered outcomes between new-users of second-line HTN agents. The process will adjust for measured confounding, control from further residual (unmeasured) bias and accommodate important design choices to best emulate the nearly impossible to execute, idealized RCT that our stakeholders envision across data source populations, comparators, outcomes, and subgroups.

To adjust for potential measured confounding and improve the balance between cohorts, we will build large-scale propensity score (PS) models for each pairwise comparison and data source using a consistent data-driven process through regularized regression. This process engineers a large set of predefined baseline patient characteristics, including age, gender, race, index month/year and other demographics and prior conditions, drug exposures, procedures, laboratory measurements and health service utilization behaviors, to provide the most accurate prediction of treatment and balance patient cohorts across many characteristics. Construction of condition, drug, procedures and observations include occurrences within 365, 180, and 30 days prior to index date and are aggregated at several SNOMED (condition) and ingredient/ATC class (drug) levels. Other demographic measures include comorbidity risk scores (Charlson, DCSI, CHADS2, CHAD2VASc). From prior work, feature counts have ranged in the 1,000s-10,000s, and these large-scale PS models have outperformed hdPS in simulation and real-world examples.

We will:

Exclude patients who have experienced the outcome prior to their index date,
Stratify and variable-ratio match patients by PS, and
Use Cox proportional hazards models

to estimate hazard ratios (HRs) between alternative target and comparator treatments for the risk of each outcome in each data source. In addition, we will perform a sensitivity analysis that does not exclude individuals who previously experienced a blood pressure control outcome before the index date. The regression will condition on the PS strata/matching-unit with treatment allocation as the sole explanatory variable and censor patients at the end of their time-at-risk (TAR) or data source observation period. We will prefer stratification over matching if both sufficiently balance patients (see Section 9), as the former optimizes patient inclusions and thus generalizability.

We will execute each comparison using three different TAR definitions, reflecting different and important causal contrasts:

Intent-to-treat (TAR: index + 1 → end of observation) captures both direct treatment effects and (long-term) behavioral/treatment changes that initial assignment triggers [174];
On-treatment-1 (TAR: index + 1 → treatment discontinuation) is more patient-centered [175] and captures direct treatment effect while allowing for escalation with additional antihypertensive agents; and
On-treatment-2 (TAR: index + 1 → discontinuation or escalation with other antihypertensive agents) carries the least possible confounding with other concurrent antihypertensive agents.

Our “on-treatment” is often called “per-protocol”. Systematically executing with multiple causal contrasts enables us to identify potential biases that missing prescription data, treatment escalation and behavioral changes introduce, while preserving the ease of intent-to-treat interpretation and power if the data demonstrate them as unbiased. Appendix A.3 reports the modified cohort exit rule for the on-treatment-2 TAR.

We will aggregate HR estimates across non-overlapping data sources to produce meta-analytic estimates using a random-effects meta-analysis. The classic meta-analysis assumes that per-data source likelihoods are approximately normally distributed. This assumption fails when outcomes are rare as we expect for some safety events. Here, our recent research shows that as the number of data sources increases, the non-normality effect increases to where coverage of 95% confidence intervals (CIs) can be as low as 5%. To counter this, we will also apply a Bayesian meta-analysis model that neither assumes normality nor requires patient-level data sharing by building on composite likelihood methods and enables us to introduce appropriate overlap weights between data sources.

Residual study bias from unmeasured and systematic sources often remains in observational studies even after controlling for measured confounding through PS-adjustment. For each comparison-outcome effect, we will conduct negative control (falsification) outcome experiments, where the null hypothesis of no effect is believed to be true, using approximately 100 controls. We identified these controls through a data-rich algorithm that identifies prevalent OMOP condition concept occurrences that lack evidence of association with exposures in published literature, drug-product labeling and spontaneous reports, and were then adjudicated by clinical review. We previously validated 60 of the controls in LEGEND-HTN. Appendix C lists these negative controls and their OMOP condition concept IDs. Using the empirical null distributions from these experiments, we will calibrate each study effect HR estimate, its 95% CI and the p-value to reject the null hypothesis of no differential effect. We will declare an HR as significantly different from no effect when its calibrated p < 0.05 without correcting for multiple testing. Finally, blinded to all trial results, study investigators will evaluate study diagnostics for all comparisons to assess if they were likely to yield unbiased estimates (Section 9).

8.6.3 Sensitivity analyses and missingness

Because of the potential confounding effect of blood pressure at baseline between treatment choice and outcomes and to better understand the impact of limited blood pressure level measurements on effectiveness and safety estimation that arises in some EHR data, we will perform pre-specified sensitivity analyses for all studies within data sources that contain reliable blood pressure measurements. Within a study, for each exposure pair, we will first rebuild PS models where we additionally include baseline blood pressure as patient characteristics, stratify or matching patients under the new PS models that directly adjust for potential confounding by blood pressure and then estimate effectiveness and safety HRs.

A limitation of the Cox model is that no doubly robust procedure is believed to exist for estimating HRs, due to their non-collapsibility. Doubly robust procedures combine baseline patient characteristic-adjusted outcome and PS models to control for confounding and, in theory, remain unbiased when either (but not necessarily both) model is correctly specified. Doubly robust procedures do exist for hazard differences, and we will validate the appropriateness of our univariable Cox modelling by comparing estimate differences under an additive hazards model with and without doubly robust-adjustment. In practice, however, neither the outcome nor PS model is correctly specified, leading to systematic error in the observational setting.

Missing data of potential concern are patient demographics (gender, age, race) for our inclusion criteria. We will include only individuals whose baseline eligibility can be characterized that will most notably influence race subgroup assessments in the Heterogeneity Study. No further missing data can arise in our large-scale PS models because all features, with the exception of demographics, simply indicate the presence or absence of health records in a given time-period. Finally, we limit the impact of missing data, such as prescription information, relating to exposure time-at-risk by entertaining multiple definitions [176]. In all reports, we will clearly tabulate numbers of missing observations and patient attrition.

9 Sample Size and Study Power

Within each data source, we will execute all comparisons with \(\ge\) 1,000 eligible patients per arm. Blinded to effect estimates, investigators and stakeholders will evaluate extensive study diagnostics for each comparison to assess reliability and generalizability, and only report risk estimates that pass [177,178]. These diagnostics will include

Minimum detectable risk ratio (MDRR) as a typical proxy for power,
Preference score distributions to evaluate empirical equipoise [179] and population generalizability,
Extensive patient characteristics to evaluate cohort balance before and after PS-adjustment,
Negative control calibration plots to assess residual bias, and
Kaplan-Meier plots to examine hazard ratio proportionality assumptions.

We will define cohorts to stand in empirical equipoise if the majority of patients carry preference scores between 0.3 and 0.7 and to achieve balance if all after-adjustment characteristics return absolute standardized mean differences \(<\) 0.1 [180].

10 Strengths and Limitations

10.1 Strengths

The strengths of the LegendHtnStepCare study stem from the research question, the methodologies employed, and our commitment to open science: * This study is poised to be the first to systematically address the critical clinical question: What are the relative benefits and risks of adding a second antihypertensive drug to monotherapy in patients with hypertension? * We are employing massive, diverse real-world datasets and cutting-edge observational research methods to provide comprehensive estimates of effectiveness and safety for second antihypertensive drugs added to monotherapy. These tools have previously evaluated antihypertensive monotherapies, but have not been used to assess the addition of a second drug when monotherapy is insufficient for managing hypertension. * Unlike typical observational research, this study will minimize residual bias by employing reproducible methods to mitigate observed confounding. We will enhance transparency by reporting diagnostics such as empirical equipoise and covariate balance, and by using a large set of control outcomes to detect and correct for any remaining systematic errors. This approach marks a significant advancement in observational research. * We will assess antihypertensive medications at both class and individual drug levels, evaluating effectiveness and safety across patient subgroups defined by demographic and clinical characteristics. This comprehensive approach has not been adequately explored in previous studies. * Our commitment to Open Science includes making all study artifacts—such as the study protocol, analytical code, and full results—publicly available. We will also provide real-time access to these materials for external analysis and interpretation, a practice that goes beyond the transparency typically seen in past studies.

10.2 Limitations

Some additional aspects merit consideration: * Residual Confounding: Despite our sophisticated analytic approach and diagnostics, residual confounding remains a possibility. We anticipate that ongoing and future randomized controlled trials (RCTs) will shed further light on this issue. We will use two distinct methods to triangulate residual confounding: large-scale propensity score (PS) adjustment and the use of numerous negative controls. Our PS adjustment incorporates tens of thousands of baseline covariates for matching and stratification. * Medication Adherence: Merely having a prescription does not guarantee medication consumption. We will conduct sensitivity analyses using pharmacy refill data to infer adherence, and perform on-treatment analysis to adjust for potential discrepancies in adherence across different drug classes. * Dose Variability: We will conduct sensitivity analyses among patients maintaining consistent dosing throughout the on-treatment period to account for differences in dosing and potency. * Medication Indication: Some patients, like those with congestive heart failure, might be prescribed antihypertensive medications for reasons other than lowering blood pressure. We will exclude such patients from the study cohort during sensitivity analyses. * Informative Censoring: There is a risk that censoring at the end of the on-treatment periods could be informative. We will utilize extensive negative controls to detect and adjust for any potential bias introduced by this censoring. * Overlap of Patients Across Databases: While our study is designed to minimize patient overlap across databases by adhering to federated analytic principles, we acknowledge that some overlap may occur. We will ensure that patient experiences are reported distinctly for each database.

11 Protection of Human Subjects

LEGEND-HTNStepCare does not involve human subject research. The project does, however, use human data collected during routine healthcare provision. Most often the data are de-identified within data source. All data partners executing the LEGEND-HtnStepCare studies within their data sources will have received institutional review board (IRB) approval or waiver for participation in accordance to their institutional governance prior to execution (see Table 11.1). LEGEND-HTNStepCare executes across a federated and distributed data network, where analysis code is sent to participating data partners and only aggregate summary statistics are returned, with no sharing of patient-level data between organizations.

Table 11.1: IRB approval or waiver statement from partners.
Data source	Statement
Yale New Haven Health System (YNHHS)	Use of the YNHHS EHR data source was approved by the Yale University Institutional Review Board as an OHDSI network study (IRB#2000026013).
Sentara Healthcare System (Sentara)	Use of the Sentara EHR data source was approved by the Senatara Health Institutional Review Board as an OHDSI network study (IRB# pending).
Department of Veterans Affairs (VA)	Use of the VA EHR data source was approved by the Department of Veterans Affairs Central Institutional Review Board and was determined to meet the criteria for exemption under Exemption category4(3) and approved the request for Waiver of HIPAA Authorization (IRB# pending).

12 Management and Reporting of Adverse Events and Adverse Reactions

LEGEND-HtnStepCare uses coded data that already exist in electronic databases. In these types of databases, it is not usually possible to link (i.e., identify a potential causal association between) a particular product and medical event for any specific individual. Thus, the minimum criteria for reporting an adverse event (i.e., identifiable patient, identifiable reporter, a suspect product and event) are not available and adverse events are not reportable as individual adverse event reports. The study results will be assessed for medically important findings.

13 Plans for Disseminating and Communicating Study Results

Open science aims to make scientific research, including its data process and software, and its dissemination, through publication and presentation, accessible to all levels of an inquiring society, amateur or professional [181] and is a governing principle of LEGEND-HtnStepCare. Open science delivers reproducible, transparent and reliable evidence. All aspects of LEGEND-HtnStepCare (except private patient data) will be open and we will actively encourage other interested researchers, clinicians and patients to participate. This differs fundamentally from traditional studies that rarely open their analytic tools or share all result artifacts, and inform the community about hard-to-verify conclusions at completion.

13.1 Transparent and re-usable research tools

We will publicly register this protocol and announce its availability for feedback from stakeholders, the OHDSI community and within clinical professional societies. This protocol will link to open source code for all steps to generating diagnostics, effect estimates, figures and tables. Such transparency is possible because we will construct our studies on top of the OHDSI toolstack of open source software tools that are community developed and rigorously tested [178]. We will publicly host LEGEND-HtnStepCare source code at (https://github.com/ohdsi-studies/LegendHtnStepCare), allowing public contribution and review, and free re-use for anyone’s future research.

13.3 Scientific meetings and publications

We will deliver multiple presentations annually at scientific venues including the annual meetings of the American College of Cardiology, American Heart Association and American Medical Informatics Association. We will also prepare multiple scientific publications for clinical, informatics and statistical journals.

13.4 General public

We believe in sharing our findings that will guide clinical care with the general public. LEGEND-HtnStepCare will use social-media (e.g., X and LinkedIn) to facilitate this. With dedicated support from the OHDSI communications specialist, we will deliver regular press releases at key project stages, distributed via the extensive media networks of Yale, UCLA, and Columbia.

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Appendix

A Exposure Cohort Definitions

A.1 Class-vs-Class Exposure (First ACEI adding Thiazide) Cohort

A.1.1 Cohort Entry Events

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are >= 18 years old. Limit cohort entry events to the earliest event per person.

A.1.2 Additional Inclusion Criteria

I. rule1

Entry events having at least 1 drug exposure of ‘First agent’, starting anytime up to 30 days before cohort entry start date.

II. rule2

Entry events having at least 1 condition occurrence of ‘Hypertension’, starting anytime on or before cohort entry start date.

III. rule3

Entry events having exactly 1 distinct standard concepts from drug exposure of ‘Antihypertensives’, starting anytime prior to cohort entry start date.

IV. rule4

Entry events having no drug exposures of ‘Other agents’, starting between 0 days before and 180 days after cohort entry start date.

V. rule5

Entry events having no condition occurrences of ‘Previous CV events including acute MI, stroke, HF’, starting anytime prior to cohort entry start date.

A.1.3 Cohort Exit

The cohort end date will be based on a continuous exposure to ‘Second agent’: allowing 30 days between exposures, adding 30 days after exposure ends, and using days supply and exposure end date for exposure duration.

A.1.4 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

A.1.5 Concept: Second agent

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
1307046	metoprolol	6918	RxNorm	NO	YES	NO
1313200	nadolol	7226	RxNorm	NO	YES	NO
1314002	atenolol	1202	RxNorm	NO	YES	NO
1314577	nebivolol	31555	RxNorm	NO	YES	NO
1319998	acebutolol	149	RxNorm	NO	YES	NO
1322081	betaxolol	1520	RxNorm	NO	YES	NO
1327978	penbutolol	7973	RxNorm	NO	YES	NO
1338005	bisoprolol	19484	RxNorm	NO	YES	NO
1345858	pindolol	8332	RxNorm	NO	YES	NO
1346823	carvedilol	20352	RxNorm	NO	YES	NO
1353766	propranolol	8787	RxNorm	NO	YES	NO
1386957	labetalol	6185	RxNorm	NO	YES	NO

A.1.6 Concept: First agent

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
1308216	lisinopril	29046	RxNorm	NO	YES	NO
1310756	moexipril	30131	RxNorm	NO	YES	NO
1331235	quinapril	35208	RxNorm	NO	YES	NO
1334456	ramipril	35296	RxNorm	NO	YES	NO
1335471	benazepril	18867	RxNorm	NO	YES	NO
1340128	captopril	1998	RxNorm	NO	YES	NO
1341927	enalapril	3827	RxNorm	NO	YES	NO
1342439	trandolapril	38454	RxNorm	NO	YES	NO
1363749	fosinopril	50166	RxNorm	NO	YES	NO
1373225	perindopril	54552	RxNorm	NO	YES	NO
1510704	amlodipine / celecoxib Oral Product	2047711	RxNorm	YES	YES	NO
1510705	amlodipine / celecoxib Pill	2047712	RxNorm	YES	YES	NO
2064627	amlodipine / chlorthalidone / telmisartan Oral Tablet	OMOP4965915	RxNorm Extension	YES	YES	NO
21035025	Amiloride / Furosemide Oral Solution	OMOP402978	RxNorm Extension	YES	YES	NO
21052206	Chlorothiazide / Spironolactone Oral Solution	OMOP358547	RxNorm Extension	YES	YES	NO
21071954	Chlorothiazide / Spironolactone Oral Capsule	OMOP358549	RxNorm Extension	YES	YES	NO
21071955	Chlorothiazide / Spironolactone Injectable Solution	OMOP358550	RxNorm Extension	YES	YES	NO
21130571	Chlorothiazide / Spironolactone Oral Suspension	OMOP358548	RxNorm Extension	YES	YES	NO
21132694	Atenolol / Chlorthalidone Oral Solution	OMOP395909	RxNorm Extension	YES	YES	NO
21152528	Atenolol / Chlorthalidone Oral Suspension	OMOP395911	RxNorm Extension	YES	YES	NO
21152932	Amiloride / Furosemide Oral Suspension	OMOP402980	RxNorm Extension	YES	YES	NO
35146103	irbesartan / Trichlormethiazide Oral Tablet	OMOP4803186	RxNorm Extension	YES	YES	NO
35150194	Amlodipine / irbesartan Oral Tablet	OMOP4807246	RxNorm Extension	YES	YES	NO
35406763	Amlodipine / Indapamide / Perindopril Delayed Release Oral Tablet	OMOP1140348	RxNorm Extension	YES	YES	NO
35408893	Bisoprolol / Perindopril Delayed Release Oral Tablet	OMOP1142478	RxNorm Extension	YES	YES	NO
36212160	betaxolol / pilocarpine Ophthalmic Product	1153805	RxNorm	YES	YES	NO
36212261	captopril / hydrochlorothiazide Oral Product	1155750	RxNorm	YES	YES	NO
36212262	captopril / hydrochlorothiazide Pill	1155751	RxNorm	YES	YES	NO
36212293	chlorthalidone / clonidine Oral Product	1155783	RxNorm	YES	YES	NO
36212294	chlorthalidone / clonidine Pill	1155784	RxNorm	YES	YES	NO
36212295	chlorthalidone / hydralazine / oxprenolol Oral Product	1155785	RxNorm	YES	YES	NO
36212296	chlorthalidone / hydralazine / oxprenolol Pill	1155786	RxNorm	YES	YES	NO
36212297	chlorthalidone / metoprolol Oral Product	1155787	RxNorm	YES	YES	NO
36212298	chlorthalidone / metoprolol Pill	1155788	RxNorm	YES	YES	NO
36212299	chlorthalidone / oxprenolol Oral Product	1155789	RxNorm	YES	YES	NO
36212300	chlorthalidone / oxprenolol Pill	1155790	RxNorm	YES	YES	NO
36212301	chlorthalidone / reserpine Oral Product	1155791	RxNorm	YES	YES	NO
36212302	chlorthalidone / reserpine Pill	1155792	RxNorm	YES	YES	NO
36212303	chlorthalidone / triamterene Oral Product	1155793	RxNorm	YES	YES	NO
36212304	chlorthalidone / triamterene Pill	1155794	RxNorm	YES	YES	NO
36212400	chlorothiazide / methyldopa Oral Product	1153863	RxNorm	YES	YES	NO
36212401	chlorothiazide / methyldopa Pill	1153864	RxNorm	YES	YES	NO
36212440	clopamide / pindolol Oral Product	1153903	RxNorm	YES	YES	NO
36212441	clopamide / pindolol Pill	1153904	RxNorm	YES	YES	NO
36213274	bendroflumethiazide / clonidine Oral Product	1156019	RxNorm	YES	YES	NO
36213275	bendroflumethiazide / clonidine Pill	1156020	RxNorm	YES	YES	NO
36213278	bendroflumethiazide / nadolol Oral Product	1156023	RxNorm	YES	YES	NO
36213279	bendroflumethiazide / nadolol Pill	1156024	RxNorm	YES	YES	NO
36214315	indapamide / perindopril Oral Product	1156300	RxNorm	YES	YES	NO
36214316	indapamide / perindopril Pill	1156301	RxNorm	YES	YES	NO
36214477	atenolol / bendroflumethiazide Oral Product	1154366	RxNorm	YES	YES	NO
36214478	atenolol / bendroflumethiazide Pill	1154367	RxNorm	YES	YES	NO
36214479	atenolol / chlorthalidone / hydralazine Oral Product	1154368	RxNorm	YES	YES	NO
36214480	atenolol / chlorthalidone / hydralazine Pill	1154369	RxNorm	YES	YES	NO
36214481	atenolol / chlorthalidone Oral Product	1154370	RxNorm	YES	YES	NO
36214482	atenolol / chlorthalidone Pill	1154371	RxNorm	YES	YES	NO
36214483	atenolol / nifedipine Oral Product	1154374	RxNorm	YES	YES	NO
36214484	atenolol / nifedipine Pill	1154375	RxNorm	YES	YES	NO
36215127	althiazide / spironolactone Oral Product	1156535	RxNorm	YES	YES	NO
36215128	althiazide / spironolactone Pill	1156536	RxNorm	YES	YES	NO
36215209	dehydrosanol / triamterene Oral Product	1157731	RxNorm	YES	YES	NO
36215210	dehydrosanol / triamterene Pill	1157732	RxNorm	YES	YES	NO
36215223	deserpidine / hydrochlorothiazide Oral Product	1157745	RxNorm	YES	YES	NO
36215224	deserpidine / hydrochlorothiazide Pill	1157746	RxNorm	YES	YES	NO
36215393	candesartan / hydrochlorothiazide Oral Product	1156609	RxNorm	YES	YES	NO
36215394	candesartan / hydrochlorothiazide Pill	1156610	RxNorm	YES	YES	NO
36215416	cyclothiazide / triamterene Oral Product	1156637	RxNorm	YES	YES	NO
36215417	cyclothiazide / triamterene Pill	1156638	RxNorm	YES	YES	NO
36215809	bisoprolol / hydrochlorothiazide Oral Product	1154704	RxNorm	YES	YES	NO
36215810	bisoprolol / hydrochlorothiazide Pill	1154705	RxNorm	YES	YES	NO
36216030	dihydralazine / hydrochlorothiazide / reserpine Oral Product	1151524	RxNorm	YES	YES	NO
36216031	dihydralazine / hydrochlorothiazide / reserpine Pill	1151525	RxNorm	YES	YES	NO
36216034	dihydralazine / propranolol Oral Product	1151528	RxNorm	YES	YES	NO
36216035	dihydralazine / propranolol Pill	1151529	RxNorm	YES	YES	NO
36216161	amiloride / atenolol / hydrochlorothiazide Oral Product	1151590	RxNorm	YES	YES	NO
36216162	amiloride / atenolol / hydrochlorothiazide Pill	1151591	RxNorm	YES	YES	NO
36216163	amiloride / bendroflumethiazide Oral Product	1151592	RxNorm	YES	YES	NO
36216164	amiloride / bendroflumethiazide Pill	1151593	RxNorm	YES	YES	NO
36216165	amiloride / bumetanide Oral Product	1151594	RxNorm	YES	YES	NO
36216166	amiloride / bumetanide Pill	1151595	RxNorm	YES	YES	NO
36216167	amiloride / cyclopenthiazide Oral Product	1151596	RxNorm	YES	YES	NO
36216168	amiloride / cyclopenthiazide Pill	1151597	RxNorm	YES	YES	NO
36216169	amiloride / furosemide / indapamide Oral Product	1151598	RxNorm	YES	YES	NO
36216170	amiloride / furosemide / indapamide Pill	1151599	RxNorm	YES	YES	NO
36216171	amiloride / furosemide Oral Product	1151600	RxNorm	YES	YES	NO
36216172	amiloride / furosemide Pill	1151601	RxNorm	YES	YES	NO
36216173	amiloride / hydrochlorothiazide / methyldopa Oral Product	1151602	RxNorm	YES	YES	NO
36216174	amiloride / hydrochlorothiazide / methyldopa Pill	1151603	RxNorm	YES	YES	NO
36216175	amiloride / hydrochlorothiazide / timolol Oral Product	1151604	RxNorm	YES	YES	NO
36216176	amiloride / hydrochlorothiazide / timolol Pill	1151605	RxNorm	YES	YES	NO
36216246	amiloride / hydrochlorothiazide Oral Liquid Product	1151606	RxNorm	YES	YES	NO
36216247	amiloride / hydrochlorothiazide Oral Product	1151607	RxNorm	YES	YES	NO
36216248	amiloride / hydrochlorothiazide Pill	1151608	RxNorm	YES	YES	NO
36216249	amiloride / metolazone Oral Product	1151609	RxNorm	YES	YES	NO
36216250	amiloride / metolazone Pill	1151610	RxNorm	YES	YES	NO
36216251	amiloride / trichlormethiazide Oral Product	1151611	RxNorm	YES	YES	NO
36216252	amiloride / trichlormethiazide Pill	1151612	RxNorm	YES	YES	NO
36216551	cilazapril / hydrochlorothiazide Oral Product	1151778	RxNorm	YES	YES	NO
36216552	cilazapril / hydrochlorothiazide Pill	1151779	RxNorm	YES	YES	NO
36216725	diltiazem / enalapril Oral Product	1151883	RxNorm	YES	YES	NO
36216726	diltiazem / enalapril Pill	1151884	RxNorm	YES	YES	NO
36216727	diltiazem / hydrochlorothiazide Oral Product	1151885	RxNorm	YES	YES	NO
36216728	diltiazem / hydrochlorothiazide Pill	1151886	RxNorm	YES	YES	NO
36216899	acebutolol / hydrochlorothiazide Oral Product	1153651	RxNorm	YES	YES	NO
36216900	acebutolol / hydrochlorothiazide Pill	1153652	RxNorm	YES	YES	NO
36216901	acebutolol / mefruside Oral Product	1153653	RxNorm	YES	YES	NO
36216902	acebutolol / mefruside Pill	1153654	RxNorm	YES	YES	NO
36216903	acebutolol / nifedipine Oral Product	1153655	RxNorm	YES	YES	NO
36216904	acebutolol / nifedipine Pill	1153656	RxNorm	YES	YES	NO
36217137	clonidine / hydrochlorothiazide / triamterene Oral Product	1153380	RxNorm	YES	YES	NO
36217138	clonidine / hydrochlorothiazide / triamterene Pill	1153381	RxNorm	YES	YES	NO
36217139	clonidine / cyclothiazide Oral Product	1153382	RxNorm	YES	YES	NO
36217140	clonidine / cyclothiazide Pill	1153383	RxNorm	YES	YES	NO
36217664	bendroflumethiazide / propranolol Oral Product	1151296	RxNorm	YES	YES	NO
36217665	bendroflumethiazide / propranolol Pill	1151297	RxNorm	YES	YES	NO
36217670	bendroflumethiazide / spironolactone Oral Product	1151302	RxNorm	YES	YES	NO
36217671	bendroflumethiazide / spironolactone Pill	1151303	RxNorm	YES	YES	NO
36217708	amlodipine / hydrochlorothiazide / olmesartan Oral Product	1152277	RxNorm	YES	YES	NO
36217709	amlodipine / hydrochlorothiazide / olmesartan Pill	1152278	RxNorm	YES	YES	NO
36217710	amlodipine / hydrochlorothiazide / valsartan Oral Product	1152279	RxNorm	YES	YES	NO
36217711	amlodipine / hydrochlorothiazide / valsartan Pill	1152280	RxNorm	YES	YES	NO
36217712	amlodipine / atorvastatin Oral Product	1152281	RxNorm	YES	YES	NO
36217713	amlodipine / atorvastatin Pill	1152282	RxNorm	YES	YES	NO
36217714	amlodipine / benazepril Oral Product	1152283	RxNorm	YES	YES	NO
36217715	amlodipine / benazepril Pill	1152284	RxNorm	YES	YES	NO
36217716	amlodipine / olmesartan Oral Product	1152285	RxNorm	YES	YES	NO
36217717	amlodipine / olmesartan Pill	1152286	RxNorm	YES	YES	NO
36217718	amlodipine / telmisartan Oral Product	1152287	RxNorm	YES	YES	NO
36217719	amlodipine / telmisartan Pill	1152288	RxNorm	YES	YES	NO
36217720	amlodipine / valsartan Oral Product	1152289	RxNorm	YES	YES	NO
36217721	amlodipine / valsartan Pill	1152290	RxNorm	YES	YES	NO
36217842	bumetanide / potassium chloride Oral Product	1151343	RxNorm	YES	YES	NO
36217843	bumetanide / potassium chloride Pill	1151344	RxNorm	YES	YES	NO
36217844	bumetanide / potassium Oral Product	1151345	RxNorm	YES	YES	NO
36217845	bumetanide / potassium Pill	1151346	RxNorm	YES	YES	NO
36218311	hydrochlorothiazide / mepindolol Pill	1162774	RxNorm	YES	YES	NO
36218312	hydrochlorothiazide / moexipril Oral Product	1162775	RxNorm	YES	YES	NO
36218313	hydrochlorothiazide / moexipril Pill	1162776	RxNorm	YES	YES	NO
36218314	hydrochlorothiazide / olmesartan Oral Product	1162777	RxNorm	YES	YES	NO
36218315	hydrochlorothiazide / olmesartan Pill	1162778	RxNorm	YES	YES	NO
36218316	hydrochlorothiazide / quinapril Oral Product	1162779	RxNorm	YES	YES	NO
36218317	hydrochlorothiazide / quinapril Pill	1162780	RxNorm	YES	YES	NO
36218318	hydrochlorothiazide / telmisartan Oral Product	1162781	RxNorm	YES	YES	NO
36218319	hydrochlorothiazide / telmisartan Pill	1162782	RxNorm	YES	YES	NO
36218320	hydrochlorothiazide / valsartan Oral Product	1162783	RxNorm	YES	YES	NO
36218321	hydrochlorothiazide / valsartan Pill	1162784	RxNorm	YES	YES	NO
36218404	hydroflumethiazide / spironolactone Oral Product	1164019	RxNorm	YES	YES	NO
36218405	hydroflumethiazide / spironolactone Pill	1164020	RxNorm	YES	YES	NO
36218517	Hyzaar Oral Product	1166546	RxNorm	YES	YES	NO
36218518	Hyzaar Pill	1166549	RxNorm	YES	YES	NO
36218624	methyclothiazide / triamterene Oral Product	1162867	RxNorm	YES	YES	NO
36218625	methyclothiazide / triamterene Pill	1162868	RxNorm	YES	YES	NO
36219017	quinidine / verapamil Oral Product	1164182	RxNorm	YES	YES	NO
36219018	quinidine / verapamil Pill	1164183	RxNorm	YES	YES	NO
36219590	aliskiren / amlodipine / hydrochlorothiazide Oral Product	1164294	RxNorm	YES	YES	NO
36219628	buthiazide / spironolactone Oral Product	1164332	RxNorm	YES	YES	NO
36220155	piretanide / ramipril Oral Product	1163266	RxNorm	YES	YES	NO
36220156	piretanide / ramipril Pill	1163267	RxNorm	YES	YES	NO
36220835	hydroxyzine / labetalol Oral Product	1164636	RxNorm	YES	YES	NO
36220836	hydroxyzine / labetalol Pill	1164637	RxNorm	YES	YES	NO
36221077	metolazone / triamterene Oral Product	1163516	RxNorm	YES	YES	NO
36221078	metolazone / triamterene Pill	1163517	RxNorm	YES	YES	NO
36221081	metoprolol / nifedipine Oral Product	1163520	RxNorm	YES	YES	NO
36221082	metoprolol / nifedipine Pill	1163521	RxNorm	YES	YES	NO
36221405	penbutolol / piretanide Oral Product	1164756	RxNorm	YES	YES	NO
36221406	penbutolol / piretanide Pill	1164757	RxNorm	YES	YES	NO
36221767	aliskiren / amlodipine / hydrochlorothiazide Pill	1164880	RxNorm	YES	YES	NO
36221768	aliskiren / amlodipine Oral Product	1164881	RxNorm	YES	YES	NO
36221769	aliskiren / amlodipine Pill	1164882	RxNorm	YES	YES	NO
36221770	aliskiren / hydrochlorothiazide Oral Product	1164883	RxNorm	YES	YES	NO
36222006	aliskiren / hydrochlorothiazide Pill	1164884	RxNorm	YES	YES	NO
36222007	aliskiren / valsartan Oral Product	1164885	RxNorm	YES	YES	NO
36222008	aliskiren / valsartan Pill	1164886	RxNorm	YES	YES	NO
36222040	buthiazide / spironolactone Pill	1164919	RxNorm	YES	YES	NO
36223174	triamterene / xipamide Oral Product	1158232	RxNorm	YES	YES	NO
36223175	triamterene / xipamide Pill	1158233	RxNorm	YES	YES	NO
36223654	benzthiazide / triamterene Oral Product	1160544	RxNorm	YES	YES	NO
36223655	benzthiazide / triamterene Pill	1160545	RxNorm	YES	YES	NO
36224289	hydrochlorothiazide / labetalol Oral Product	1162122	RxNorm	YES	YES	NO
36224290	hydrochlorothiazide / labetalol Pill	1162123	RxNorm	YES	YES	NO
36224291	hydrochlorothiazide / lisinopril Oral Product	1162124	RxNorm	YES	YES	NO
36224292	hydrochlorothiazide / lisinopril Pill	1162125	RxNorm	YES	YES	NO
36224293	hydrochlorothiazide / losartan Oral Product	1162126	RxNorm	YES	YES	NO
36224294	hydrochlorothiazide / losartan Pill	1162127	RxNorm	YES	YES	NO
36224295	hydrochlorothiazide / magnesium chloride / methotrimeprazine Oral Product	1162128	RxNorm	YES	YES	NO
36224296	hydrochlorothiazide / magnesium chloride / methotrimeprazine Pill	1162129	RxNorm	YES	YES	NO
36224297	hydrochlorothiazide / methyldopa Oral Product	1162130	RxNorm	YES	YES	NO
36224298	hydrochlorothiazide / methyldopa Pill	1162131	RxNorm	YES	YES	NO
36224299	hydrochlorothiazide / metoprolol Oral Product	1162132	RxNorm	YES	YES	NO
36224300	hydrochlorothiazide / metoprolol Pill	1162133	RxNorm	YES	YES	NO
36224301	hydrochlorothiazide / pindolol Oral Product	1162134	RxNorm	YES	YES	NO
36224302	hydrochlorothiazide / pindolol Pill	1162135	RxNorm	YES	YES	NO
36224303	hydrochlorothiazide / potassium chloride Oral Product	1162136	RxNorm	YES	YES	NO
36224304	hydrochlorothiazide / potassium chloride Pill	1162137	RxNorm	YES	YES	NO
36224305	hydrochlorothiazide / propranolol Oral Product	1162138	RxNorm	YES	YES	NO
36224306	hydrochlorothiazide / propranolol Pill	1162139	RxNorm	YES	YES	NO
36224307	hydrochlorothiazide / ramipril Oral Product	1162140	RxNorm	YES	YES	NO
36224308	hydrochlorothiazide / ramipril Pill	1162141	RxNorm	YES	YES	NO
36224309	hydrochlorothiazide / reserpine Oral Product	1162142	RxNorm	YES	YES	NO
36224310	hydrochlorothiazide / reserpine Pill	1162143	RxNorm	YES	YES	NO
36224311	hydrochlorothiazide / sotalol Oral Product	1162144	RxNorm	YES	YES	NO
36224312	hydrochlorothiazide / sotalol Pill	1162145	RxNorm	YES	YES	NO
36224313	hydrochlorothiazide / spironolactone Oral Product	1162146	RxNorm	YES	YES	NO
36224314	hydrochlorothiazide / spironolactone Pill	1162147	RxNorm	YES	YES	NO
36224315	hydrochlorothiazide / timolol Oral Product	1162148	RxNorm	YES	YES	NO
36224316	hydrochlorothiazide / timolol Pill	1162149	RxNorm	YES	YES	NO
36224317	hydrochlorothiazide / triamterene / verapamil Oral Product	1162150	RxNorm	YES	YES	NO
36224318	hydrochlorothiazide / triamterene / verapamil Pill	1162151	RxNorm	YES	YES	NO
36224319	hydrochlorothiazide / triamterene Oral Product	1162152	RxNorm	YES	YES	NO
36224320	hydrochlorothiazide / triamterene Pill	1162153	RxNorm	YES	YES	NO
36224449	guanethidine / hydrochlorothiazide Oral Product	1159708	RxNorm	YES	YES	NO
36224450	guanethidine / hydrochlorothiazide Pill	1159709	RxNorm	YES	YES	NO
36224573	enalapril / felodipine Oral Product	1162647	RxNorm	YES	YES	NO
36224574	enalapril / felodipine Pill	1162648	RxNorm	YES	YES	NO
36224575	enalapril / hydrochlorothiazide Oral Product	1162649	RxNorm	YES	YES	NO
36224576	enalapril / hydrochlorothiazide Pill	1162650	RxNorm	YES	YES	NO
36224600	fosinopril / hydrochlorothiazide Oral Product	1162674	RxNorm	YES	YES	NO
36224601	fosinopril / hydrochlorothiazide Pill	1162675	RxNorm	YES	YES	NO
36224690	nicardipine / pyrithioxin Oral Product	1158667	RxNorm	YES	YES	NO
36224691	nicardipine / pyrithioxin Pill	1158668	RxNorm	YES	YES	NO
36224719	isosorbide dinitrate / verapamil Oral Product	1159751	RxNorm	YES	YES	NO
36224720	isosorbide dinitrate / verapamil Pill	1159752	RxNorm	YES	YES	NO
36225134	hydrochlorothiazide / verapamil Oral Product	1162154	RxNorm	YES	YES	NO
36225135	hydrochlorothiazide / verapamil Pill	1162155	RxNorm	YES	YES	NO
36225136	hydrochlorothiazide / irbesartan Oral Product	1162156	RxNorm	YES	YES	NO
36225137	hydrochlorothiazide / irbesartan Pill	1162157	RxNorm	YES	YES	NO
36225138	hydrochlorothiazide / mepindolol Oral Product	1162158	RxNorm	YES	YES	NO
36225434	furosemide / penbutolol Oral Product	1162702	RxNorm	YES	YES	NO
36225435	furosemide / penbutolol Pill	1162703	RxNorm	YES	YES	NO
36225436	furosemide / potassium chloride Oral Product	1162704	RxNorm	YES	YES	NO
36225437	furosemide / potassium chloride Pill	1162705	RxNorm	YES	YES	NO
36225438	furosemide / potassium Oral Product	1162706	RxNorm	YES	YES	NO
36225439	furosemide / potassium Pill	1162707	RxNorm	YES	YES	NO
36225440	furosemide / spironolactone Oral Product	1162708	RxNorm	YES	YES	NO
36225441	furosemide / spironolactone Pill	1162709	RxNorm	YES	YES	NO
36225442	furosemide / triamterene Oral Product	1162710	RxNorm	YES	YES	NO
36225443	furosemide / triamterene Pill	1162711	RxNorm	YES	YES	NO
36225488	trandolapril / verapamil Oral Product	1162756	RxNorm	YES	YES	NO
36225489	trandolapril / verapamil Pill	1162757	RxNorm	YES	YES	NO
36225635	benazepril / hydrochlorothiazide Oral Product	1160005	RxNorm	YES	YES	NO
36225636	benazepril / hydrochlorothiazide Pill	1160006	RxNorm	YES	YES	NO
36225790	eprosartan / hydrochlorothiazide Oral Product	1161918	RxNorm	YES	YES	NO
36225791	eprosartan / hydrochlorothiazide Pill	1161919	RxNorm	YES	YES	NO
36226052	ergoloid mesylates, USP / nifedipine Oral Product	1162494	RxNorm	YES	YES	NO
36226053	ergoloid mesylates, USP / nifedipine Pill	1162495	RxNorm	YES	YES	NO
36226137	felodipine / metoprolol Oral Product	1159024	RxNorm	YES	YES	NO
36226138	felodipine / metoprolol Pill	1159025	RxNorm	YES	YES	NO
36226139	felodipine / ramipril Oral Product	1159026	RxNorm	YES	YES	NO
36226140	felodipine / ramipril Pill	1159027	RxNorm	YES	YES	NO
36226883	pentaerythritol / propranolol Oral Product	1161389	RxNorm	YES	YES	NO
36226884	pentaerythritol / propranolol Pill	1161390	RxNorm	YES	YES	NO
36226979	mefruside / methyldopa Oral Product	1159202	RxNorm	YES	YES	NO
36226980	mefruside / methyldopa Pill	1159203	RxNorm	YES	YES	NO
36226981	mefruside / nifedipine Oral Product	1159204	RxNorm	YES	YES	NO
36226982	mefruside / nifedipine Pill	1159205	RxNorm	YES	YES	NO
36227399	polythiazide / prazosin Oral Product	1160457	RxNorm	YES	YES	NO
36227400	polythiazide / prazosin Pill	1160458	RxNorm	YES	YES	NO
36227481	hydralazine / hydrochlorothiazide / metoprolol Oral Product	1161545	RxNorm	YES	YES	NO
36227482	hydralazine / hydrochlorothiazide / metoprolol Pill	1161546	RxNorm	YES	YES	NO
36227483	hydralazine / hydrochlorothiazide / reserpine Oral Product	1161547	RxNorm	YES	YES	NO
36227484	hydralazine / hydrochlorothiazide / reserpine Pill	1161548	RxNorm	YES	YES	NO
36227485	hydralazine / hydrochlorothiazide Oral Product	1161549	RxNorm	YES	YES	NO
36227486	hydralazine / hydrochlorothiazide Pill	1161550	RxNorm	YES	YES	NO
36227487	hydralazine / isosorbide dinitrate Oral Product	1161551	RxNorm	YES	YES	NO
36227488	hydralazine / isosorbide dinitrate Pill	1161552	RxNorm	YES	YES	NO
36227489	hydralazine / reserpine Oral Product	1161553	RxNorm	YES	YES	NO
36227490	hydralazine / reserpine Pill	1161554	RxNorm	YES	YES	NO
36227929	Totaretic Oral Product	1178598	RxNorm	YES	YES	NO
36227930	Totaretic Pill	1178599	RxNorm	YES	YES	NO
36228123	Emcor LS Oral Product	1175298	RxNorm	YES	YES	NO
36228124	Emcor LS Pill	1175299	RxNorm	YES	YES	NO
36228734	Hydropres Oral Product	1175471	RxNorm	YES	YES	NO
36228735	Hydropres Pill	1175472	RxNorm	YES	YES	NO
36228737	Hydroserp Oral Product	1175476	RxNorm	YES	YES	NO
36228738	Hydroserp Pill	1175477	RxNorm	YES	YES	NO
36228739	Hydroserpine Oral Product	1175478	RxNorm	YES	YES	NO
36228740	Hydroserpine Pill	1175479	RxNorm	YES	YES	NO
36228868	Prinzide Oral Product	1178914	RxNorm	YES	YES	NO
36228869	Prinzide Pill	1178915	RxNorm	YES	YES	NO
36229025	Serpazide Oral Product	1180769	RxNorm	YES	YES	NO
36229026	Serpazide Pill	1180770	RxNorm	YES	YES	NO
36229027	Serpex Oral Product	1180771	RxNorm	YES	YES	NO
36229028	Serpex Pill	1180772	RxNorm	YES	YES	NO
36229222	Tarka Pill	1179047	RxNorm	YES	YES	NO
36229223	Tarka Oral Product	1179052	RxNorm	YES	YES	NO
36229579	Trandide Oral Product	1179179	RxNorm	YES	YES	NO
36229633	Tenoret Oral Product	1181453	RxNorm	YES	YES	NO
36230422	HHR Oral Product	1176066	RxNorm	YES	YES	NO
36230423	HHR Pill	1176067	RxNorm	YES	YES	NO
36230655	Teczem Oral Product	1180847	RxNorm	YES	YES	NO
36230656	Teczem Pill	1180848	RxNorm	YES	YES	NO
36230668	Tekamlo Oral Product	1180862	RxNorm	YES	YES	NO
36230669	Tekamlo Pill	1180865	RxNorm	YES	YES	NO
36230802	Tiamate Oral Product	1177910	RxNorm	YES	YES	NO
36231207	Tri-Hydroserpine Oral Product	1179709	RxNorm	YES	YES	NO
36231208	Tri-Hydroserpine Pill	1179710	RxNorm	YES	YES	NO
36231237	Mallopress Oral Product	1179744	RxNorm	YES	YES	NO
36231238	Mallopress Pill	1179745	RxNorm	YES	YES	NO
36231600	Lotrel Oral Product	1180906	RxNorm	YES	YES	NO
36231601	Lotrel Pill	1180909	RxNorm	YES	YES	NO
36231925	Moduret Oral Product	1181621	RxNorm	YES	YES	NO
36231926	Moduret Pill	1181622	RxNorm	YES	YES	NO
36231927	Moduretic Oral Product	1181623	RxNorm	YES	YES	NO
36231928	Moduretic Pill	1181624	RxNorm	YES	YES	NO
36232208	Regroton Oral Product	1180071	RxNorm	YES	YES	NO
36232209	Regroton Pill	1180072	RxNorm	YES	YES	NO
36232387	Hypolar Retard 20 Oral Product	1176719	RxNorm	YES	YES	NO
36232388	Hypolar Retard 20 Pill	1176720	RxNorm	YES	YES	NO
36232453	Tiamate Pill	1178487	RxNorm	YES	YES	NO
36232483	Timolide Oral Product	1178526	RxNorm	YES	YES	NO
36232484	Timolide Pill	1178527	RxNorm	YES	YES	NO
36232516	Ser-Ap-Es Oral Product	1180173	RxNorm	YES	YES	NO
36232517	Ser-Ap-Es Pill	1180174	RxNorm	YES	YES	NO
36232520	Serathide Oral Product	1180179	RxNorm	YES	YES	NO
36232521	Serathide Pill	1180180	RxNorm	YES	YES	NO
36232591	Marpres Oral Product	1181022	RxNorm	YES	YES	NO
36232592	Marpres Pill	1181023	RxNorm	YES	YES	NO
36233813	Inderide Oral Product	1172018	RxNorm	YES	YES	NO
36233814	Inderide Pill	1172027	RxNorm	YES	YES	NO
36234200	Atacand HCT Pill	1172182	RxNorm	YES	YES	NO
36234201	Atacand HCT Oral Product	1172183	RxNorm	YES	YES	NO
36234454	Benicar HCT Oral Product	1170817	RxNorm	YES	YES	NO
36234455	Benicar HCT Pill	1170818	RxNorm	YES	YES	NO
36234627	Labrocol Oral Product	1174956	RxNorm	YES	YES	NO
36234628	Labrocol Pill	1174957	RxNorm	YES	YES	NO
36235144	Demi-Regroton Oral Product	1172430	RxNorm	YES	YES	NO
36235145	Demi-Regroton Pill	1172431	RxNorm	YES	YES	NO
36236948	Aquazide H Oral Product	1170086	RxNorm	YES	YES	NO
36236949	Aquazide H Pill	1170087	RxNorm	YES	YES	NO
36237230	HydroDIURIL Oral Product	1174811	RxNorm	YES	YES	NO
36237231	HydroDIURIL Pill	1174812	RxNorm	YES	YES	NO
36237459	Diuretic Ap-Es Oral Product	1173148	RxNorm	YES	YES	NO
36237460	Diuretic Ap-Es Pill	1173149	RxNorm	YES	YES	NO
36237783	Exforge HCT Oral Product	1173249	RxNorm	YES	YES	NO
36237784	Exforge HCT Pill	1173250	RxNorm	YES	YES	NO
36237852	Hydrap-ES Oral Product	1174064	RxNorm	YES	YES	NO
36237853	Hydrap-ES Pill	1174065	RxNorm	YES	YES	NO
36237869	Hydro-Reserp Oral Product	1174092	RxNorm	YES	YES	NO
36237870	Hydro-Reserp Pill	1174093	RxNorm	YES	YES	NO
36238273	azilsartan / chlorthalidone Oral Product	1235140	RxNorm	YES	YES	NO
36238274	azilsartan / chlorthalidone Pill	1235141	RxNorm	YES	YES	NO
36238510	Tribenzor Pill	1182147	RxNorm	YES	YES	NO
36238819	Monopril-HCT Pill	1182235	RxNorm	YES	YES	NO
36238820	Monopril-HCT Oral Product	1182236	RxNorm	YES	YES	NO
36239006	Zestoretic Oral Product	1187277	RxNorm	YES	YES	NO
36239007	Zestoretic Pill	1187278	RxNorm	YES	YES	NO
36239102	Tribenzor Oral Product	1182686	RxNorm	YES	YES	NO
36239296	Valturna Oral Product	1187346	RxNorm	YES	YES	NO
36239297	Valturna Pill	1187347	RxNorm	YES	YES	NO
36239382	Maxzide Oral Product	1182741	RxNorm	YES	YES	NO
36239383	Maxzide Pill	1182742	RxNorm	YES	YES	NO
36239638	Ziac Pill	1187449	RxNorm	YES	YES	NO
36239639	Ziac Oral Product	1187450	RxNorm	YES	YES	NO
36239650	Zida-Co Oral Product	1187471	RxNorm	YES	YES	NO
36239651	Zida-Co Pill	1187472	RxNorm	YES	YES	NO
36239801	Mepranix Oral Product	1184390	RxNorm	YES	YES	NO
36239802	Mepranix Pill	1184391	RxNorm	YES	YES	NO
36239983	Vaseretic Oral Product	1187581	RxNorm	YES	YES	NO
36239984	Vaseretic Pill	1187582	RxNorm	YES	YES	NO
36240204	Quinaretic Oral Product	1185902	RxNorm	YES	YES	NO
36240205	Quinaretic Pill	1185903	RxNorm	YES	YES	NO
36241084	Unipres Oral Product	1186281	RxNorm	YES	YES	NO
36241085	Unipres Pill	1186282	RxNorm	YES	YES	NO
36241087	Uniretic Oral Product	1186288	RxNorm	YES	YES	NO
36241088	Uniretic Pill	1186289	RxNorm	YES	YES	NO
36241277	Teveten HCT Oral Product	1184922	RxNorm	YES	YES	NO
36241278	Teveten HCT Pill	1184923	RxNorm	YES	YES	NO
36242838	Twynsta Pill	1186904	RxNorm	YES	YES	NO
36242839	Twynsta Oral Product	1186905	RxNorm	YES	YES	NO
36243159	Uni Serp Oral Product	1187843	RxNorm	YES	YES	NO
36243160	Uni Serp Pill	1187844	RxNorm	YES	YES	NO
36243282	Tenoret Pill	1182012	RxNorm	YES	YES	NO
36243283	Tenoretic Oral Product	1182013	RxNorm	YES	YES	NO
36243284	Tenoretic Pill	1182014	RxNorm	YES	YES	NO
36247927	Tekturna HCT Oral Product	1430140	RxNorm	YES	YES	NO
36247928	Tekturna HCT Pill	1430141	RxNorm	YES	YES	NO
36248677	sacubitril / valsartan Oral Product	1656336	RxNorm	YES	YES	NO
36248678	sacubitril / valsartan Pill	1656337	RxNorm	YES	YES	NO
36248703	amlodipine / perindopril Oral Product	1600713	RxNorm	YES	YES	NO
36248704	amlodipine / perindopril Pill	1600714	RxNorm	YES	YES	NO
36248705	Prestalia Oral Product	1600720	RxNorm	YES	YES	NO
36248706	Prestalia Pill	1600721	RxNorm	YES	YES	NO
36250179	nebivolol / valsartan Oral Product	1798277	RxNorm	YES	YES	NO
36250180	nebivolol / valsartan Pill	1798278	RxNorm	YES	YES	NO
36259265	Amlodipine / Indapamide / Perindopril Oral Tablet	OMOP3110140	RxNorm Extension	YES	YES	NO
36264366	Hydrochlorothiazide / Metoprolol Extended Release Oral Capsule	OMOP3115241	RxNorm Extension	YES	YES	NO
36264394	Bisoprolol / Hydrochlorothiazide Oral Capsule	OMOP3115269	RxNorm Extension	YES	YES	NO
36266935	Bisoprolol / Perindopril Oral Tablet	OMOP3117810	RxNorm Extension	YES	YES	NO
36269479	Hydrochlorothiazide / Losartan Oral Capsule	OMOP3120354	RxNorm Extension	YES	YES	NO
36272027	Hydrochlorothiazide / nebivolol Oral Tablet	OMOP3122902	RxNorm Extension	YES	YES	NO
36272030	Felodipine / Ramipril Extended Release Oral Capsule	OMOP3122905	RxNorm Extension	YES	YES	NO
36274581	Felodipine / Metoprolol Extended Release Oral Capsule	OMOP3125456	RxNorm Extension	YES	YES	NO
36274595	Chlorthalidone / Metoprolol Extended Release Oral Capsule	OMOP3125470	RxNorm Extension	YES	YES	NO
36784817	Bisoprolol / Hydrochlorothiazide Extended Release Oral Tablet	OMOP4773102	RxNorm Extension	YES	YES	NO
36786066	Cilazapril / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP4774342	RxNorm Extension	YES	YES	NO
36787123	Amlodipine / Hydrochlorothiazide / olmesartan Delayed Release Oral Tablet	OMOP4775385	RxNorm Extension	YES	YES	NO
36787465	eprosartan / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP4775731	RxNorm Extension	YES	YES	NO
36881813	Chlorthalidone / Metoprolol Delayed Release Oral Tablet	OMOP993857	RxNorm Extension	YES	YES	NO
36889540	Chlorthalidone / Oxprenolol Delayed Release Oral Tablet	OMOP1004099	RxNorm Extension	YES	YES	NO
40003426	acebutolol / nifedipine Oral Tablet	446671	RxNorm	YES	YES	NO
40007368	amiloride / atenolol / hydrochlorothiazide Oral Capsule	379257	RxNorm	YES	YES	NO
40007369	amiloride / atenolol / hydrochlorothiazide Oral Tablet	437781	RxNorm	YES	YES	NO
40007373	amiloride / furosemide / indapamide Oral Tablet	437571	RxNorm	YES	YES	NO
40007374	amiloride / furosemide Oral Tablet	370847	RxNorm	YES	YES	NO
40007377	amiloride / hydrochlorothiazide / methyldopa Oral Tablet	446454	RxNorm	YES	YES	NO
40007378	amiloride / hydrochlorothiazide / timolol Oral Tablet	379256	RxNorm	YES	YES	NO
40007379	amiloride / hydrochlorothiazide Oral Solution	370848	RxNorm	YES	YES	NO
40007380	amiloride / hydrochlorothiazide Oral Tablet	370638	RxNorm	YES	YES	NO
40010558	atenolol / bendroflumethiazide Oral Capsule	385565	RxNorm	YES	YES	NO
40010559	atenolol / chlorthalidone / hydralazine Oral Tablet	440424	RxNorm	YES	YES	NO
40010560	atenolol / chlorthalidone Oral Capsule	370958	RxNorm	YES	YES	NO
40010561	atenolol / chlorthalidone Oral Tablet	370620	RxNorm	YES	YES	NO
40010567	atenolol / nifedipine Extended Release Oral Capsule	393276	RxNorm	YES	YES	NO
40010568	atenolol / nifedipine Oral Capsule	370961	RxNorm	YES	YES	NO
40010569	atenolol / nifedipine Oral Tablet	376172	RxNorm	YES	YES	NO
40011854	bendroflumethiazide / propranolol Extended Release Oral Capsule	373656	RxNorm	YES	YES	NO
40011855	bendroflumethiazide / propranolol Oral Capsule	373655	RxNorm	YES	YES	NO
40011856	bendroflumethiazide / propranolol Oral Tablet	373657	RxNorm	YES	YES	NO
40011860	bendroflumethiazide / timolol Oral Tablet	374136	RxNorm	YES	YES	NO
40015092	bisoprolol / hydrochlorothiazide Oral Tablet	371103	RxNorm	YES	YES	NO
40020436	chlorothiazide / methyldopa Oral Tablet [Aldoclor]	368245	RxNorm	YES	YES	NO
40026132	clonidine / hydrochlorothiazide / triamterene Oral Tablet	438743	RxNorm	YES	YES	NO
40027598	cilazapril / hydrochlorothiazide Oral Tablet	371507	RxNorm	YES	YES	NO
40028109	cyclopenthiazide / oxprenolol Extended Release Oral Tablet	373186	RxNorm	YES	YES	NO
40028110	cyclopenthiazide / oxprenolol Oral Tablet	373185	RxNorm	YES	YES	NO
40030840	chlorthalidone / hydralazine / oxprenolol Oral Tablet	440427	RxNorm	YES	YES	NO
40030842	chlorthalidone / metoprolol Extended Release Oral Tablet	446468	RxNorm	YES	YES	NO
40030843	chlorthalidone / metoprolol Oral Tablet	379254	RxNorm	YES	YES	NO
40030844	chlorthalidone / oxprenolol Extended Release Oral Tablet	373182	RxNorm	YES	YES	NO
40030845	chlorthalidone / oxprenolol Oral Tablet	373181	RxNorm	YES	YES	NO
40033922	dihydralazine / propranolol Oral Tablet	439011	RxNorm	YES	YES	NO
40034892	diltiazem / hydrochlorothiazide Extended Release Oral Capsule	385943	RxNorm	YES	YES	NO
40037280	felodipine / metoprolol Extended Release Oral Tablet	439560	RxNorm	YES	YES	NO
40037281	felodipine / ramipril Oral Tablet	393440	RxNorm	YES	YES	NO
40039294	ergoloid mesylates, USP / nifedipine Oral Tablet	439288	RxNorm	YES	YES	NO
40039680	furosemide / spironolactone Oral Capsule	373944	RxNorm	YES	YES	NO
40039681	furosemide / spironolactone Oral Tablet	451932	RxNorm	YES	YES	NO
40039682	furosemide / triamterene Extended Release Oral Capsule	452294	RxNorm	YES	YES	NO
40039683	furosemide / triamterene Oral Tablet	374196	RxNorm	YES	YES	NO
40044449	hydralazine / hydrochlorothiazide / metoprolol Oral Tablet	440425	RxNorm	YES	YES	NO
40044821	hydrochlorothiazide / losartan Oral Tablet	372650	RxNorm	YES	YES	NO
40044824	hydrochlorothiazide / magnesium chloride / methotrimeprazine Oral Tablet	440593	RxNorm	YES	YES	NO
40044831	hydrochlorothiazide / metoprolol Extended Release Oral Tablet	372890	RxNorm	YES	YES	NO
40044832	hydrochlorothiazide / metoprolol Oral Tablet	372889	RxNorm	YES	YES	NO
40044834	hydrochlorothiazide / olmesartan Oral Tablet	406041	RxNorm	YES	YES	NO
40044837	hydrochlorothiazide / potassium chloride Oral Tablet	376241	RxNorm	YES	YES	NO
40044838	hydrochlorothiazide / propranolol Extended Release Oral Capsule	373650	RxNorm	YES	YES	NO
40044839	hydrochlorothiazide / propranolol Oral Tablet	373651	RxNorm	YES	YES	NO
40044851	hydrochlorothiazide / spironolactone Oral Tablet	370639	RxNorm	YES	YES	NO
40044854	hydrochlorothiazide / timolol Oral Tablet	374419	RxNorm	YES	YES	NO
40044856	hydrochlorothiazide / triamterene / verapamil Oral Tablet	452537	RxNorm	YES	YES	NO
40044857	hydrochlorothiazide / triamterene Oral Capsule	370640	RxNorm	YES	YES	NO
40045116	hydrochlorothiazide / triamterene Oral Tablet	374192	RxNorm	YES	YES	NO
40045118	hydrochlorothiazide / verapamil Extended Release Oral Capsule	452536	RxNorm	YES	YES	NO
40045119	hydrochlorothiazide / irbesartan Oral Tablet	370705	RxNorm	YES	YES	NO
40045121	hydrochlorothiazide / mepindolol Oral Tablet	446301	RxNorm	YES	YES	NO
40045124	hydrochlorothiazide / quinapril Oral Tablet	373732	RxNorm	YES	YES	NO
40045126	hydrochlorothiazide / telmisartan Oral Tablet	378921	RxNorm	YES	YES	NO
40045128	hydrochlorothiazide / valsartan Oral Tablet	374280	RxNorm	YES	YES	NO
40049453	indapamide / perindopril Oral Tablet	393357	RxNorm	YES	YES	NO
40054917	dehydrosanol / triamterene Oral Capsule	452289	RxNorm	YES	YES	NO
40054918	dehydrosanol / triamterene Oral Tablet	452285	RxNorm	YES	YES	NO
40059139	eprosartan / hydrochlorothiazide Oral Tablet	378735	RxNorm	YES	YES	NO
40060227	cyclothiazide / triamterene Oral Tablet	452292	RxNorm	YES	YES	NO
40061782	metoprolol / nifedipine Extended Release Oral Capsule	446677	RxNorm	YES	YES	NO
40065740	methyclothiazide / triamterene Oral Tablet	452299	RxNorm	YES	YES	NO
40085584	triamterene / xipamide Oral Tablet	452302	RxNorm	YES	YES	NO
40095410	candesartan / hydrochlorothiazide Oral Tablet	374934	RxNorm	YES	YES	NO
40096153	benazepril / hydrochlorothiazide Oral Tablet	371000	RxNorm	YES	YES	NO
40096806	benzthiazide / triamterene Oral Capsule	374195	RxNorm	YES	YES	NO
40099414	trandolapril / verapamil Extended Release Oral Capsule	379582	RxNorm	YES	YES	NO
40099416	trandolapril / verapamil Extended Release Oral Tablet	374178	RxNorm	YES	YES	NO
40137849	hydrochlorothiazide / methyldopa Oral Tablet [Aldoril]	688642	RxNorm	YES	YES	NO
40140541	amlodipine / valsartan Oral Tablet	722125	RxNorm	YES	YES	NO
40142669	amlodipine / olmesartan Oral Tablet	730860	RxNorm	YES	YES	NO
40147525	aliskiren / hydrochlorothiazide Oral Tablet	754717	RxNorm	YES	YES	NO
40160338	amlodipine / hydrochlorothiazide / valsartan Oral Tablet	848130	RxNorm	YES	YES	NO
40167838	amlodipine / telmisartan Oral Tablet	876513	RxNorm	YES	YES	NO
40224153	amlodipine / hydrochlorothiazide / olmesartan Oral Tablet	999966	RxNorm	YES	YES	NO
40232328	aliskiren / amlodipine / hydrochlorothiazide Oral Tablet	1050796	RxNorm	YES	YES	NO
40749849	Chlorothiazide / Spironolactone Oral Powder	OMOP4707410	RxNorm Extension	YES	YES	NO
40830512	Hydrochlorothiazide / Reserpine / Triamterene Oral Tablet	OMOP2028474	RxNorm Extension	YES	YES	NO
40830513	european olive pollen extract / Hydrochlorothiazide / Potassium Oral Tablet	OMOP2028475	RxNorm Extension	YES	YES	NO
40893011	Dihydralazine / Hydrochlorothiazide / Potassium / Reserpine Oral Tablet	OMOP2090973	RxNorm Extension	YES	YES	NO
40924218	Canrenoic Acid / Furosemide / Phosphoric acid Injectable Solution	OMOP2122180	RxNorm Extension	YES	YES	NO
40924457	Amiloride / Timolol Oral Tablet	OMOP2122419	RxNorm Extension	YES	YES	NO
40955187	Hydrochlorothiazide / Potassium / Rauwolfia preparation / rescinnamine / Reserpine / Vitamin A / Vitamin E Oral Tablet	OMOP2153149	RxNorm Extension	YES	YES	NO
40955683	Alprenolol / Hydrochlorothiazide Oral Tablet	OMOP2153645	RxNorm Extension	YES	YES	NO
40986248	Propranolol / Valeriana officinalis whole extract Oral Capsule	OMOP2184210	RxNorm Extension	YES	YES	NO
40986369	Hydrochlorothiazide / Propranolol / Triamterene Oral Capsule	OMOP2184331	RxNorm Extension	YES	YES	NO
40986688	Bunitrolol / Hydrochlorothiazide / Triamterene Extended Release Oral Capsule	OMOP2184650	RxNorm Extension	YES	YES	NO
41017227	trandolapril / Verapamil Oral Tablet	OMOP2215189	RxNorm Extension	YES	YES	NO
41048702	Hydrochlorothiazide / Oxprenolol Oral Tablet	OMOP2246664	RxNorm Extension	YES	YES	NO
41080575	Amlodipine / Losartan Oral Tablet	OMOP2278537	RxNorm Extension	YES	YES	NO
41111670	Canrenoic Acid / Furosemide Injectable Solution	OMOP2309632	RxNorm Extension	YES	YES	NO
41143011	Felodipine / Metoprolol Oral Tablet	OMOP2340973	RxNorm Extension	YES	YES	NO
41143341	dehydrosanol / Hesperidin / Thiamine / Triamterene Oral Tablet	OMOP2341303	RxNorm Extension	YES	YES	NO
41174430	Amlodipine / Bisoprolol Oral Tablet	OMOP2372392	RxNorm Extension	YES	YES	NO
41174481	Aesculus hippocastanum bark extract / Hydrochlorothiazide / Triamterene Oral Tablet	OMOP2372443	RxNorm Extension	YES	YES	NO
41205367	Propranolol / Spironolactone Oral Tablet	OMOP2403329	RxNorm Extension	YES	YES	NO
41205620	Dihydroergotoxine / Nifedipine Oral Tablet	OMOP2403582	RxNorm Extension	YES	YES	NO
41236870	Amlodipine / candesartan Oral Capsule	OMOP2434832	RxNorm Extension	YES	YES	NO
41237790	Mefruside / Methyldopa Oral Tablet [Sali Presinol]	OMOP2435752	RxNorm Extension	YES	YES	NO
41238954	buthiazide / Methyldopa Oral Tablet [Sembrina]	OMOP2436916	RxNorm Extension	YES	YES	NO
41267737	Bupranolol / dehydrosanol / Triamterene Oral Tablet	OMOP2465699	RxNorm Extension	YES	YES	NO
41298388	Furosemide / Reserpine Oral Tablet	OMOP2496350	RxNorm Extension	YES	YES	NO
41298962	6-(Diethylaminomethyl)Rutin / CRATAEGUS LAEVIGATA FRUIT / Hexamethonium Hydroxide / Hydrochlorothiazide / Potassium / Rauwolfia preparation / Reserpine Oral Tablet	OMOP2496924	RxNorm Extension	YES	YES	NO
41299800	Mefruside / Methyldopa / Reserpine Oral Tablet [Caprinol]	OMOP2497762	RxNorm Extension	YES	YES	NO
42479214	Felodipine / Ramipril Extended Release Oral Tablet	OMOP419678	RxNorm Extension	YES	YES	NO
42705336	azilsartan / chlorthalidone Oral Tablet	1235142	RxNorm	YES	YES	NO
42874880	Felodipine / Ramipril Delayed Release Oral Tablet	OMOP4871998	RxNorm Extension	YES	YES	NO
42875928	Amlodipine / Hydrochlorothiazide / Ramipril Oral Capsule	OMOP4873041	RxNorm Extension	YES	YES	NO
42938519	Amlodipine / Hydrochlorothiazide / telmisartan Oral Tablet	OMOP4665192	RxNorm Extension	YES	YES	NO
42948657	lercanidipine / valsartan Oral Tablet	OMOP4675247	RxNorm Extension	YES	YES	NO
42950872	Amlodipine / Chlorthalidone / Losartan Oral Tablet	OMOP4677445	RxNorm Extension	YES	YES	NO
42960011	Amlodipine / fimasartan potassium Oral Tablet	OMOP4686518	RxNorm Extension	YES	YES	NO
42960024	fimasartan potassium / Hydrochlorothiazide Oral Tablet	OMOP4686530	RxNorm Extension	YES	YES	NO
42972643	atorvastatin / irbesartan Oral Tablet	OMOP4699050	RxNorm Extension	YES	YES	NO
43022805	carvedilol / ivabradine Delayed Release Oral Tablet	OMOP4837934	RxNorm Extension	YES	YES	NO
43134832	Hydrochlorothiazide / Losartan Delayed Release Oral Tablet	OMOP447236	RxNorm Extension	YES	YES	NO
43156974	aliskiren / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP447297	RxNorm Extension	YES	YES	NO
43157075	Hydrochlorothiazide / quinapril Delayed Release Oral Tablet	OMOP448040	RxNorm Extension	YES	YES	NO
43166576	benazepril / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP485878	RxNorm Extension	YES	YES	NO
43167787	Hydrochlorothiazide / olmesartan Delayed Release Oral Tablet	OMOP446318	RxNorm Extension	YES	YES	NO
43178952	Hydrochlorothiazide / zofenopril Delayed Release Oral Tablet	OMOP447280	RxNorm Extension	YES	YES	NO
43188587	Atenolol / Chlorthalidone Delayed Release Oral Tablet	OMOP488010	RxNorm Extension	YES	YES	NO
43189757	Hydrochlorothiazide / irbesartan Delayed Release Oral Tablet	OMOP446394	RxNorm Extension	YES	YES	NO
43189944	Hydrochlorothiazide / nebivolol Delayed Release Oral Tablet	OMOP448113	RxNorm Extension	YES	YES	NO
43193525	Indapamide / Perindopril Delayed Release Oral Tablet	OMOP480217	RxNorm Extension	YES	YES	NO
43199873	Hydrochlorothiazide / valsartan Delayed Release Oral Tablet	OMOP510396	RxNorm Extension	YES	YES	NO
43199916	Amlodipine / Hydrochlorothiazide / valsartan Delayed Release Oral Tablet	OMOP514110	RxNorm Extension	YES	YES	NO
43203499	Amlodipine / Indapamide Extended Release Oral Tablet	OMOP470511	RxNorm Extension	YES	YES	NO
43205563	Enalapril / lercanidipine Delayed Release Oral Tablet	OMOP489591	RxNorm Extension	YES	YES	NO
43211738	Bisoprolol / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP447790	RxNorm Extension	YES	YES	NO
43260913	Enalapril / lercanidipine Oral Tablet	OMOP530577	RxNorm Extension	YES	YES	NO
43585468	ivabradine / Metoprolol Oral Tablet	OMOP954444	RxNorm Extension	YES	YES	NO
43599922	dehydrosanol / Triamterene Delayed Release Oral Tablet	OMOP778743	RxNorm Extension	YES	YES	NO
43636119	Hydrochlorothiazide / zofenopril Oral Tablet	OMOP789674	RxNorm Extension	YES	YES	NO
43672256	Hydrochlorothiazide / Propranolol / Triamterene Oral Tablet	OMOP781184	RxNorm Extension	YES	YES	NO
43677126	Amlodipine / Ramipril Oral Capsule	OMOP670769	RxNorm Extension	YES	YES	NO
43725912	Bendroflumethiazide / Hydralazine / Propranolol Oral Capsule	OMOP778561	RxNorm Extension	YES	YES	NO
43748731	Enalapril / Nitrendipine Oral Tablet	OMOP671132	RxNorm Extension	YES	YES	NO
43749671	Amlodipine / candesartan Oral Tablet	OMOP687193	RxNorm Extension	YES	YES	NO
43839612	Amlodipine / Lisinopril Oral Tablet	OMOP682928	RxNorm Extension	YES	YES	NO
44031088	Hydrochlorothiazide / Methyldopa Oral Tablet [Aldoril 25]	OMOP1025719	RxNorm Extension	YES	YES	NO
44031476	Chlorothiazide / Methyldopa Oral Tablet [Supres]	OMOP1026107	RxNorm Extension	YES	YES	NO
44057083	Hydrochlorothiazide / Methyldopa Oral Tablet [Pms-Dopazide]	OMOP1051714	RxNorm Extension	YES	YES	NO
44069972	Hydrochlorothiazide / Methyldopa Oral Tablet [Aldoril 15]	OMOP1064603	RxNorm Extension	YES	YES	NO
44082841	Hydrochlorothiazide / Methyldopa Oral Tablet [Novo-Doparil]	OMOP1077472	RxNorm Extension	YES	YES	NO
44095788	Hydrochlorothiazide / Methyldopa Oral Tablet [Apo Methazide]	OMOP1090419	RxNorm Extension	YES	YES	NO
45892980	amlodipine / perindopril Oral Tablet	1600715	RxNorm	YES	YES	NO

A.1.7 Concept: Hypertension

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
320128	Essential hypertension	59621000	SNOMED	NO	YES	NO
4034031	Benign essential hypertension complicating AND/OR reason for care during pregnancy	23717007	SNOMED	YES	YES	NO
4083723	Essential hypertension complicating AND/OR reason for care during childbirth	18416000	SNOMED	YES	YES	NO
4215640	Benign essential hypertension complicating AND/OR reason for care during childbirth	71874008	SNOMED	YES	YES	NO
4302591	Essential hypertension complicating AND/OR reason for care during pregnancy	78808002	SNOMED	YES	YES	NO

A.1.8 Concept: Antihypertensives

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
904542	triamterene	10763	RxNorm	NO	YES	NO
907013	metolazone	6916	RxNorm	NO	YES	NO
932745	bumetanide	1808	RxNorm	NO	YES	NO
942350	torsemide	38413	RxNorm	NO	YES	NO
956874	furosemide	4603	RxNorm	NO	YES	NO
970250	spironolactone	9997	RxNorm	NO	YES	NO
974166	hydrochlorothiazide	5487	RxNorm	NO	YES	NO
978555	indapamide	5764	RxNorm	NO	YES	NO
991382	amiloride	644	RxNorm	NO	YES	NO
1305447	methyldopa	6876	RxNorm	NO	YES	NO
1307046	metoprolol	6918	RxNorm	NO	YES	NO
1307863	verapamil	11170	RxNorm	NO	YES	NO
1308216	lisinopril	29046	RxNorm	NO	YES	NO
1308842	valsartan	69749	RxNorm	NO	YES	NO
1309068	minoxidil	6984	RxNorm	NO	YES	NO
1309799	eplerenone	298869	RxNorm	NO	YES	NO
1310756	moexipril	30131	RxNorm	NO	YES	NO
1313200	nadolol	7226	RxNorm	NO	YES	NO
1314002	atenolol	1202	RxNorm	NO	YES	NO
1314577	nebivolol	31555	RxNorm	NO	YES	NO
1317640	telmisartan	73494	RxNorm	NO	YES	NO
1317967	aliskiren	325646	RxNorm	NO	YES	NO
1318137	nicardipine	7396	RxNorm	NO	YES	NO
1318853	nifedipine	7417	RxNorm	NO	YES	NO
1319880	nisoldipine	7435	RxNorm	NO	YES	NO
1319998	acebutolol	149	RxNorm	NO	YES	NO
1322081	betaxolol	1520	RxNorm	NO	YES	NO
1326012	isradipine	33910	RxNorm	NO	YES	NO
1327978	penbutolol	7973	RxNorm	NO	YES	NO
1328165	diltiazem	3443	RxNorm	NO	YES	NO
1331235	quinapril	35208	RxNorm	NO	YES	NO
1332418	amlodipine	17767	RxNorm	NO	YES	NO
1334456	ramipril	35296	RxNorm	NO	YES	NO
1335471	benazepril	18867	RxNorm	NO	YES	NO
1338005	bisoprolol	19484	RxNorm	NO	YES	NO
1340128	captopril	1998	RxNorm	NO	YES	NO
1341238	terazosin	37798	RxNorm	NO	YES	NO
1341927	enalapril	3827	RxNorm	NO	YES	NO
1342439	trandolapril	38454	RxNorm	NO	YES	NO
1344965	guanfacine	40114	RxNorm	NO	YES	NO
1345858	pindolol	8332	RxNorm	NO	YES	NO
1346686	eprosartan	83515	RxNorm	NO	YES	NO
1346823	carvedilol	20352	RxNorm	NO	YES	NO
1347384	irbesartan	83818	RxNorm	NO	YES	NO
1350489	prazosin	8629	RxNorm	NO	YES	NO
1351557	candesartan	214354	RxNorm	NO	YES	NO
1353766	propranolol	8787	RxNorm	NO	YES	NO
1353776	felodipine	4316	RxNorm	NO	YES	NO
1363053	doxazosin	49276	RxNorm	NO	YES	NO
1363749	fosinopril	50166	RxNorm	NO	YES	NO
1367500	losartan	52175	RxNorm	NO	YES	NO
1373225	perindopril	54552	RxNorm	NO	YES	NO
1373928	hydralazine	5470	RxNorm	NO	YES	NO
1386957	labetalol	6185	RxNorm	NO	YES	NO
1395058	chlorthalidone	2409	RxNorm	NO	YES	NO
1398937	clonidine	2599	RxNorm	NO	YES	NO
40226742	olmesartan	321064	RxNorm	NO	YES	NO
40235485	azilsartan	1091643	RxNorm	NO	YES	NO

A.1.9 Concept: Other agents

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
904542	triamterene	10763	RxNorm	NO	YES	NO
907013	metolazone	6916	RxNorm	NO	YES	NO
932745	bumetanide	1808	RxNorm	NO	YES	NO
942350	torsemide	38413	RxNorm	NO	YES	NO
956874	furosemide	4603	RxNorm	NO	YES	NO
970250	spironolactone	9997	RxNorm	NO	YES	NO
974166	hydrochlorothiazide	5487	RxNorm	NO	YES	NO
978555	indapamide	5764	RxNorm	NO	YES	NO
991382	amiloride	644	RxNorm	NO	YES	NO
1305447	methyldopa	6876	RxNorm	NO	YES	NO
1307863	verapamil	11170	RxNorm	NO	YES	NO
1308842	valsartan	69749	RxNorm	NO	YES	NO
1309068	minoxidil	6984	RxNorm	NO	YES	NO
1309799	eplerenone	298869	RxNorm	NO	YES	NO
1317640	telmisartan	73494	RxNorm	NO	YES	NO
1317967	aliskiren	325646	RxNorm	NO	YES	NO
1318137	nicardipine	7396	RxNorm	NO	YES	NO
1318853	nifedipine	7417	RxNorm	NO	YES	NO
1319880	nisoldipine	7435	RxNorm	NO	YES	NO
1326012	isradipine	33910	RxNorm	NO	YES	NO
1328165	diltiazem	3443	RxNorm	NO	YES	NO
1332418	amlodipine	17767	RxNorm	NO	YES	NO
1341238	terazosin	37798	RxNorm	NO	YES	NO
1344965	guanfacine	40114	RxNorm	NO	YES	NO
1346686	eprosartan	83515	RxNorm	NO	YES	NO
1347384	irbesartan	83818	RxNorm	NO	YES	NO
1350489	prazosin	8629	RxNorm	NO	YES	NO
1351557	candesartan	214354	RxNorm	NO	YES	NO
1353776	felodipine	4316	RxNorm	NO	YES	NO
1363053	doxazosin	49276	RxNorm	NO	YES	NO
1367500	losartan	52175	RxNorm	NO	YES	NO
1373928	hydralazine	5470	RxNorm	NO	YES	NO
1395058	chlorthalidone	2409	RxNorm	NO	YES	NO
1398937	clonidine	2599	RxNorm	NO	YES	NO
40226742	olmesartan	321064	RxNorm	NO	YES	NO
40235485	azilsartan	1091643	RxNorm	NO	YES	NO
1308216	lisinopril	29046	RxNorm	YES	YES	NO
1310756	moexipril	30131	RxNorm	YES	YES	NO
1331235	quinapril	35208	RxNorm	YES	YES	NO
1334456	ramipril	35296	RxNorm	YES	YES	NO
1335471	benazepril	18867	RxNorm	YES	YES	NO
1340128	captopril	1998	RxNorm	YES	YES	NO
1341927	enalapril	3827	RxNorm	YES	YES	NO
1342439	trandolapril	38454	RxNorm	YES	YES	NO
1363749	fosinopril	50166	RxNorm	YES	YES	NO
1373225	perindopril	54552	RxNorm	YES	YES	NO
1307046	metoprolol	6918	RxNorm	YES	YES	NO
1313200	nadolol	7226	RxNorm	YES	YES	NO
1314002	atenolol	1202	RxNorm	YES	YES	NO
1314577	nebivolol	31555	RxNorm	YES	YES	NO
1319998	acebutolol	149	RxNorm	YES	YES	NO
1322081	betaxolol	1520	RxNorm	YES	YES	NO
1327978	penbutolol	7973	RxNorm	YES	YES	NO
1338005	bisoprolol	19484	RxNorm	YES	YES	NO
1345858	pindolol	8332	RxNorm	YES	YES	NO
1346823	carvedilol	20352	RxNorm	YES	YES	NO
1353766	propranolol	8787	RxNorm	YES	YES	NO
1386957	labetalol	6185	RxNorm	YES	YES	NO

A.1.10 Concept: Previous CV events including acute MI, stroke, HF

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
372924	Cerebral artery occlusion	20059004	SNOMED	NO	NO	NO
375557	Cerebral embolism	75543006	SNOMED	NO	NO	NO
376713	Cerebral hemorrhage	274100004	SNOMED	NO	NO	NO
432923	Subarachnoid hemorrhage	21454007	SNOMED	NO	NO	NO
439847	Intracranial hemorrhage	1386000	SNOMED	NO	NO	NO
441874	Cerebral thrombosis	71444005	SNOMED	NO	NO	NO
316139	Heart failure	84114007	SNOMED	NO	YES	NO
443454	Cerebral infarction	432504007	SNOMED	NO	YES	NO
4329847	Myocardial infarction	22298006	SNOMED	NO	YES	NO
314666	Old myocardial infarction	1755008	SNOMED	YES	YES	NO
315295	Congestive rheumatic heart failure	82523003	SNOMED	YES	YES	NO

A.2 Escalation Exit Criteria (On-treatment 2)

The person also exists the cohort when encountering any of the following events:

drug exposures of ‘Other agents’.

A.3 Heterogenity Study Inclusion Criteria

A.3.1 Young age subgroup

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are between 18 and 44 years old.

Limit cohort entry events to the earliest event per person.

A.3.2 Middle age subgroup

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are between 45 and 64 years old.

Limit cohort entry events to the earliest event per person.

A.3.3 Old age subgroup

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are >= 65 years old.

Limit cohort entry events to the earliest event per person.

A.3.4 Female subgroup

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are female >= 18 years old.

Limit cohort entry events to the earliest event per person.

A.3.5 Male subgroup

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are male >= 18 years old.

Limit cohort entry events to the earliest event per person.

A.3.6 Black or African American subgroup

rule6

Entry events with the following event criteria: race is: “black or african american” or “black”.

A.4 Drug-vs-Drug Exposure (First amlodipine adding acebutolol

) Cohort

A.4.1 Cohort Entry Events

People with continuous observation of 365 days before event may enter the cohort when observing any of the following:

drug exposure of ‘Second agent’ for the first time in the person’s history, who are >= 18 years old. Limit cohort entry events to the earliest event per person.

A.4.2 Additional Inclusion Criteria

I. rule1

Entry events having at least 1 drug exposure of ‘First agent’, starting anytime up to 30 days before cohort entry start date.

II. rule2

Entry events having at least 1 condition occurrence of ‘Hypertension’, starting anytime on or before cohort entry start date.

III. rule3

Entry events having exactly 1 distinct standard concepts from drug exposure of ‘Antihypertensives’, starting anytime prior to cohort entry start date.

IV. rule4

Entry events having no drug exposures of ‘Other agents’, starting between 0 days before and 180 days after cohort entry start date.

V. rule5

Entry events having no condition occurrences of ‘Previous CV events including acute MI, stroke, HF’, starting anytime prior to cohort entry start date.

A.4.3 Cohort Exit

A.4.4 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

A.4.5 Concept: Second agent

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
1319998	acebutolol	149	RxNorm	NO	YES	NO

A.4.6 Concept: First agent

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
1332418	amlodipine	17767	RxNorm	NO	YES	NO
1510704	amlodipine / celecoxib Oral Product	2047711	RxNorm	YES	YES	NO
1510705	amlodipine / celecoxib Pill	2047712	RxNorm	YES	YES	NO
2064627	amlodipine / chlorthalidone / telmisartan Oral Tablet	OMOP4965915	RxNorm Extension	YES	YES	NO
21035025	Amiloride / Furosemide Oral Solution	OMOP402978	RxNorm Extension	YES	YES	NO
21052206	Chlorothiazide / Spironolactone Oral Solution	OMOP358547	RxNorm Extension	YES	YES	NO
21071954	Chlorothiazide / Spironolactone Oral Capsule	OMOP358549	RxNorm Extension	YES	YES	NO
21071955	Chlorothiazide / Spironolactone Injectable Solution	OMOP358550	RxNorm Extension	YES	YES	NO
21130571	Chlorothiazide / Spironolactone Oral Suspension	OMOP358548	RxNorm Extension	YES	YES	NO
21132694	Atenolol / Chlorthalidone Oral Solution	OMOP395909	RxNorm Extension	YES	YES	NO
21152528	Atenolol / Chlorthalidone Oral Suspension	OMOP395911	RxNorm Extension	YES	YES	NO
21152932	Amiloride / Furosemide Oral Suspension	OMOP402980	RxNorm Extension	YES	YES	NO
35146103	irbesartan / Trichlormethiazide Oral Tablet	OMOP4803186	RxNorm Extension	YES	YES	NO
35150194	Amlodipine / irbesartan Oral Tablet	OMOP4807246	RxNorm Extension	YES	YES	NO
35406763	Amlodipine / Indapamide / Perindopril Delayed Release Oral Tablet	OMOP1140348	RxNorm Extension	YES	YES	NO
35408893	Bisoprolol / Perindopril Delayed Release Oral Tablet	OMOP1142478	RxNorm Extension	YES	YES	NO
36212160	betaxolol / pilocarpine Ophthalmic Product	1153805	RxNorm	YES	YES	NO
36212261	captopril / hydrochlorothiazide Oral Product	1155750	RxNorm	YES	YES	NO
36212262	captopril / hydrochlorothiazide Pill	1155751	RxNorm	YES	YES	NO
36212293	chlorthalidone / clonidine Oral Product	1155783	RxNorm	YES	YES	NO
36212294	chlorthalidone / clonidine Pill	1155784	RxNorm	YES	YES	NO
36212295	chlorthalidone / hydralazine / oxprenolol Oral Product	1155785	RxNorm	YES	YES	NO
36212296	chlorthalidone / hydralazine / oxprenolol Pill	1155786	RxNorm	YES	YES	NO
36212297	chlorthalidone / metoprolol Oral Product	1155787	RxNorm	YES	YES	NO
36212298	chlorthalidone / metoprolol Pill	1155788	RxNorm	YES	YES	NO
36212299	chlorthalidone / oxprenolol Oral Product	1155789	RxNorm	YES	YES	NO
36212300	chlorthalidone / oxprenolol Pill	1155790	RxNorm	YES	YES	NO
36212301	chlorthalidone / reserpine Oral Product	1155791	RxNorm	YES	YES	NO
36212302	chlorthalidone / reserpine Pill	1155792	RxNorm	YES	YES	NO
36212303	chlorthalidone / triamterene Oral Product	1155793	RxNorm	YES	YES	NO
36212304	chlorthalidone / triamterene Pill	1155794	RxNorm	YES	YES	NO
36212400	chlorothiazide / methyldopa Oral Product	1153863	RxNorm	YES	YES	NO
36212401	chlorothiazide / methyldopa Pill	1153864	RxNorm	YES	YES	NO
36212440	clopamide / pindolol Oral Product	1153903	RxNorm	YES	YES	NO
36212441	clopamide / pindolol Pill	1153904	RxNorm	YES	YES	NO
36213274	bendroflumethiazide / clonidine Oral Product	1156019	RxNorm	YES	YES	NO
36213275	bendroflumethiazide / clonidine Pill	1156020	RxNorm	YES	YES	NO
36213278	bendroflumethiazide / nadolol Oral Product	1156023	RxNorm	YES	YES	NO
36213279	bendroflumethiazide / nadolol Pill	1156024	RxNorm	YES	YES	NO
36214315	indapamide / perindopril Oral Product	1156300	RxNorm	YES	YES	NO
36214316	indapamide / perindopril Pill	1156301	RxNorm	YES	YES	NO
36214477	atenolol / bendroflumethiazide Oral Product	1154366	RxNorm	YES	YES	NO
36214478	atenolol / bendroflumethiazide Pill	1154367	RxNorm	YES	YES	NO
36214479	atenolol / chlorthalidone / hydralazine Oral Product	1154368	RxNorm	YES	YES	NO
36214480	atenolol / chlorthalidone / hydralazine Pill	1154369	RxNorm	YES	YES	NO
36214481	atenolol / chlorthalidone Oral Product	1154370	RxNorm	YES	YES	NO
36214482	atenolol / chlorthalidone Pill	1154371	RxNorm	YES	YES	NO
36214483	atenolol / nifedipine Oral Product	1154374	RxNorm	YES	YES	NO
36214484	atenolol / nifedipine Pill	1154375	RxNorm	YES	YES	NO
36215127	althiazide / spironolactone Oral Product	1156535	RxNorm	YES	YES	NO
36215128	althiazide / spironolactone Pill	1156536	RxNorm	YES	YES	NO
36215209	dehydrosanol / triamterene Oral Product	1157731	RxNorm	YES	YES	NO
36215210	dehydrosanol / triamterene Pill	1157732	RxNorm	YES	YES	NO
36215223	deserpidine / hydrochlorothiazide Oral Product	1157745	RxNorm	YES	YES	NO
36215224	deserpidine / hydrochlorothiazide Pill	1157746	RxNorm	YES	YES	NO
36215393	candesartan / hydrochlorothiazide Oral Product	1156609	RxNorm	YES	YES	NO
36215394	candesartan / hydrochlorothiazide Pill	1156610	RxNorm	YES	YES	NO
36215416	cyclothiazide / triamterene Oral Product	1156637	RxNorm	YES	YES	NO
36215417	cyclothiazide / triamterene Pill	1156638	RxNorm	YES	YES	NO
36215809	bisoprolol / hydrochlorothiazide Oral Product	1154704	RxNorm	YES	YES	NO
36215810	bisoprolol / hydrochlorothiazide Pill	1154705	RxNorm	YES	YES	NO
36216030	dihydralazine / hydrochlorothiazide / reserpine Oral Product	1151524	RxNorm	YES	YES	NO
36216031	dihydralazine / hydrochlorothiazide / reserpine Pill	1151525	RxNorm	YES	YES	NO
36216034	dihydralazine / propranolol Oral Product	1151528	RxNorm	YES	YES	NO
36216035	dihydralazine / propranolol Pill	1151529	RxNorm	YES	YES	NO
36216161	amiloride / atenolol / hydrochlorothiazide Oral Product	1151590	RxNorm	YES	YES	NO
36216162	amiloride / atenolol / hydrochlorothiazide Pill	1151591	RxNorm	YES	YES	NO
36216163	amiloride / bendroflumethiazide Oral Product	1151592	RxNorm	YES	YES	NO
36216164	amiloride / bendroflumethiazide Pill	1151593	RxNorm	YES	YES	NO
36216165	amiloride / bumetanide Oral Product	1151594	RxNorm	YES	YES	NO
36216166	amiloride / bumetanide Pill	1151595	RxNorm	YES	YES	NO
36216167	amiloride / cyclopenthiazide Oral Product	1151596	RxNorm	YES	YES	NO
36216168	amiloride / cyclopenthiazide Pill	1151597	RxNorm	YES	YES	NO
36216169	amiloride / furosemide / indapamide Oral Product	1151598	RxNorm	YES	YES	NO
36216170	amiloride / furosemide / indapamide Pill	1151599	RxNorm	YES	YES	NO
36216171	amiloride / furosemide Oral Product	1151600	RxNorm	YES	YES	NO
36216172	amiloride / furosemide Pill	1151601	RxNorm	YES	YES	NO
36216173	amiloride / hydrochlorothiazide / methyldopa Oral Product	1151602	RxNorm	YES	YES	NO
36216174	amiloride / hydrochlorothiazide / methyldopa Pill	1151603	RxNorm	YES	YES	NO
36216175	amiloride / hydrochlorothiazide / timolol Oral Product	1151604	RxNorm	YES	YES	NO
36216176	amiloride / hydrochlorothiazide / timolol Pill	1151605	RxNorm	YES	YES	NO
36216246	amiloride / hydrochlorothiazide Oral Liquid Product	1151606	RxNorm	YES	YES	NO
36216247	amiloride / hydrochlorothiazide Oral Product	1151607	RxNorm	YES	YES	NO
36216248	amiloride / hydrochlorothiazide Pill	1151608	RxNorm	YES	YES	NO
36216249	amiloride / metolazone Oral Product	1151609	RxNorm	YES	YES	NO
36216250	amiloride / metolazone Pill	1151610	RxNorm	YES	YES	NO
36216251	amiloride / trichlormethiazide Oral Product	1151611	RxNorm	YES	YES	NO
36216252	amiloride / trichlormethiazide Pill	1151612	RxNorm	YES	YES	NO
36216551	cilazapril / hydrochlorothiazide Oral Product	1151778	RxNorm	YES	YES	NO
36216552	cilazapril / hydrochlorothiazide Pill	1151779	RxNorm	YES	YES	NO
36216725	diltiazem / enalapril Oral Product	1151883	RxNorm	YES	YES	NO
36216726	diltiazem / enalapril Pill	1151884	RxNorm	YES	YES	NO
36216727	diltiazem / hydrochlorothiazide Oral Product	1151885	RxNorm	YES	YES	NO
36216728	diltiazem / hydrochlorothiazide Pill	1151886	RxNorm	YES	YES	NO
36216899	acebutolol / hydrochlorothiazide Oral Product	1153651	RxNorm	YES	YES	NO
36216900	acebutolol / hydrochlorothiazide Pill	1153652	RxNorm	YES	YES	NO
36216901	acebutolol / mefruside Oral Product	1153653	RxNorm	YES	YES	NO
36216902	acebutolol / mefruside Pill	1153654	RxNorm	YES	YES	NO
36216903	acebutolol / nifedipine Oral Product	1153655	RxNorm	YES	YES	NO
36216904	acebutolol / nifedipine Pill	1153656	RxNorm	YES	YES	NO
36217137	clonidine / hydrochlorothiazide / triamterene Oral Product	1153380	RxNorm	YES	YES	NO
36217138	clonidine / hydrochlorothiazide / triamterene Pill	1153381	RxNorm	YES	YES	NO
36217139	clonidine / cyclothiazide Oral Product	1153382	RxNorm	YES	YES	NO
36217140	clonidine / cyclothiazide Pill	1153383	RxNorm	YES	YES	NO
36217664	bendroflumethiazide / propranolol Oral Product	1151296	RxNorm	YES	YES	NO
36217665	bendroflumethiazide / propranolol Pill	1151297	RxNorm	YES	YES	NO
36217670	bendroflumethiazide / spironolactone Oral Product	1151302	RxNorm	YES	YES	NO
36217671	bendroflumethiazide / spironolactone Pill	1151303	RxNorm	YES	YES	NO
36217708	amlodipine / hydrochlorothiazide / olmesartan Oral Product	1152277	RxNorm	YES	YES	NO
36217709	amlodipine / hydrochlorothiazide / olmesartan Pill	1152278	RxNorm	YES	YES	NO
36217710	amlodipine / hydrochlorothiazide / valsartan Oral Product	1152279	RxNorm	YES	YES	NO
36217711	amlodipine / hydrochlorothiazide / valsartan Pill	1152280	RxNorm	YES	YES	NO
36217712	amlodipine / atorvastatin Oral Product	1152281	RxNorm	YES	YES	NO
36217713	amlodipine / atorvastatin Pill	1152282	RxNorm	YES	YES	NO
36217714	amlodipine / benazepril Oral Product	1152283	RxNorm	YES	YES	NO
36217715	amlodipine / benazepril Pill	1152284	RxNorm	YES	YES	NO
36217716	amlodipine / olmesartan Oral Product	1152285	RxNorm	YES	YES	NO
36217717	amlodipine / olmesartan Pill	1152286	RxNorm	YES	YES	NO
36217718	amlodipine / telmisartan Oral Product	1152287	RxNorm	YES	YES	NO
36217719	amlodipine / telmisartan Pill	1152288	RxNorm	YES	YES	NO
36217720	amlodipine / valsartan Oral Product	1152289	RxNorm	YES	YES	NO
36217721	amlodipine / valsartan Pill	1152290	RxNorm	YES	YES	NO
36217842	bumetanide / potassium chloride Oral Product	1151343	RxNorm	YES	YES	NO
36217843	bumetanide / potassium chloride Pill	1151344	RxNorm	YES	YES	NO
36217844	bumetanide / potassium Oral Product	1151345	RxNorm	YES	YES	NO
36217845	bumetanide / potassium Pill	1151346	RxNorm	YES	YES	NO
36218311	hydrochlorothiazide / mepindolol Pill	1162774	RxNorm	YES	YES	NO
36218312	hydrochlorothiazide / moexipril Oral Product	1162775	RxNorm	YES	YES	NO
36218313	hydrochlorothiazide / moexipril Pill	1162776	RxNorm	YES	YES	NO
36218314	hydrochlorothiazide / olmesartan Oral Product	1162777	RxNorm	YES	YES	NO
36218315	hydrochlorothiazide / olmesartan Pill	1162778	RxNorm	YES	YES	NO
36218316	hydrochlorothiazide / quinapril Oral Product	1162779	RxNorm	YES	YES	NO
36218317	hydrochlorothiazide / quinapril Pill	1162780	RxNorm	YES	YES	NO
36218318	hydrochlorothiazide / telmisartan Oral Product	1162781	RxNorm	YES	YES	NO
36218319	hydrochlorothiazide / telmisartan Pill	1162782	RxNorm	YES	YES	NO
36218320	hydrochlorothiazide / valsartan Oral Product	1162783	RxNorm	YES	YES	NO
36218321	hydrochlorothiazide / valsartan Pill	1162784	RxNorm	YES	YES	NO
36218404	hydroflumethiazide / spironolactone Oral Product	1164019	RxNorm	YES	YES	NO
36218405	hydroflumethiazide / spironolactone Pill	1164020	RxNorm	YES	YES	NO
36218517	Hyzaar Oral Product	1166546	RxNorm	YES	YES	NO
36218518	Hyzaar Pill	1166549	RxNorm	YES	YES	NO
36218624	methyclothiazide / triamterene Oral Product	1162867	RxNorm	YES	YES	NO
36218625	methyclothiazide / triamterene Pill	1162868	RxNorm	YES	YES	NO
36219017	quinidine / verapamil Oral Product	1164182	RxNorm	YES	YES	NO
36219018	quinidine / verapamil Pill	1164183	RxNorm	YES	YES	NO
36219590	aliskiren / amlodipine / hydrochlorothiazide Oral Product	1164294	RxNorm	YES	YES	NO
36219628	buthiazide / spironolactone Oral Product	1164332	RxNorm	YES	YES	NO
36220155	piretanide / ramipril Oral Product	1163266	RxNorm	YES	YES	NO
36220156	piretanide / ramipril Pill	1163267	RxNorm	YES	YES	NO
36220835	hydroxyzine / labetalol Oral Product	1164636	RxNorm	YES	YES	NO
36220836	hydroxyzine / labetalol Pill	1164637	RxNorm	YES	YES	NO
36221077	metolazone / triamterene Oral Product	1163516	RxNorm	YES	YES	NO
36221078	metolazone / triamterene Pill	1163517	RxNorm	YES	YES	NO
36221081	metoprolol / nifedipine Oral Product	1163520	RxNorm	YES	YES	NO
36221082	metoprolol / nifedipine Pill	1163521	RxNorm	YES	YES	NO
36221405	penbutolol / piretanide Oral Product	1164756	RxNorm	YES	YES	NO
36221406	penbutolol / piretanide Pill	1164757	RxNorm	YES	YES	NO
36221767	aliskiren / amlodipine / hydrochlorothiazide Pill	1164880	RxNorm	YES	YES	NO
36221768	aliskiren / amlodipine Oral Product	1164881	RxNorm	YES	YES	NO
36221769	aliskiren / amlodipine Pill	1164882	RxNorm	YES	YES	NO
36221770	aliskiren / hydrochlorothiazide Oral Product	1164883	RxNorm	YES	YES	NO
36222006	aliskiren / hydrochlorothiazide Pill	1164884	RxNorm	YES	YES	NO
36222007	aliskiren / valsartan Oral Product	1164885	RxNorm	YES	YES	NO
36222008	aliskiren / valsartan Pill	1164886	RxNorm	YES	YES	NO
36222040	buthiazide / spironolactone Pill	1164919	RxNorm	YES	YES	NO
36223174	triamterene / xipamide Oral Product	1158232	RxNorm	YES	YES	NO
36223175	triamterene / xipamide Pill	1158233	RxNorm	YES	YES	NO
36223654	benzthiazide / triamterene Oral Product	1160544	RxNorm	YES	YES	NO
36223655	benzthiazide / triamterene Pill	1160545	RxNorm	YES	YES	NO
36224289	hydrochlorothiazide / labetalol Oral Product	1162122	RxNorm	YES	YES	NO
36224290	hydrochlorothiazide / labetalol Pill	1162123	RxNorm	YES	YES	NO
36224291	hydrochlorothiazide / lisinopril Oral Product	1162124	RxNorm	YES	YES	NO
36224292	hydrochlorothiazide / lisinopril Pill	1162125	RxNorm	YES	YES	NO
36224293	hydrochlorothiazide / losartan Oral Product	1162126	RxNorm	YES	YES	NO
36224294	hydrochlorothiazide / losartan Pill	1162127	RxNorm	YES	YES	NO
36224295	hydrochlorothiazide / magnesium chloride / methotrimeprazine Oral Product	1162128	RxNorm	YES	YES	NO
36224296	hydrochlorothiazide / magnesium chloride / methotrimeprazine Pill	1162129	RxNorm	YES	YES	NO
36224297	hydrochlorothiazide / methyldopa Oral Product	1162130	RxNorm	YES	YES	NO
36224298	hydrochlorothiazide / methyldopa Pill	1162131	RxNorm	YES	YES	NO
36224299	hydrochlorothiazide / metoprolol Oral Product	1162132	RxNorm	YES	YES	NO
36224300	hydrochlorothiazide / metoprolol Pill	1162133	RxNorm	YES	YES	NO
36224301	hydrochlorothiazide / pindolol Oral Product	1162134	RxNorm	YES	YES	NO
36224302	hydrochlorothiazide / pindolol Pill	1162135	RxNorm	YES	YES	NO
36224303	hydrochlorothiazide / potassium chloride Oral Product	1162136	RxNorm	YES	YES	NO
36224304	hydrochlorothiazide / potassium chloride Pill	1162137	RxNorm	YES	YES	NO
36224305	hydrochlorothiazide / propranolol Oral Product	1162138	RxNorm	YES	YES	NO
36224306	hydrochlorothiazide / propranolol Pill	1162139	RxNorm	YES	YES	NO
36224307	hydrochlorothiazide / ramipril Oral Product	1162140	RxNorm	YES	YES	NO
36224308	hydrochlorothiazide / ramipril Pill	1162141	RxNorm	YES	YES	NO
36224309	hydrochlorothiazide / reserpine Oral Product	1162142	RxNorm	YES	YES	NO
36224310	hydrochlorothiazide / reserpine Pill	1162143	RxNorm	YES	YES	NO
36224311	hydrochlorothiazide / sotalol Oral Product	1162144	RxNorm	YES	YES	NO
36224312	hydrochlorothiazide / sotalol Pill	1162145	RxNorm	YES	YES	NO
36224313	hydrochlorothiazide / spironolactone Oral Product	1162146	RxNorm	YES	YES	NO
36224314	hydrochlorothiazide / spironolactone Pill	1162147	RxNorm	YES	YES	NO
36224315	hydrochlorothiazide / timolol Oral Product	1162148	RxNorm	YES	YES	NO
36224316	hydrochlorothiazide / timolol Pill	1162149	RxNorm	YES	YES	NO
36224317	hydrochlorothiazide / triamterene / verapamil Oral Product	1162150	RxNorm	YES	YES	NO
36224318	hydrochlorothiazide / triamterene / verapamil Pill	1162151	RxNorm	YES	YES	NO
36224319	hydrochlorothiazide / triamterene Oral Product	1162152	RxNorm	YES	YES	NO
36224320	hydrochlorothiazide / triamterene Pill	1162153	RxNorm	YES	YES	NO
36224449	guanethidine / hydrochlorothiazide Oral Product	1159708	RxNorm	YES	YES	NO
36224450	guanethidine / hydrochlorothiazide Pill	1159709	RxNorm	YES	YES	NO
36224573	enalapril / felodipine Oral Product	1162647	RxNorm	YES	YES	NO
36224574	enalapril / felodipine Pill	1162648	RxNorm	YES	YES	NO
36224575	enalapril / hydrochlorothiazide Oral Product	1162649	RxNorm	YES	YES	NO
36224576	enalapril / hydrochlorothiazide Pill	1162650	RxNorm	YES	YES	NO
36224600	fosinopril / hydrochlorothiazide Oral Product	1162674	RxNorm	YES	YES	NO
36224601	fosinopril / hydrochlorothiazide Pill	1162675	RxNorm	YES	YES	NO
36224690	nicardipine / pyrithioxin Oral Product	1158667	RxNorm	YES	YES	NO
36224691	nicardipine / pyrithioxin Pill	1158668	RxNorm	YES	YES	NO
36224719	isosorbide dinitrate / verapamil Oral Product	1159751	RxNorm	YES	YES	NO
36224720	isosorbide dinitrate / verapamil Pill	1159752	RxNorm	YES	YES	NO
36225134	hydrochlorothiazide / verapamil Oral Product	1162154	RxNorm	YES	YES	NO
36225135	hydrochlorothiazide / verapamil Pill	1162155	RxNorm	YES	YES	NO
36225136	hydrochlorothiazide / irbesartan Oral Product	1162156	RxNorm	YES	YES	NO
36225137	hydrochlorothiazide / irbesartan Pill	1162157	RxNorm	YES	YES	NO
36225138	hydrochlorothiazide / mepindolol Oral Product	1162158	RxNorm	YES	YES	NO
36225434	furosemide / penbutolol Oral Product	1162702	RxNorm	YES	YES	NO
36225435	furosemide / penbutolol Pill	1162703	RxNorm	YES	YES	NO
36225436	furosemide / potassium chloride Oral Product	1162704	RxNorm	YES	YES	NO
36225437	furosemide / potassium chloride Pill	1162705	RxNorm	YES	YES	NO
36225438	furosemide / potassium Oral Product	1162706	RxNorm	YES	YES	NO
36225439	furosemide / potassium Pill	1162707	RxNorm	YES	YES	NO
36225440	furosemide / spironolactone Oral Product	1162708	RxNorm	YES	YES	NO
36225441	furosemide / spironolactone Pill	1162709	RxNorm	YES	YES	NO
36225442	furosemide / triamterene Oral Product	1162710	RxNorm	YES	YES	NO
36225443	furosemide / triamterene Pill	1162711	RxNorm	YES	YES	NO
36225488	trandolapril / verapamil Oral Product	1162756	RxNorm	YES	YES	NO
36225489	trandolapril / verapamil Pill	1162757	RxNorm	YES	YES	NO
36225635	benazepril / hydrochlorothiazide Oral Product	1160005	RxNorm	YES	YES	NO
36225636	benazepril / hydrochlorothiazide Pill	1160006	RxNorm	YES	YES	NO
36225790	eprosartan / hydrochlorothiazide Oral Product	1161918	RxNorm	YES	YES	NO
36225791	eprosartan / hydrochlorothiazide Pill	1161919	RxNorm	YES	YES	NO
36226052	ergoloid mesylates, USP / nifedipine Oral Product	1162494	RxNorm	YES	YES	NO
36226053	ergoloid mesylates, USP / nifedipine Pill	1162495	RxNorm	YES	YES	NO
36226137	felodipine / metoprolol Oral Product	1159024	RxNorm	YES	YES	NO
36226138	felodipine / metoprolol Pill	1159025	RxNorm	YES	YES	NO
36226139	felodipine / ramipril Oral Product	1159026	RxNorm	YES	YES	NO
36226140	felodipine / ramipril Pill	1159027	RxNorm	YES	YES	NO
36226883	pentaerythritol / propranolol Oral Product	1161389	RxNorm	YES	YES	NO
36226884	pentaerythritol / propranolol Pill	1161390	RxNorm	YES	YES	NO
36226979	mefruside / methyldopa Oral Product	1159202	RxNorm	YES	YES	NO
36226980	mefruside / methyldopa Pill	1159203	RxNorm	YES	YES	NO
36226981	mefruside / nifedipine Oral Product	1159204	RxNorm	YES	YES	NO
36226982	mefruside / nifedipine Pill	1159205	RxNorm	YES	YES	NO
36227399	polythiazide / prazosin Oral Product	1160457	RxNorm	YES	YES	NO
36227400	polythiazide / prazosin Pill	1160458	RxNorm	YES	YES	NO
36227481	hydralazine / hydrochlorothiazide / metoprolol Oral Product	1161545	RxNorm	YES	YES	NO
36227482	hydralazine / hydrochlorothiazide / metoprolol Pill	1161546	RxNorm	YES	YES	NO
36227483	hydralazine / hydrochlorothiazide / reserpine Oral Product	1161547	RxNorm	YES	YES	NO
36227484	hydralazine / hydrochlorothiazide / reserpine Pill	1161548	RxNorm	YES	YES	NO
36227485	hydralazine / hydrochlorothiazide Oral Product	1161549	RxNorm	YES	YES	NO
36227486	hydralazine / hydrochlorothiazide Pill	1161550	RxNorm	YES	YES	NO
36227487	hydralazine / isosorbide dinitrate Oral Product	1161551	RxNorm	YES	YES	NO
36227488	hydralazine / isosorbide dinitrate Pill	1161552	RxNorm	YES	YES	NO
36227489	hydralazine / reserpine Oral Product	1161553	RxNorm	YES	YES	NO
36227490	hydralazine / reserpine Pill	1161554	RxNorm	YES	YES	NO
36227929	Totaretic Oral Product	1178598	RxNorm	YES	YES	NO
36227930	Totaretic Pill	1178599	RxNorm	YES	YES	NO
36228123	Emcor LS Oral Product	1175298	RxNorm	YES	YES	NO
36228124	Emcor LS Pill	1175299	RxNorm	YES	YES	NO
36228734	Hydropres Oral Product	1175471	RxNorm	YES	YES	NO
36228735	Hydropres Pill	1175472	RxNorm	YES	YES	NO
36228737	Hydroserp Oral Product	1175476	RxNorm	YES	YES	NO
36228738	Hydroserp Pill	1175477	RxNorm	YES	YES	NO
36228739	Hydroserpine Oral Product	1175478	RxNorm	YES	YES	NO
36228740	Hydroserpine Pill	1175479	RxNorm	YES	YES	NO
36228868	Prinzide Oral Product	1178914	RxNorm	YES	YES	NO
36228869	Prinzide Pill	1178915	RxNorm	YES	YES	NO
36229025	Serpazide Oral Product	1180769	RxNorm	YES	YES	NO
36229026	Serpazide Pill	1180770	RxNorm	YES	YES	NO
36229027	Serpex Oral Product	1180771	RxNorm	YES	YES	NO
36229028	Serpex Pill	1180772	RxNorm	YES	YES	NO
36229222	Tarka Pill	1179047	RxNorm	YES	YES	NO
36229223	Tarka Oral Product	1179052	RxNorm	YES	YES	NO
36229579	Trandide Oral Product	1179179	RxNorm	YES	YES	NO
36229633	Tenoret Oral Product	1181453	RxNorm	YES	YES	NO
36230422	HHR Oral Product	1176066	RxNorm	YES	YES	NO
36230423	HHR Pill	1176067	RxNorm	YES	YES	NO
36230655	Teczem Oral Product	1180847	RxNorm	YES	YES	NO
36230656	Teczem Pill	1180848	RxNorm	YES	YES	NO
36230668	Tekamlo Oral Product	1180862	RxNorm	YES	YES	NO
36230669	Tekamlo Pill	1180865	RxNorm	YES	YES	NO
36230802	Tiamate Oral Product	1177910	RxNorm	YES	YES	NO
36231207	Tri-Hydroserpine Oral Product	1179709	RxNorm	YES	YES	NO
36231208	Tri-Hydroserpine Pill	1179710	RxNorm	YES	YES	NO
36231237	Mallopress Oral Product	1179744	RxNorm	YES	YES	NO
36231238	Mallopress Pill	1179745	RxNorm	YES	YES	NO
36231600	Lotrel Oral Product	1180906	RxNorm	YES	YES	NO
36231601	Lotrel Pill	1180909	RxNorm	YES	YES	NO
36231925	Moduret Oral Product	1181621	RxNorm	YES	YES	NO
36231926	Moduret Pill	1181622	RxNorm	YES	YES	NO
36231927	Moduretic Oral Product	1181623	RxNorm	YES	YES	NO
36231928	Moduretic Pill	1181624	RxNorm	YES	YES	NO
36232208	Regroton Oral Product	1180071	RxNorm	YES	YES	NO
36232209	Regroton Pill	1180072	RxNorm	YES	YES	NO
36232387	Hypolar Retard 20 Oral Product	1176719	RxNorm	YES	YES	NO
36232388	Hypolar Retard 20 Pill	1176720	RxNorm	YES	YES	NO
36232453	Tiamate Pill	1178487	RxNorm	YES	YES	NO
36232483	Timolide Oral Product	1178526	RxNorm	YES	YES	NO
36232484	Timolide Pill	1178527	RxNorm	YES	YES	NO
36232516	Ser-Ap-Es Oral Product	1180173	RxNorm	YES	YES	NO
36232517	Ser-Ap-Es Pill	1180174	RxNorm	YES	YES	NO
36232520	Serathide Oral Product	1180179	RxNorm	YES	YES	NO
36232521	Serathide Pill	1180180	RxNorm	YES	YES	NO
36232591	Marpres Oral Product	1181022	RxNorm	YES	YES	NO
36232592	Marpres Pill	1181023	RxNorm	YES	YES	NO
36233813	Inderide Oral Product	1172018	RxNorm	YES	YES	NO
36233814	Inderide Pill	1172027	RxNorm	YES	YES	NO
36234200	Atacand HCT Pill	1172182	RxNorm	YES	YES	NO
36234201	Atacand HCT Oral Product	1172183	RxNorm	YES	YES	NO
36234454	Benicar HCT Oral Product	1170817	RxNorm	YES	YES	NO
36234455	Benicar HCT Pill	1170818	RxNorm	YES	YES	NO
36234627	Labrocol Oral Product	1174956	RxNorm	YES	YES	NO
36234628	Labrocol Pill	1174957	RxNorm	YES	YES	NO
36235144	Demi-Regroton Oral Product	1172430	RxNorm	YES	YES	NO
36235145	Demi-Regroton Pill	1172431	RxNorm	YES	YES	NO
36236948	Aquazide H Oral Product	1170086	RxNorm	YES	YES	NO
36236949	Aquazide H Pill	1170087	RxNorm	YES	YES	NO
36237230	HydroDIURIL Oral Product	1174811	RxNorm	YES	YES	NO
36237231	HydroDIURIL Pill	1174812	RxNorm	YES	YES	NO
36237459	Diuretic Ap-Es Oral Product	1173148	RxNorm	YES	YES	NO
36237460	Diuretic Ap-Es Pill	1173149	RxNorm	YES	YES	NO
36237783	Exforge HCT Oral Product	1173249	RxNorm	YES	YES	NO
36237784	Exforge HCT Pill	1173250	RxNorm	YES	YES	NO
36237852	Hydrap-ES Oral Product	1174064	RxNorm	YES	YES	NO
36237853	Hydrap-ES Pill	1174065	RxNorm	YES	YES	NO
36237869	Hydro-Reserp Oral Product	1174092	RxNorm	YES	YES	NO
36237870	Hydro-Reserp Pill	1174093	RxNorm	YES	YES	NO
36238273	azilsartan / chlorthalidone Oral Product	1235140	RxNorm	YES	YES	NO
36238274	azilsartan / chlorthalidone Pill	1235141	RxNorm	YES	YES	NO
36238510	Tribenzor Pill	1182147	RxNorm	YES	YES	NO
36238819	Monopril-HCT Pill	1182235	RxNorm	YES	YES	NO
36238820	Monopril-HCT Oral Product	1182236	RxNorm	YES	YES	NO
36239006	Zestoretic Oral Product	1187277	RxNorm	YES	YES	NO
36239007	Zestoretic Pill	1187278	RxNorm	YES	YES	NO
36239102	Tribenzor Oral Product	1182686	RxNorm	YES	YES	NO
36239296	Valturna Oral Product	1187346	RxNorm	YES	YES	NO
36239297	Valturna Pill	1187347	RxNorm	YES	YES	NO
36239382	Maxzide Oral Product	1182741	RxNorm	YES	YES	NO
36239383	Maxzide Pill	1182742	RxNorm	YES	YES	NO
36239638	Ziac Pill	1187449	RxNorm	YES	YES	NO
36239639	Ziac Oral Product	1187450	RxNorm	YES	YES	NO
36239650	Zida-Co Oral Product	1187471	RxNorm	YES	YES	NO
36239651	Zida-Co Pill	1187472	RxNorm	YES	YES	NO
36239801	Mepranix Oral Product	1184390	RxNorm	YES	YES	NO
36239802	Mepranix Pill	1184391	RxNorm	YES	YES	NO
36239983	Vaseretic Oral Product	1187581	RxNorm	YES	YES	NO
36239984	Vaseretic Pill	1187582	RxNorm	YES	YES	NO
36240204	Quinaretic Oral Product	1185902	RxNorm	YES	YES	NO
36240205	Quinaretic Pill	1185903	RxNorm	YES	YES	NO
36241084	Unipres Oral Product	1186281	RxNorm	YES	YES	NO
36241085	Unipres Pill	1186282	RxNorm	YES	YES	NO
36241087	Uniretic Oral Product	1186288	RxNorm	YES	YES	NO
36241088	Uniretic Pill	1186289	RxNorm	YES	YES	NO
36241277	Teveten HCT Oral Product	1184922	RxNorm	YES	YES	NO
36241278	Teveten HCT Pill	1184923	RxNorm	YES	YES	NO
36242838	Twynsta Pill	1186904	RxNorm	YES	YES	NO
36242839	Twynsta Oral Product	1186905	RxNorm	YES	YES	NO
36243159	Uni Serp Oral Product	1187843	RxNorm	YES	YES	NO
36243160	Uni Serp Pill	1187844	RxNorm	YES	YES	NO
36243282	Tenoret Pill	1182012	RxNorm	YES	YES	NO
36243283	Tenoretic Oral Product	1182013	RxNorm	YES	YES	NO
36243284	Tenoretic Pill	1182014	RxNorm	YES	YES	NO
36247927	Tekturna HCT Oral Product	1430140	RxNorm	YES	YES	NO
36247928	Tekturna HCT Pill	1430141	RxNorm	YES	YES	NO
36248677	sacubitril / valsartan Oral Product	1656336	RxNorm	YES	YES	NO
36248678	sacubitril / valsartan Pill	1656337	RxNorm	YES	YES	NO
36248703	amlodipine / perindopril Oral Product	1600713	RxNorm	YES	YES	NO
36248704	amlodipine / perindopril Pill	1600714	RxNorm	YES	YES	NO
36248705	Prestalia Oral Product	1600720	RxNorm	YES	YES	NO
36248706	Prestalia Pill	1600721	RxNorm	YES	YES	NO
36250179	nebivolol / valsartan Oral Product	1798277	RxNorm	YES	YES	NO
36250180	nebivolol / valsartan Pill	1798278	RxNorm	YES	YES	NO
36259265	Amlodipine / Indapamide / Perindopril Oral Tablet	OMOP3110140	RxNorm Extension	YES	YES	NO
36264366	Hydrochlorothiazide / Metoprolol Extended Release Oral Capsule	OMOP3115241	RxNorm Extension	YES	YES	NO
36264394	Bisoprolol / Hydrochlorothiazide Oral Capsule	OMOP3115269	RxNorm Extension	YES	YES	NO
36266935	Bisoprolol / Perindopril Oral Tablet	OMOP3117810	RxNorm Extension	YES	YES	NO
36269479	Hydrochlorothiazide / Losartan Oral Capsule	OMOP3120354	RxNorm Extension	YES	YES	NO
36272027	Hydrochlorothiazide / nebivolol Oral Tablet	OMOP3122902	RxNorm Extension	YES	YES	NO
36272030	Felodipine / Ramipril Extended Release Oral Capsule	OMOP3122905	RxNorm Extension	YES	YES	NO
36274581	Felodipine / Metoprolol Extended Release Oral Capsule	OMOP3125456	RxNorm Extension	YES	YES	NO
36274595	Chlorthalidone / Metoprolol Extended Release Oral Capsule	OMOP3125470	RxNorm Extension	YES	YES	NO
36784817	Bisoprolol / Hydrochlorothiazide Extended Release Oral Tablet	OMOP4773102	RxNorm Extension	YES	YES	NO
36786066	Cilazapril / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP4774342	RxNorm Extension	YES	YES	NO
36787123	Amlodipine / Hydrochlorothiazide / olmesartan Delayed Release Oral Tablet	OMOP4775385	RxNorm Extension	YES	YES	NO
36787465	eprosartan / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP4775731	RxNorm Extension	YES	YES	NO
36881813	Chlorthalidone / Metoprolol Delayed Release Oral Tablet	OMOP993857	RxNorm Extension	YES	YES	NO
36889540	Chlorthalidone / Oxprenolol Delayed Release Oral Tablet	OMOP1004099	RxNorm Extension	YES	YES	NO
40003426	acebutolol / nifedipine Oral Tablet	446671	RxNorm	YES	YES	NO
40007368	amiloride / atenolol / hydrochlorothiazide Oral Capsule	379257	RxNorm	YES	YES	NO
40007369	amiloride / atenolol / hydrochlorothiazide Oral Tablet	437781	RxNorm	YES	YES	NO
40007373	amiloride / furosemide / indapamide Oral Tablet	437571	RxNorm	YES	YES	NO
40007374	amiloride / furosemide Oral Tablet	370847	RxNorm	YES	YES	NO
40007377	amiloride / hydrochlorothiazide / methyldopa Oral Tablet	446454	RxNorm	YES	YES	NO
40007378	amiloride / hydrochlorothiazide / timolol Oral Tablet	379256	RxNorm	YES	YES	NO
40007379	amiloride / hydrochlorothiazide Oral Solution	370848	RxNorm	YES	YES	NO
40007380	amiloride / hydrochlorothiazide Oral Tablet	370638	RxNorm	YES	YES	NO
40010558	atenolol / bendroflumethiazide Oral Capsule	385565	RxNorm	YES	YES	NO
40010559	atenolol / chlorthalidone / hydralazine Oral Tablet	440424	RxNorm	YES	YES	NO
40010560	atenolol / chlorthalidone Oral Capsule	370958	RxNorm	YES	YES	NO
40010561	atenolol / chlorthalidone Oral Tablet	370620	RxNorm	YES	YES	NO
40010567	atenolol / nifedipine Extended Release Oral Capsule	393276	RxNorm	YES	YES	NO
40010568	atenolol / nifedipine Oral Capsule	370961	RxNorm	YES	YES	NO
40010569	atenolol / nifedipine Oral Tablet	376172	RxNorm	YES	YES	NO
40011854	bendroflumethiazide / propranolol Extended Release Oral Capsule	373656	RxNorm	YES	YES	NO
40011855	bendroflumethiazide / propranolol Oral Capsule	373655	RxNorm	YES	YES	NO
40011856	bendroflumethiazide / propranolol Oral Tablet	373657	RxNorm	YES	YES	NO
40011860	bendroflumethiazide / timolol Oral Tablet	374136	RxNorm	YES	YES	NO
40015092	bisoprolol / hydrochlorothiazide Oral Tablet	371103	RxNorm	YES	YES	NO
40020436	chlorothiazide / methyldopa Oral Tablet [Aldoclor]	368245	RxNorm	YES	YES	NO
40026132	clonidine / hydrochlorothiazide / triamterene Oral Tablet	438743	RxNorm	YES	YES	NO
40027598	cilazapril / hydrochlorothiazide Oral Tablet	371507	RxNorm	YES	YES	NO
40028109	cyclopenthiazide / oxprenolol Extended Release Oral Tablet	373186	RxNorm	YES	YES	NO
40028110	cyclopenthiazide / oxprenolol Oral Tablet	373185	RxNorm	YES	YES	NO
40030840	chlorthalidone / hydralazine / oxprenolol Oral Tablet	440427	RxNorm	YES	YES	NO
40030842	chlorthalidone / metoprolol Extended Release Oral Tablet	446468	RxNorm	YES	YES	NO
40030843	chlorthalidone / metoprolol Oral Tablet	379254	RxNorm	YES	YES	NO
40030844	chlorthalidone / oxprenolol Extended Release Oral Tablet	373182	RxNorm	YES	YES	NO
40030845	chlorthalidone / oxprenolol Oral Tablet	373181	RxNorm	YES	YES	NO
40033922	dihydralazine / propranolol Oral Tablet	439011	RxNorm	YES	YES	NO
40034892	diltiazem / hydrochlorothiazide Extended Release Oral Capsule	385943	RxNorm	YES	YES	NO
40037280	felodipine / metoprolol Extended Release Oral Tablet	439560	RxNorm	YES	YES	NO
40037281	felodipine / ramipril Oral Tablet	393440	RxNorm	YES	YES	NO
40039294	ergoloid mesylates, USP / nifedipine Oral Tablet	439288	RxNorm	YES	YES	NO
40039680	furosemide / spironolactone Oral Capsule	373944	RxNorm	YES	YES	NO
40039681	furosemide / spironolactone Oral Tablet	451932	RxNorm	YES	YES	NO
40039682	furosemide / triamterene Extended Release Oral Capsule	452294	RxNorm	YES	YES	NO
40039683	furosemide / triamterene Oral Tablet	374196	RxNorm	YES	YES	NO
40044449	hydralazine / hydrochlorothiazide / metoprolol Oral Tablet	440425	RxNorm	YES	YES	NO
40044821	hydrochlorothiazide / losartan Oral Tablet	372650	RxNorm	YES	YES	NO
40044824	hydrochlorothiazide / magnesium chloride / methotrimeprazine Oral Tablet	440593	RxNorm	YES	YES	NO
40044831	hydrochlorothiazide / metoprolol Extended Release Oral Tablet	372890	RxNorm	YES	YES	NO
40044832	hydrochlorothiazide / metoprolol Oral Tablet	372889	RxNorm	YES	YES	NO
40044834	hydrochlorothiazide / olmesartan Oral Tablet	406041	RxNorm	YES	YES	NO
40044837	hydrochlorothiazide / potassium chloride Oral Tablet	376241	RxNorm	YES	YES	NO
40044838	hydrochlorothiazide / propranolol Extended Release Oral Capsule	373650	RxNorm	YES	YES	NO
40044839	hydrochlorothiazide / propranolol Oral Tablet	373651	RxNorm	YES	YES	NO
40044851	hydrochlorothiazide / spironolactone Oral Tablet	370639	RxNorm	YES	YES	NO
40044854	hydrochlorothiazide / timolol Oral Tablet	374419	RxNorm	YES	YES	NO
40044856	hydrochlorothiazide / triamterene / verapamil Oral Tablet	452537	RxNorm	YES	YES	NO
40044857	hydrochlorothiazide / triamterene Oral Capsule	370640	RxNorm	YES	YES	NO
40045116	hydrochlorothiazide / triamterene Oral Tablet	374192	RxNorm	YES	YES	NO
40045118	hydrochlorothiazide / verapamil Extended Release Oral Capsule	452536	RxNorm	YES	YES	NO
40045119	hydrochlorothiazide / irbesartan Oral Tablet	370705	RxNorm	YES	YES	NO
40045121	hydrochlorothiazide / mepindolol Oral Tablet	446301	RxNorm	YES	YES	NO
40045124	hydrochlorothiazide / quinapril Oral Tablet	373732	RxNorm	YES	YES	NO
40045126	hydrochlorothiazide / telmisartan Oral Tablet	378921	RxNorm	YES	YES	NO
40045128	hydrochlorothiazide / valsartan Oral Tablet	374280	RxNorm	YES	YES	NO
40049453	indapamide / perindopril Oral Tablet	393357	RxNorm	YES	YES	NO
40054917	dehydrosanol / triamterene Oral Capsule	452289	RxNorm	YES	YES	NO
40054918	dehydrosanol / triamterene Oral Tablet	452285	RxNorm	YES	YES	NO
40059139	eprosartan / hydrochlorothiazide Oral Tablet	378735	RxNorm	YES	YES	NO
40060227	cyclothiazide / triamterene Oral Tablet	452292	RxNorm	YES	YES	NO
40061782	metoprolol / nifedipine Extended Release Oral Capsule	446677	RxNorm	YES	YES	NO
40065740	methyclothiazide / triamterene Oral Tablet	452299	RxNorm	YES	YES	NO
40085584	triamterene / xipamide Oral Tablet	452302	RxNorm	YES	YES	NO
40095410	candesartan / hydrochlorothiazide Oral Tablet	374934	RxNorm	YES	YES	NO
40096153	benazepril / hydrochlorothiazide Oral Tablet	371000	RxNorm	YES	YES	NO
40096806	benzthiazide / triamterene Oral Capsule	374195	RxNorm	YES	YES	NO
40099414	trandolapril / verapamil Extended Release Oral Capsule	379582	RxNorm	YES	YES	NO
40099416	trandolapril / verapamil Extended Release Oral Tablet	374178	RxNorm	YES	YES	NO
40137849	hydrochlorothiazide / methyldopa Oral Tablet [Aldoril]	688642	RxNorm	YES	YES	NO
40140541	amlodipine / valsartan Oral Tablet	722125	RxNorm	YES	YES	NO
40142669	amlodipine / olmesartan Oral Tablet	730860	RxNorm	YES	YES	NO
40147525	aliskiren / hydrochlorothiazide Oral Tablet	754717	RxNorm	YES	YES	NO
40160338	amlodipine / hydrochlorothiazide / valsartan Oral Tablet	848130	RxNorm	YES	YES	NO
40167838	amlodipine / telmisartan Oral Tablet	876513	RxNorm	YES	YES	NO
40224153	amlodipine / hydrochlorothiazide / olmesartan Oral Tablet	999966	RxNorm	YES	YES	NO
40232328	aliskiren / amlodipine / hydrochlorothiazide Oral Tablet	1050796	RxNorm	YES	YES	NO
40749849	Chlorothiazide / Spironolactone Oral Powder	OMOP4707410	RxNorm Extension	YES	YES	NO
40830512	Hydrochlorothiazide / Reserpine / Triamterene Oral Tablet	OMOP2028474	RxNorm Extension	YES	YES	NO
40830513	european olive pollen extract / Hydrochlorothiazide / Potassium Oral Tablet	OMOP2028475	RxNorm Extension	YES	YES	NO
40893011	Dihydralazine / Hydrochlorothiazide / Potassium / Reserpine Oral Tablet	OMOP2090973	RxNorm Extension	YES	YES	NO
40924218	Canrenoic Acid / Furosemide / Phosphoric acid Injectable Solution	OMOP2122180	RxNorm Extension	YES	YES	NO
40924457	Amiloride / Timolol Oral Tablet	OMOP2122419	RxNorm Extension	YES	YES	NO
40955187	Hydrochlorothiazide / Potassium / Rauwolfia preparation / rescinnamine / Reserpine / Vitamin A / Vitamin E Oral Tablet	OMOP2153149	RxNorm Extension	YES	YES	NO
40955683	Alprenolol / Hydrochlorothiazide Oral Tablet	OMOP2153645	RxNorm Extension	YES	YES	NO
40986248	Propranolol / Valeriana officinalis whole extract Oral Capsule	OMOP2184210	RxNorm Extension	YES	YES	NO
40986369	Hydrochlorothiazide / Propranolol / Triamterene Oral Capsule	OMOP2184331	RxNorm Extension	YES	YES	NO
40986688	Bunitrolol / Hydrochlorothiazide / Triamterene Extended Release Oral Capsule	OMOP2184650	RxNorm Extension	YES	YES	NO
41017227	trandolapril / Verapamil Oral Tablet	OMOP2215189	RxNorm Extension	YES	YES	NO
41048702	Hydrochlorothiazide / Oxprenolol Oral Tablet	OMOP2246664	RxNorm Extension	YES	YES	NO
41080575	Amlodipine / Losartan Oral Tablet	OMOP2278537	RxNorm Extension	YES	YES	NO
41111670	Canrenoic Acid / Furosemide Injectable Solution	OMOP2309632	RxNorm Extension	YES	YES	NO
41143011	Felodipine / Metoprolol Oral Tablet	OMOP2340973	RxNorm Extension	YES	YES	NO
41143341	dehydrosanol / Hesperidin / Thiamine / Triamterene Oral Tablet	OMOP2341303	RxNorm Extension	YES	YES	NO
41174430	Amlodipine / Bisoprolol Oral Tablet	OMOP2372392	RxNorm Extension	YES	YES	NO
41174481	Aesculus hippocastanum bark extract / Hydrochlorothiazide / Triamterene Oral Tablet	OMOP2372443	RxNorm Extension	YES	YES	NO
41205367	Propranolol / Spironolactone Oral Tablet	OMOP2403329	RxNorm Extension	YES	YES	NO
41205620	Dihydroergotoxine / Nifedipine Oral Tablet	OMOP2403582	RxNorm Extension	YES	YES	NO
41236870	Amlodipine / candesartan Oral Capsule	OMOP2434832	RxNorm Extension	YES	YES	NO
41237790	Mefruside / Methyldopa Oral Tablet [Sali Presinol]	OMOP2435752	RxNorm Extension	YES	YES	NO
41238954	buthiazide / Methyldopa Oral Tablet [Sembrina]	OMOP2436916	RxNorm Extension	YES	YES	NO
41267737	Bupranolol / dehydrosanol / Triamterene Oral Tablet	OMOP2465699	RxNorm Extension	YES	YES	NO
41298388	Furosemide / Reserpine Oral Tablet	OMOP2496350	RxNorm Extension	YES	YES	NO
41298962	6-(Diethylaminomethyl)Rutin / CRATAEGUS LAEVIGATA FRUIT / Hexamethonium Hydroxide / Hydrochlorothiazide / Potassium / Rauwolfia preparation / Reserpine Oral Tablet	OMOP2496924	RxNorm Extension	YES	YES	NO
41299800	Mefruside / Methyldopa / Reserpine Oral Tablet [Caprinol]	OMOP2497762	RxNorm Extension	YES	YES	NO
42479214	Felodipine / Ramipril Extended Release Oral Tablet	OMOP419678	RxNorm Extension	YES	YES	NO
42705336	azilsartan / chlorthalidone Oral Tablet	1235142	RxNorm	YES	YES	NO
42874880	Felodipine / Ramipril Delayed Release Oral Tablet	OMOP4871998	RxNorm Extension	YES	YES	NO
42875928	Amlodipine / Hydrochlorothiazide / Ramipril Oral Capsule	OMOP4873041	RxNorm Extension	YES	YES	NO
42938519	Amlodipine / Hydrochlorothiazide / telmisartan Oral Tablet	OMOP4665192	RxNorm Extension	YES	YES	NO
42948657	lercanidipine / valsartan Oral Tablet	OMOP4675247	RxNorm Extension	YES	YES	NO
42950872	Amlodipine / Chlorthalidone / Losartan Oral Tablet	OMOP4677445	RxNorm Extension	YES	YES	NO
42960011	Amlodipine / fimasartan potassium Oral Tablet	OMOP4686518	RxNorm Extension	YES	YES	NO
42960024	fimasartan potassium / Hydrochlorothiazide Oral Tablet	OMOP4686530	RxNorm Extension	YES	YES	NO
42972643	atorvastatin / irbesartan Oral Tablet	OMOP4699050	RxNorm Extension	YES	YES	NO
43022805	carvedilol / ivabradine Delayed Release Oral Tablet	OMOP4837934	RxNorm Extension	YES	YES	NO
43134832	Hydrochlorothiazide / Losartan Delayed Release Oral Tablet	OMOP447236	RxNorm Extension	YES	YES	NO
43156974	aliskiren / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP447297	RxNorm Extension	YES	YES	NO
43157075	Hydrochlorothiazide / quinapril Delayed Release Oral Tablet	OMOP448040	RxNorm Extension	YES	YES	NO
43166576	benazepril / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP485878	RxNorm Extension	YES	YES	NO
43167787	Hydrochlorothiazide / olmesartan Delayed Release Oral Tablet	OMOP446318	RxNorm Extension	YES	YES	NO
43178952	Hydrochlorothiazide / zofenopril Delayed Release Oral Tablet	OMOP447280	RxNorm Extension	YES	YES	NO
43188587	Atenolol / Chlorthalidone Delayed Release Oral Tablet	OMOP488010	RxNorm Extension	YES	YES	NO
43189757	Hydrochlorothiazide / irbesartan Delayed Release Oral Tablet	OMOP446394	RxNorm Extension	YES	YES	NO
43189944	Hydrochlorothiazide / nebivolol Delayed Release Oral Tablet	OMOP448113	RxNorm Extension	YES	YES	NO
43193525	Indapamide / Perindopril Delayed Release Oral Tablet	OMOP480217	RxNorm Extension	YES	YES	NO
43199873	Hydrochlorothiazide / valsartan Delayed Release Oral Tablet	OMOP510396	RxNorm Extension	YES	YES	NO
43199916	Amlodipine / Hydrochlorothiazide / valsartan Delayed Release Oral Tablet	OMOP514110	RxNorm Extension	YES	YES	NO
43203499	Amlodipine / Indapamide Extended Release Oral Tablet	OMOP470511	RxNorm Extension	YES	YES	NO
43205563	Enalapril / lercanidipine Delayed Release Oral Tablet	OMOP489591	RxNorm Extension	YES	YES	NO
43211738	Bisoprolol / Hydrochlorothiazide Delayed Release Oral Tablet	OMOP447790	RxNorm Extension	YES	YES	NO
43260913	Enalapril / lercanidipine Oral Tablet	OMOP530577	RxNorm Extension	YES	YES	NO
43585468	ivabradine / Metoprolol Oral Tablet	OMOP954444	RxNorm Extension	YES	YES	NO
43599922	dehydrosanol / Triamterene Delayed Release Oral Tablet	OMOP778743	RxNorm Extension	YES	YES	NO
43636119	Hydrochlorothiazide / zofenopril Oral Tablet	OMOP789674	RxNorm Extension	YES	YES	NO
43672256	Hydrochlorothiazide / Propranolol / Triamterene Oral Tablet	OMOP781184	RxNorm Extension	YES	YES	NO
43677126	Amlodipine / Ramipril Oral Capsule	OMOP670769	RxNorm Extension	YES	YES	NO
43725912	Bendroflumethiazide / Hydralazine / Propranolol Oral Capsule	OMOP778561	RxNorm Extension	YES	YES	NO
43748731	Enalapril / Nitrendipine Oral Tablet	OMOP671132	RxNorm Extension	YES	YES	NO
43749671	Amlodipine / candesartan Oral Tablet	OMOP687193	RxNorm Extension	YES	YES	NO
43839612	Amlodipine / Lisinopril Oral Tablet	OMOP682928	RxNorm Extension	YES	YES	NO
44031088	Hydrochlorothiazide / Methyldopa Oral Tablet [Aldoril 25]	OMOP1025719	RxNorm Extension	YES	YES	NO
44031476	Chlorothiazide / Methyldopa Oral Tablet [Supres]	OMOP1026107	RxNorm Extension	YES	YES	NO
44057083	Hydrochlorothiazide / Methyldopa Oral Tablet [Pms-Dopazide]	OMOP1051714	RxNorm Extension	YES	YES	NO
44069972	Hydrochlorothiazide / Methyldopa Oral Tablet [Aldoril 15]	OMOP1064603	RxNorm Extension	YES	YES	NO
44082841	Hydrochlorothiazide / Methyldopa Oral Tablet [Novo-Doparil]	OMOP1077472	RxNorm Extension	YES	YES	NO
44095788	Hydrochlorothiazide / Methyldopa Oral Tablet [Apo Methazide]	OMOP1090419	RxNorm Extension	YES	YES	NO
45892980	amlodipine / perindopril Oral Tablet	1600715	RxNorm	YES	YES	NO

A.4.7 Concept: Hypertension

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
320128	Essential hypertension	59621000	SNOMED	NO	YES	NO
4034031	Benign essential hypertension complicating AND/OR reason for care during pregnancy	23717007	SNOMED	YES	YES	NO
4083723	Essential hypertension complicating AND/OR reason for care during childbirth	18416000	SNOMED	YES	YES	NO
4215640	Benign essential hypertension complicating AND/OR reason for care during childbirth	71874008	SNOMED	YES	YES	NO
4302591	Essential hypertension complicating AND/OR reason for care during pregnancy	78808002	SNOMED	YES	YES	NO

A.4.8 Concept: Antihypertensives

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
904542	triamterene	10763	RxNorm	NO	YES	NO
907013	metolazone	6916	RxNorm	NO	YES	NO
932745	bumetanide	1808	RxNorm	NO	YES	NO
942350	torsemide	38413	RxNorm	NO	YES	NO
956874	furosemide	4603	RxNorm	NO	YES	NO
970250	spironolactone	9997	RxNorm	NO	YES	NO
974166	hydrochlorothiazide	5487	RxNorm	NO	YES	NO
978555	indapamide	5764	RxNorm	NO	YES	NO
991382	amiloride	644	RxNorm	NO	YES	NO
1305447	methyldopa	6876	RxNorm	NO	YES	NO
1307046	metoprolol	6918	RxNorm	NO	YES	NO
1307863	verapamil	11170	RxNorm	NO	YES	NO
1308216	lisinopril	29046	RxNorm	NO	YES	NO
1308842	valsartan	69749	RxNorm	NO	YES	NO
1309068	minoxidil	6984	RxNorm	NO	YES	NO
1309799	eplerenone	298869	RxNorm	NO	YES	NO
1310756	moexipril	30131	RxNorm	NO	YES	NO
1313200	nadolol	7226	RxNorm	NO	YES	NO
1314002	atenolol	1202	RxNorm	NO	YES	NO
1314577	nebivolol	31555	RxNorm	NO	YES	NO
1317640	telmisartan	73494	RxNorm	NO	YES	NO
1317967	aliskiren	325646	RxNorm	NO	YES	NO
1318137	nicardipine	7396	RxNorm	NO	YES	NO
1318853	nifedipine	7417	RxNorm	NO	YES	NO
1319880	nisoldipine	7435	RxNorm	NO	YES	NO
1319998	acebutolol	149	RxNorm	NO	YES	NO
1322081	betaxolol	1520	RxNorm	NO	YES	NO
1326012	isradipine	33910	RxNorm	NO	YES	NO
1327978	penbutolol	7973	RxNorm	NO	YES	NO
1328165	diltiazem	3443	RxNorm	NO	YES	NO
1331235	quinapril	35208	RxNorm	NO	YES	NO
1332418	amlodipine	17767	RxNorm	NO	YES	NO
1334456	ramipril	35296	RxNorm	NO	YES	NO
1335471	benazepril	18867	RxNorm	NO	YES	NO
1338005	bisoprolol	19484	RxNorm	NO	YES	NO
1340128	captopril	1998	RxNorm	NO	YES	NO
1341238	terazosin	37798	RxNorm	NO	YES	NO
1341927	enalapril	3827	RxNorm	NO	YES	NO
1342439	trandolapril	38454	RxNorm	NO	YES	NO
1344965	guanfacine	40114	RxNorm	NO	YES	NO
1345858	pindolol	8332	RxNorm	NO	YES	NO
1346686	eprosartan	83515	RxNorm	NO	YES	NO
1346823	carvedilol	20352	RxNorm	NO	YES	NO
1347384	irbesartan	83818	RxNorm	NO	YES	NO
1350489	prazosin	8629	RxNorm	NO	YES	NO
1351557	candesartan	214354	RxNorm	NO	YES	NO
1353766	propranolol	8787	RxNorm	NO	YES	NO
1353776	felodipine	4316	RxNorm	NO	YES	NO
1363053	doxazosin	49276	RxNorm	NO	YES	NO
1363749	fosinopril	50166	RxNorm	NO	YES	NO
1367500	losartan	52175	RxNorm	NO	YES	NO
1373225	perindopril	54552	RxNorm	NO	YES	NO
1373928	hydralazine	5470	RxNorm	NO	YES	NO
1386957	labetalol	6185	RxNorm	NO	YES	NO
1395058	chlorthalidone	2409	RxNorm	NO	YES	NO
1398937	clonidine	2599	RxNorm	NO	YES	NO
40226742	olmesartan	321064	RxNorm	NO	YES	NO
40235485	azilsartan	1091643	RxNorm	NO	YES	NO

A.4.9 Concept: Other agents

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
904542	triamterene	10763	RxNorm	NO	YES	NO
907013	metolazone	6916	RxNorm	NO	YES	NO
932745	bumetanide	1808	RxNorm	NO	YES	NO
942350	torsemide	38413	RxNorm	NO	YES	NO
956874	furosemide	4603	RxNorm	NO	YES	NO
970250	spironolactone	9997	RxNorm	NO	YES	NO
974166	hydrochlorothiazide	5487	RxNorm	NO	YES	NO
978555	indapamide	5764	RxNorm	NO	YES	NO
991382	amiloride	644	RxNorm	NO	YES	NO
1305447	methyldopa	6876	RxNorm	NO	YES	NO
1307046	metoprolol	6918	RxNorm	NO	YES	NO
1307863	verapamil	11170	RxNorm	NO	YES	NO
1308216	lisinopril	29046	RxNorm	NO	YES	NO
1308842	valsartan	69749	RxNorm	NO	YES	NO
1309068	minoxidil	6984	RxNorm	NO	YES	NO
1309799	eplerenone	298869	RxNorm	NO	YES	NO
1310756	moexipril	30131	RxNorm	NO	YES	NO
1313200	nadolol	7226	RxNorm	NO	YES	NO
1314002	atenolol	1202	RxNorm	NO	YES	NO
1314577	nebivolol	31555	RxNorm	NO	YES	NO
1317640	telmisartan	73494	RxNorm	NO	YES	NO
1317967	aliskiren	325646	RxNorm	NO	YES	NO
1318137	nicardipine	7396	RxNorm	NO	YES	NO
1318853	nifedipine	7417	RxNorm	NO	YES	NO
1319880	nisoldipine	7435	RxNorm	NO	YES	NO
1322081	betaxolol	1520	RxNorm	NO	YES	NO
1326012	isradipine	33910	RxNorm	NO	YES	NO
1327978	penbutolol	7973	RxNorm	NO	YES	NO
1328165	diltiazem	3443	RxNorm	NO	YES	NO
1331235	quinapril	35208	RxNorm	NO	YES	NO
1334456	ramipril	35296	RxNorm	NO	YES	NO
1335471	benazepril	18867	RxNorm	NO	YES	NO
1338005	bisoprolol	19484	RxNorm	NO	YES	NO
1340128	captopril	1998	RxNorm	NO	YES	NO
1341238	terazosin	37798	RxNorm	NO	YES	NO
1341927	enalapril	3827	RxNorm	NO	YES	NO
1342439	trandolapril	38454	RxNorm	NO	YES	NO
1344965	guanfacine	40114	RxNorm	NO	YES	NO
1345858	pindolol	8332	RxNorm	NO	YES	NO
1346686	eprosartan	83515	RxNorm	NO	YES	NO
1346823	carvedilol	20352	RxNorm	NO	YES	NO
1347384	irbesartan	83818	RxNorm	NO	YES	NO
1350489	prazosin	8629	RxNorm	NO	YES	NO
1351557	candesartan	214354	RxNorm	NO	YES	NO
1353766	propranolol	8787	RxNorm	NO	YES	NO
1353776	felodipine	4316	RxNorm	NO	YES	NO
1363053	doxazosin	49276	RxNorm	NO	YES	NO
1363749	fosinopril	50166	RxNorm	NO	YES	NO
1367500	losartan	52175	RxNorm	NO	YES	NO
1373225	perindopril	54552	RxNorm	NO	YES	NO
1373928	hydralazine	5470	RxNorm	NO	YES	NO
1386957	labetalol	6185	RxNorm	NO	YES	NO
1395058	chlorthalidone	2409	RxNorm	NO	YES	NO
1398937	clonidine	2599	RxNorm	NO	YES	NO
40226742	olmesartan	321064	RxNorm	NO	YES	NO
40235485	azilsartan	1091643	RxNorm	NO	YES	NO
1332418	amlodipine	17767	RxNorm	YES	YES	NO
1319998	acebutolol	149	RxNorm	YES	YES	NO

A.4.10 Concept: Previous CV events including acute MI, stroke, HF

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
372924	Cerebral artery occlusion	20059004	SNOMED	NO	NO	NO
375557	Cerebral embolism	75543006	SNOMED	NO	NO	NO
376713	Cerebral hemorrhage	274100004	SNOMED	NO	NO	NO
432923	Subarachnoid hemorrhage	21454007	SNOMED	NO	NO	NO
439847	Intracranial hemorrhage	1386000	SNOMED	NO	NO	NO
441874	Cerebral thrombosis	71444005	SNOMED	NO	NO	NO
316139	Heart failure	84114007	SNOMED	NO	YES	NO
443454	Cerebral infarction	432504007	SNOMED	NO	YES	NO
4329847	Myocardial infarction	22298006	SNOMED	NO	YES	NO
314666	Old myocardial infarction	1755008	SNOMED	YES	YES	NO
315295	Congestive rheumatic heart failure	82523003	SNOMED	YES	YES	NO

B Outcome Cohort Definitions

B.1 3-point MACE

B.1.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘Acute myocardial Infarction’.
condition occurrences of ‘Sudden cardiac death’.
condition occurrences of ‘Ischemic stroke’.
condition occurrences of ’ Intracranial bleed Hemorrhagic stroke’.

Restrict entry events to having at least 1 visit occurrence of ‘Inpatient or ER visit’, starting anytime on or before cohort entry start date and ending between 0 days before and all days after cohort entry start date.

B.1.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.1.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.1.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.1.5 Concept: Acute myocardial Infarction

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4329847	Myocardial infarction	22298006	SNOMED	NO	YES	NO
314666	Old myocardial infarction	1755008	SNOMED	YES	YES	NO

B.1.6 Concept: Sudden cardiac death

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4048809	Brainstem death	230802007	SNOMED	NO	YES	NO
321042	Cardiac arrest	410429000	SNOMED	NO	YES	NO
442289	Death in less than 24 hours from onset of symptoms	53559009	SNOMED	NO	YES	NO
4317150	Sudden cardiac death	95281009	SNOMED	NO	YES	NO
4132309	Sudden death	26636000	SNOMED	NO	YES	NO
437894	Ventricular fibrillation	71908006	SNOMED	YES	YES	NO

B.1.7 Concept: Ischemic stroke

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
372924	Cerebral artery occlusion	20059004	SNOMED	NO	NO	NO
375557	Cerebral embolism	75543006	SNOMED	NO	NO	NO
443454	Cerebral infarction	432504007	SNOMED	NO	YES	NO
441874	Cerebral thrombosis	71444005	SNOMED	NO	NO	NO

B.1.8 Concept: Intracranial bleed Hemorrhagic stroke

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
376713	Cerebral hemorrhage	274100004	SNOMED	NO	NO	NO
439847	Intracranial hemorrhage	1386000	SNOMED	NO	NO	NO
432923	Subarachnoid hemorrhage	21454007	SNOMED	NO	NO	NO
43530727	Spontaneous cerebral hemorrhage	291571000119106	SNOMED	NO	NO	NO
4148906	Spontaneous subarachnoid hemorrhage	270907008	SNOMED	NO	NO	NO

B.1.9 Concept: Heart Failure

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
315295	Congestive rheumatic heart failure	82523003	SNOMED	YES	YES	NO
316139	Heart failure	84114007	SNOMED	NO	YES	NO

B.2 4-point MACE

B.2.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘Acute myocardial Infarction’.
condition occurrences of ‘Sudden cardiac death’.
condition occurrences of ‘Ischemic stroke’.
condition occurrences of ‘Iintracranial bleed Hemorrhagic stroke’.
condition occurrences of ‘Heart Failure’.

B.2.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.2.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.2.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.2.5 Concept: Acute myocardial Infarction

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4329847	Myocardial infarction	22298006	SNOMED	NO	YES	NO
314666	Old myocardial infarction	1755008	SNOMED	YES	YES	NO

B.2.6 Concept: Sudden cardiac death

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4048809	Brainstem death	230802007	SNOMED	NO	YES	NO
321042	Cardiac arrest	410429000	SNOMED	NO	YES	NO
442289	Death in less than 24 hours from onset of symptoms	53559009	SNOMED	NO	YES	NO
4317150	Sudden cardiac death	95281009	SNOMED	NO	YES	NO
4132309	Sudden death	26636000	SNOMED	NO	YES	NO
437894	Ventricular fibrillation	71908006	SNOMED	YES	YES	NO

B.2.7 Concept: Ischemic stroke

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
372924	Cerebral artery occlusion	20059004	SNOMED	NO	NO	NO
375557	Cerebral embolism	75543006	SNOMED	NO	NO	NO
443454	Cerebral infarction	432504007	SNOMED	NO	YES	NO
441874	Cerebral thrombosis	71444005	SNOMED	NO	NO	NO

B.2.8 Concept: Iintracranial bleed Hemorrhagic stroke

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
376713	Cerebral hemorrhage	274100004	SNOMED	NO	NO	NO
439847	Intracranial hemorrhage	1386000	SNOMED	NO	NO	NO
432923	Subarachnoid hemorrhage	21454007	SNOMED	NO	NO	NO
43530727	Spontaneous cerebral hemorrhage	291571000119106	SNOMED	NO	NO	NO
4148906	Spontaneous subarachnoid hemorrhage	270907008	SNOMED	NO	NO	NO

B.2.9 Concept: Heart Failure

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
315295	Congestive rheumatic heart failure	82523003	SNOMED	YES	YES	NO
316139	Heart failure	84114007	SNOMED	NO	YES	NO

B.3 Abdominal pain

B.3.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Abdominal pain’.

B.3.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.3.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.3.4 Concept: [LEGEND HTN] Abdominal pain

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
200219	Abdominal pain	21522001	SNOMED	NO	YES	NO

B.4 Abnormal weight gain

B.4.1 Cohort Entry Events

People enter the cohort when observing any of the following:

observations of ‘[LEGEND HTN] Abnormal weight gain’.

B.4.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.4.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.4.4 Concept: [LEGEND HTN] Abnormal weight gain

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
439141	Abnormal weight gain	161833006	SNOMED	NO	YES	NO

B.5 Abnormal weight loss

B.5.1 Cohort Entry Events

People enter the cohort when observing any of the following:

observations of ‘[LEGEND HTN] Abnormal weight loss’.

B.5.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.5.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.5.4 Concept: [LEGEND HTN] Abnormal weight loss

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
435928	Abnormal weight loss	267024001	SNOMED	NO	YES	NO
40303297	Weight loss (& abnormal)	139091004	SNOMED	NO	NO	NO

B.6 Acute myocardial infarction

B.6.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND-HtnStepCare] Acute myocardial Infarction’.

B.6.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.6.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.6.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.6.5 Concept: [LEGEND-HtnStepCare] Acute myocardial Infarction

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4329847	Myocardial infarction	22298006	SNOMED	NO	YES	NO
314666	Old myocardial infarction	1755008	SNOMED	YES	YES	NO

B.7 Acute pancreatitis

B.7.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Acute pancreatitis’.

B.7.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.7.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.7.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.7.5 Concept: [LEGEND HTN] Acute pancreatitis

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
199074	Acute pancreatitis	197456007	SNOMED	NO	YES	NO
2109394	Placement of drains, peripancreatic, for acute pancreatitis	48000	CPT4	NO	NO	NO
2109400	Resection or debridement of pancreas and peripancreatic tissue for acute necrotizing pancreatitis	48105	CPT4	NO	NO	NO
2109395	Placement of drains, peripancreatic, for acute pancreatitis; with cholecystostomy, gastrostomy, and jejunostomy	48001	CPT4	NO	NO	NO
42737025	Resection or debridement of pancreas and peripancreatic tissue for acute necrotizing pancreatitis (Deprecated)	48005	CPT4	NO	NO	NO

B.8 Acute renal failure

B.8.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘Acute Renal Failure’.

B.8.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 30 days.

B.8.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.8.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.8.5 Concept: Acute Renal Failure

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
197320	Acute renal failure syndrome	14669001	SNOMED	NO	YES	NO
432961	Acute renal papillary necrosis with renal failure	298015003	SNOMED	NO	YES	NO
444044	Acute tubular necrosis	35455006	SNOMED	NO	YES	NO

B.9 All-cause mortality

B.9.1 Cohort Entry Events

People enter the cohort when observing any of the following:

death of any form.

Limit cohort entry events to the earliest event per person.

B.9.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.9.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.10 Anaphylactoid reaction

B.10.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Anaphylactoid reaction’.

B.10.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.10.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 7 days of each other.

B.10.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.10.5 Concept: [LEGEND HTN] Angioedema

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
432791	Angioedema	41291007	SNOMED	NO	YES	NO

B.10.6 Concept: [LEGEND HTN] Anaphylactoid reaction

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
441202	Anaphylaxis	39579001	SNOMED	NO	YES	NO
4330225	Anaphylaxis due to hymenoptera venom	430980000	SNOMED	YES	YES	NO
40479646	Anaphylaxis due to latex	441593005	SNOMED	YES	YES	NO
4299299	Anaphylaxis secondary to bite and/or sting	402391007	SNOMED	YES	YES	NO
4084633	Bee sting-induced anaphylaxis	241931004	SNOMED	YES	YES	NO
434219	Food anaphylaxis	91941002	SNOMED	YES	YES	NO
4086737	Insulin-induced anaphylaxis	241939002	SNOMED	YES	YES	NO
4084634	Wasp sting-induced anaphylaxis	241932006	SNOMED	YES	YES	NO

B.11 Anemia

B.11.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Anemia’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.11.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.11.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.11.4 Concept: [LEGEND HTN] Anemia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
439777	Anemia	271737000	SNOMED	NO	YES	NO
137829	Aplastic anemia	306058006	SNOMED	NO	YES	NO
437090	Hemolytic disease of fetus OR newborn due to ABO immunization	32858009	SNOMED	YES	YES	NO
440218	Hemolytic disease of fetus OR newborn due to isoimmunization	387705004	SNOMED	YES	YES	NO
25518	Sickle cell trait	16402000	SNOMED	NO	YES	NO
24006	Sickle cell-hemoglobin C disease	35434009	SNOMED	NO	YES	NO
4301602	Thrombotic thrombocytopenic purpura	78129009	SNOMED	YES	YES	NO

B.12 Angioedema

B.12.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Angioedema’.

B.12.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.12.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.12.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.12.5 Concept: [LEGEND HTN] Angioedema

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
432791	Angioedema	41291007	SNOMED	NO	YES	NO

B.13 Anxiety

B.13.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Anxiety’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to with any of the following criteria:

having at least 1 condition occurrence of ‘[LEGEND HTN] Anxiety’, starting 1 days after cohort entry start date.
having at least 1 drug exposure of ‘[LEGEND HTN] Drugs to treat anxiety’, starting between 0 days before and 30 days after cohort entry start date.

B.13.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.13.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.13.4 Concept: [LEGEND HTN] Anxiety

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
442077	Anxiety disorder	197480006	SNOMED	NO	NO	NO
37109206	Anxiety disorder caused by drug	22621000119103	SNOMED	NO	YES	NO
4199892	Anxiety disorder due to a general medical condition	52910006	SNOMED	NO	YES	NO
434613	Generalized anxiety disorder	21897009	SNOMED	NO	YES	NO
4338031	Mixed anxiety and depressive disorder	231504006	SNOMED	NO	YES	NO
381537	Organic anxiety disorder	17496003	SNOMED	NO	YES	NO
436074	Panic disorder	371631005	SNOMED	NO	YES	NO
4304010	Phobic disorder	386810004	SNOMED	YES	YES	NO

B.13.5 Concept: [LEGEND HTN] Drugs to treat depression

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
21604686	ANTIDEPRESSANTS	N06A	ATC	NO	YES	NO

B.13.6 Concept: [LEGEND HTN] Drugs to treat anxiety

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
781039	Alprazolam	596	RxNorm	NO	YES	NO
733301	Buspirone	1827	RxNorm	NO	YES	NO
990678	Chlordiazepoxide	2356	RxNorm	NO	YES	NO
797617	Citalopram	2556	RxNorm	NO	YES	NO
19050832	clobazam	21241	RxNorm	NO	YES	NO
798874	Clonazepam	2598	RxNorm	NO	YES	NO
790253	clorazepate	2353	RxNorm	NO	YES	NO
717607	Desvenlafaxine	734064	RxNorm	NO	YES	NO
723013	Diazepam	3322	RxNorm	NO	YES	NO
739323	Droperidol	3648	RxNorm	NO	YES	NO
715259	duloxetine	72625	RxNorm	NO	YES	NO
715939	Escitalopram	321988	RxNorm	NO	YES	NO
755695	Fluoxetine	4493	RxNorm	NO	YES	NO
751412	Fluvoxamine	42355	RxNorm	NO	YES	NO
777221	Hydroxyzine	5553	RxNorm	NO	YES	NO
791967	Lorazepam	6470	RxNorm	NO	YES	NO
702865	Meprobamate	6760	RxNorm	NO	YES	NO
724816	Oxazepam	7781	RxNorm	NO	YES	NO
722031	Paroxetine	32937	RxNorm	NO	YES	NO
739138	Sertraline	36437	RxNorm	NO	YES	NO
743670	venlafaxine	39786	RxNorm	NO	YES	NO

B.13.7 Concept: [LEGEND HTN] Depression

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
442306	Adjustment disorder with depressed mood	57194009	SNOMED	NO	YES	NO
436665	Bipolar disorder	13746004	SNOMED	YES	YES	NO
440383	Depressive disorder	35489007	SNOMED	NO	YES	NO
4175329	Organic mood disorder of depressed type	42594001	SNOMED	NO	YES	NO

B.14 Bone fracture

B.14.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘Bone fracture’.

B.14.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.14.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.14.4 Concept: Bone fracture

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
75053	Fracture of bone	125605004	SNOMED	NO	YES	NO
4071354	Open reduction of fracture with internal fixation	20701002	SNOMED	NO	YES	NO

B.15 Bradycardia

B.15.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Bradycardia’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to having at least 1 condition occurrence of ‘[LEGEND HTN] Bradycardia’, starting 1 days after cohort entry start date.

B.15.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.15.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.15.4 Concept: [LEGEND HTN] Bradycardia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4169095	Bradycardia	48867003	SNOMED	NO	YES	NO
316999	Conduction disorder of the heart	44808001	SNOMED	NO	NO	NO
4171683	Sinus bradycardia	49710005	SNOMED	NO	YES	NO
317302	Sinus node dysfunction	60423000	SNOMED	NO	YES	NO

B.16 Cardiac arrhythmia

B.16.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Cardiac arrhythmia’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to with any of the following criteria:

having at least 1 condition occurrence of ‘[LEGEND HTN] Cardiac arrhythmia’, starting 1 days after cohort entry start date.
having at least 2 drug exposures of ‘[LEGEND HTN] Drugs used to treat cardiac arrhythmia’, starting between 0 days before and all days after cohort entry start date.
having at least 1 procedure occurrence of ‘[LEGEND HTN] Procedures to treat cardiac arrhythmia’, starting between 0 days before and all days after cohort entry start date.

B.16.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.16.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.16.4 Concept: [LEGEND HTN] Cardiac arrhythmia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
44784217	Cardiac arrhythmia	698247007	SNOMED	NO	YES	NO
38001137	Cardiac arrhythmia & conduction disorders w CC	309	DRG	NO	YES	NO
38001138	Cardiac arrhythmia & conduction disorders w/o CC/MCC	310	DRG	NO	YES	NO
315078	Palpitations	80313002	SNOMED	NO	YES	NO
444070	Tachycardia	3424008	SNOMED	NO	YES	NO

B.16.5 Concept: [LEGEND HTN] Drugs used to treat cardiac arrhythmia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
21600248	ANTIARRHYTHMICS, CLASS I AND III	C01B	ATC	NO	YES	NO
43013024	apixaban	1364430	RxNorm	NO	YES	NO
40228152	dabigatran etexilate	1037042	RxNorm	NO	YES	NO
40241331	rivaroxaban	1114195	RxNorm	NO	YES	NO
1310149	Warfarin	11289	RxNorm	NO	YES	NO
1309204	Adenosine	296	RxNorm	NO	YES	NO
45892847	edoxaban	1599538	RxNorm	NO	YES	NO

B.16.6 Concept: [LEGEND HTN] Procedures to treat cardiac arrhythmia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
45890325	Cardioversion, elective, electrical conversion of arrhythmia	1012978	CPT4	NO	YES	NO
45890400	Operative tissue ablation and reconstruction of atria, extensive (eg, maze procedure)	1014679	CPT4	NO	YES	NO
2107068	Operative tissue ablation and reconstruction of atria, performed at the time of other cardiac procedure(s), extensive (eg, maze procedure), with cardiopulmonary bypass (List separately in addition to code for primary procedure)	33259	CPT4	NO	YES	NO
4051932	Procedure for arrhythmia	233154000	SNOMED	NO	YES	NO

B.17 Chest pain

B.17.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Chest pain or angina’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.17.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.17.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.17.4 Concept: [LEGEND HTN] Chest pain or angina

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
321318	Angina pectoris	194828000	SNOMED	NO	YES	NO
77670	Chest pain	29857009	SNOMED	NO	NO	NO

B.18 Chronic kidney disease

B.18.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Chronic kidney disease’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to with any of the following criteria:

having at least 1 condition occurrence of ‘[LEGEND HTN] Chronic kidney disease’, starting 30 days after cohort entry start date.
having at least 2 procedure occurrences of ‘[LEGEND HTN] Dialysis’, starting between 0 days before and all days after cohort entry start date.
having at least 2 observations of ‘[LEGEND HTN] Dialysis’, starting between 0 days before and all days after cohort entry start date.

B.18.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.18.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.18.4 Concept: [LEGEND HTN] Chronic kidney disease

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
194385	Aneurysm of renal artery	36184004	SNOMED	NO	YES	NO
45769152	Bartter syndrome	707742001	SNOMED	YES	YES	NO
46271022	Chronic kidney disease	709044004	SNOMED	NO	YES	NO
192279	Diabetic renal disease	127013003	SNOMED	NO	YES	NO
4263367	Glomerulonephritis	36171008	SNOMED	NO	YES	NO
261071	Glomerulosclerosis	197661001	SNOMED	NO	YES	NO
195289	Goodpasture’s syndrome	50581000	SNOMED	YES	YES	NO
195737	Hemorrhagic nephroso-nephritis	102455002	SNOMED	YES	YES	NO
201313	Hypertensive renal disease	38481006	SNOMED	NO	YES	NO
43530912	Induced termination of pregnancy complicated by renal failure	609452007	SNOMED	YES	YES	NO
4103224	Interstitial nephritis	28689008	SNOMED	NO	YES	NO
193253	Nephritis	52845002	SNOMED	NO	NO	NO
195314	Nephrotic syndrome	52254009	SNOMED	NO	YES	NO
4066005	Post-delivery acute renal failure with postnatal problem	200118004	SNOMED	YES	YES	NO
37116834	Postpartum acute renal failure	733839001	SNOMED	YES	YES	NO
195014	Renal failure following molar AND/OR ectopic pregnancy	43629001	SNOMED	YES	YES	NO
192359	Renal failure syndrome	42399005	SNOMED	NO	YES	NO
197930	Renal hypertension complicating pregnancy, childbirth and the puerperium	198949009	SNOMED	YES	YES	NO
197320	Acute renal failure syndrome	14669001	SNOMED	YES	YES	NO

B.18.5 Concept: [LEGEND HTN] Dialysis

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4090651	Dialysis finding	251859005	SNOMED	NO	YES	NO
4032243	Dialysis procedure	108241001	SNOMED	NO	YES	NO
45889365	Dialysis Services and Procedures	1012740	CPT4	NO	YES	NO

B.19 Cough

B.19.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Cough’.

B.19.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.19.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.19.4 Concept: [LEGEND HTN] Cough

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
254761	Cough	49727002	SNOMED	NO	YES	NO

B.20 Decreased libido

B.20.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Decreased libido’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.20.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.20.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.20.4 Concept: [LEGEND HTN] Decreased libido

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4087317	Lack of libido	248096004	SNOMED	NO	YES	NO
443262	Lack or loss of sexual desire	270903007	SNOMED	NO	YES	NO
436246	Reduced libido	8357008	SNOMED	NO	YES	NO

B.21 Dementia

B.21.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Dementia’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.21.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.21.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.21.4 Concept: [LEGEND HTN] Dementia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4182210	Dementia	52448006	SNOMED	NO	YES	NO
377788	General paresis - neurosyphilis	51928006	SNOMED	YES	YES	NO
372610	Postconcussion syndrome	40425004	SNOMED	YES	YES	NO
37116464	Dementia caused by heavy metal exposure	733184002	SNOMED	YES	YES	NO
4244346	Dialysis dementia	9345005	SNOMED	YES	YES	NO
37017247	Presenile dementia co-occurrent with human immunodeficiency virus infection	713488003	SNOMED	YES	YES	NO
37017549	Dementia co-occurrent with human immunodeficiency virus infection	713844000	SNOMED	YES	YES	NO

B.22 Depression

B.22.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Depression’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to with any of the following criteria:

having at least 1 condition occurrence of ‘[LEGEND HTN] Depression’, starting 1 days after cohort entry start date.
having at least 2 drug exposures of ‘[LEGEND HTN] Drugs to treat depression’, starting between 0 days before and all days after cohort entry start date; having no condition occurrences of ‘[LEGEND HTN] Other indications for drugs used to treat depression’, starting between 30 days before and 7 days after ‘[LEGEND HTN] Drugs to treat depression’ start date.
having at least 2 procedure occurrences of ‘[LEGEND HTN] Procedures for depression’, starting between 0 days before and all days after cohort entry start date.

B.22.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.22.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.22.4 Concept: [LEGEND HTN] Depression

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
442306	Adjustment disorder with depressed mood	57194009	SNOMED	NO	YES	NO
436665	Bipolar disorder	13746004	SNOMED	YES	YES	NO
440383	Depressive disorder	35489007	SNOMED	NO	YES	NO
4175329	Organic mood disorder of depressed type	42594001	SNOMED	NO	YES	NO

B.22.5 Concept: [LEGEND HTN] Drugs to treat depression

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
21604686	ANTIDEPRESSANTS	N06A	ATC	NO	YES	NO

B.22.6 Concept: [LEGEND HTN] Other indications for drugs used to treat depression

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
438407	Bulimia nervosa	78004001	SNOMED	NO	YES	NO
4311708	Diabetic peripheral neuropathy	424736006	SNOMED	NO	YES	NO
434613	Generalized anxiety disorder	21897009	SNOMED	NO	YES	NO
436962	Insomnia	193462001	SNOMED	NO	YES	NO
440374	Obsessive-compulsive disorder	191736004	SNOMED	NO	YES	NO
436074	Panic disorder	371631005	SNOMED	NO	YES	NO
436676	Posttraumatic stress disorder	47505003	SNOMED	NO	YES	NO
4242733	Premenstrual dysphoric disorder	596004	SNOMED	NO	YES	NO
440690	Social phobia	25501002	SNOMED	NO	YES	NO

B.22.7 Concept: [LEGEND HTN] Procedures for depression

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4030840	Electroconvulsive therapy	23835007	SNOMED	NO	YES	NO
2795842	Mental Health, Electroconvulsive Therapy	GZB	ICD10PCS	NO	YES	NO
2795675	Mental Health, Individual Psychotherapy	GZ5	ICD10PCS	NO	YES	NO
4327941	Psychotherapy	75516001	SNOMED	NO	YES	NO
45887951	Psychotherapy Services and Procedures	1021137	CPT4	NO	YES	NO

B.23 Diarrhea

B.23.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN} Diarrhea’.

B.23.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.23.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.23.4 Concept: [LEGEND HTN} Diarrhea

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
196523	Diarrhea	62315008	SNOMED	NO	YES	NO
4134607	Diarrheal disorder	128333008	SNOMED	NO	YES	NO
201773	Enteritis of small intestine	64613007	SNOMED	NO	NO	NO
80141	Functional diarrhea	47812002	SNOMED	NO	YES	NO
4207688	Infectious enteritis	55184003	SNOMED	NO	NO	NO
4324838	Noninfectious enteritis	71207007	SNOMED	NO	NO	NO
197596	Toxic gastroenteritis	71583005	SNOMED	NO	YES	NO
196620	Viral enteritis	78420004	SNOMED	NO	YES	NO

B.24 End stage renal disease

B.24.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] End stage renal disease’.

Restrict entry events to with any of the following criteria:

having at least 1 condition occurrence of ‘[LEGEND HTN] End stage renal disease’, starting between 1 days after and 90 days after cohort entry start date.
having at least 1 procedure occurrence of ‘[LEGEND HTN] Dialysis’, starting between 0 days after and 90 days after cohort entry start date.
having at least 1 observation of ‘[LEGEND HTN] Dialysis’, starting between 0 days after and 90 days after cohort entry start date.

Limit these restricted entry events to the earliest event per person.

B.24.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.24.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.24.4 Concept: [LEGEND HTN] End stage renal disease

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
443611	Chronic kidney disease stage 5	433146000	SNOMED	NO	YES	NO
193782	End stage renal disease	46177005	SNOMED	NO	YES	NO

B.24.5 Concept: [LEGEND HTN] Dialysis

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4090651	Dialysis finding	251859005	SNOMED	NO	YES	NO
4032243	Dialysis procedure	108241001	SNOMED	NO	YES	NO
45889365	Dialysis Services and Procedures	1012740	CPT4	NO	YES	NO

B.25 Fall

B.25.1 Cohort Entry Events

People enter the cohort when observing any of the following:

observations of ‘[LEGEND HTN] Falls’.

B.25.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.25.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.25.4 Concept: [LEGEND HTN] Falls

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
436583	Fall	1912002	SNOMED	NO	YES	NO

B.26 Gastrointestinal bleeding

B.26.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Gastrointestinal hemorrhage GI bleeding’.

B.26.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.26.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.26.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.26.5 Concept: [LEGEND HTN] Gastrointestinal hemorrhage GI bleeding

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4138962	Acute duodenal ulcer without hemorrhage AND without perforation	32490005	SNOMED	YES	YES	NO
4195231	Acute gastric ulcer without hemorrhage AND without perforation	67964002	SNOMED	YES	YES	NO
4147683	Acute gastrojejunal ulcer without hemorrhage AND without perforation	30514008	SNOMED	NO	NO	NO
4163865	Acute peptic ulcer without hemorrhage AND without perforation	45485004	SNOMED	YES	YES	NO
195584	Acute peptic ulcer without hemorrhage AND without perforation but with obstruction	58085004	SNOMED	YES	YES	NO
40482685	Angiodysplasia of duodenum	442267002	SNOMED	NO	YES	NO
28779	Bleeding esophageal varices	17709002	SNOMED	NO	YES	NO
4222896	Chronic duodenal ulcer without hemorrhage AND without perforation	40214005	SNOMED	YES	YES	NO
4296611	Chronic gastric ulcer without hemorrhage AND without perforation	76796008	SNOMED	YES	YES	NO
200769	Chronic gastric ulcer without hemorrhage, without perforation AND without obstruction	1567007	SNOMED	YES	YES	NO
4177387	Chronic gastrojejunal ulcer without hemorrhage AND without perforation	4269005	SNOMED	YES	YES	NO
434400	Chronic gastrojejunal ulcer without hemorrhage AND without perforation but with obstruction	56579005	SNOMED	YES	YES	NO
438795	Chronic gastrojejunal ulcer without hemorrhage, without perforation AND without obstruction	41626001	SNOMED	YES	YES	NO
4204555	Chronic peptic ulcer without hemorrhage AND without perforation	5492000	SNOMED	YES	YES	NO
24973	Chronic peptic ulcer without hemorrhage AND without perforation but with obstruction	12384004	SNOMED	YES	YES	NO
23808	Chronic peptic ulcer without hemorrhage, without perforation AND without obstruction	60400003	SNOMED	YES	YES	NO
2002608	Control of hemorrhage and suture of ulcer of stomach or duodenum	44.4	ICD9Proc	NO	YES	NO
198798	Dieulafoy’s vascular malformation	109558001	SNOMED	NO	YES	NO
4198381	Duodenal ulcer disease	51868009	SNOMED	NO	YES	NO
4209746	Duodenal ulcer without hemorrhage AND without perforation	56776001	SNOMED	YES	YES	NO
4112183	Esophageal varices with bleeding, associated with another disorder	195475003	SNOMED	NO	YES	NO
2108900	Esophagogastroduodenoscopy, flexible, transoral; with control of bleeding, any method	43255	CPT4	NO	YES	NO
2108878	Esophagoscopy, flexible, transoral; with control of bleeding, any method	43227	CPT4	NO	YES	NO
4265600	Gastric ulcer	397825006	SNOMED	NO	YES	NO
4248429	Gastric ulcer without hemorrhage AND without perforation	73481001	SNOMED	YES	YES	NO
192671	Gastrointestinal hemorrhage	74474003	SNOMED	NO	YES	NO
4101104	Gastrojejunal ulcer without hemorrhage AND without perforation	2783007	SNOMED	YES	YES	NO
443530	Hematochezia	405729008	SNOMED	YES	YES	NO
197925	Hemorrhage of rectum and anus	266464001	SNOMED	YES	YES	NO
4027663	Peptic ulcer	13200003	SNOMED	NO	YES	NO
4291028	Peptic ulcer without hemorrhage AND without perforation	37442009	SNOMED	YES	YES	NO

B.27 Genitourinary infection

B.27.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘UTI’.

Limit qualifying entry events to the earliest event per person.

B.27.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.27.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.27.4 Concept: UTI

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
81902	Urinary tract infectious disease	68566005	SNOMED	NO	YES	NO
4167328	Pyuria	4800001	SNOMED	NO	YES	NO
77340	Genitourinary tract infection in pregnancy	267204006	SNOMED	NO	YES	NO
4265485	Bacteriuria	61373006	SNOMED	NO	YES	NO
4126297	Chronic obstructive pyelonephritis	236379002	SNOMED	NO	YES	NO
195588	Cystitis	38822007	SNOMED	NO	YES	NO
198806	Abscess of prostate	8725005	SNOMED	YES	YES	NO
4126267	Chronic radiation cystitis	236629009	SNOMED	YES	YES	NO
194997	Prostatitis	9713002	SNOMED	YES	NO	NO
4077499	Sterile pyuria	275742001	SNOMED	YES	YES	NO
442345	Syphilis of kidney	59530001	SNOMED	YES	YES	NO
4062493	Mumps nephritis	17121006	SNOMED	YES	YES	NO
45757237	Diphtheria tubulointerstitial nephropathy	1086071000119103	SNOMED	YES	YES	NO
36714969	Asymptomatic bacteriuria	720406004	SNOMED	YES	YES	NO
195743	Diphtheritic cystitis	48278001	SNOMED	YES	YES	NO
201353	Irradiation cystitis	11251000	SNOMED	YES	YES	NO
4047937	Neonatal urinary tract infection	12301009	SNOMED	YES	YES	NO
201792	Nongonococcal urethritis	84619001	SNOMED	YES	YES	NO
4128384	Non-infective cystitis	236623005	SNOMED	YES	NO	NO
78357	Reactive arthritis triad	67224007	SNOMED	YES	YES	NO
195313	Urethral abscess	67277002	SNOMED	YES	YES	NO
197919	Urethral stricture due to infection	80375002	SNOMED	YES	YES	NO
439349	Cystitis associated with another disorder	197845000	SNOMED	YES	NO	NO
4227291	Hemorrhagic cystitis	87696004	SNOMED	YES	NO	NO
4060312	Infections of urethra in pregnancy	199206009	SNOMED	YES	NO	NO
4127564	Acute cystitis - culture-negative	236624004	SNOMED	YES	YES	NO
4126141	Chronic cystitis - culture negative	236626002	SNOMED	YES	NO	NO
4127565	Recurrent cystitis - culture-negative	236625003	SNOMED	YES	YES	NO
4207186	Viral infection by site	312130009	SNOMED	YES	YES	NO
4207190	Fungal infection by site	312146001	SNOMED	YES	YES	NO
434557	Tuberculosis	56717001	SNOMED	YES	YES	NO
432251	Disease caused by parasite	17322007	SNOMED	YES	YES	NO
36102152	Protozoal infectious disorders	10037072	MedDRA	YES	YES	NO
433417	Gonorrhea	15628003	SNOMED	YES	YES	NO
36102938	Chlamydial infections	10008561	MedDRA	YES	YES	NO

B.28 Gout

B.28.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Gout’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.28.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.28.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.28.4 Concept: [LEGEND HTN] Gout

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
440674	Gout	90560007	SNOMED	NO	YES	NO
4096347	Gouty arthropathy	190828008	SNOMED	NO	YES	NO
4128219	Urate nephropathy	236495001	SNOMED	NO	YES	NO
80070	Uric acid urolithiasis	267441009	SNOMED	NO	YES	NO

B.29 Headache

B.29.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Headache’.

B.29.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.29.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.29.4 Concept: [LEGEND HTN] Headache

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
378253	Headache	25064002	SNOMED	NO	YES	NO
375527	Headache disorder	230461009	SNOMED	NO	YES	NO

B.30 Hemorrhagic stroke

B.30.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] intracranial bleed Hemorrhagic stroke’.

B.30.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.30.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.30.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.30.5 Concept: [LEGEND HTN] intracranial bleed Hemorrhagic stroke

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
376713	Cerebral hemorrhage	274100004	SNOMED	NO	NO	NO
439847	Intracranial hemorrhage	1386000	SNOMED	NO	NO	NO
432923	Subarachnoid hemorrhage	21454007	SNOMED	NO	NO	NO

B.31 Hepatic failure

B.31.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] hepatic failure, necrosis or coma’.

Limit cohort entry events to the earliest event per person.

B.31.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.31.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.31.4 Concept: [LEGEND HTN] hepatic failure, necrosis or coma

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
377604	Hepatic coma	72836002	SNOMED	NO	NO	NO
4029488	Hepatic encephalopathy	13920009	SNOMED	NO	NO	NO
4245975	Hepatic failure	59927004	SNOMED	NO	YES	NO
4337543	Hepatic necrosis	87248009	SNOMED	NO	YES	NO

B.32 Hospitalization with heart failure

B.32.1 Cohort Entry Events

People enter the cohort when observing any of the following:

visit occurrences of ‘Inpatient or ER visit’; having at least 1 condition occurrence of ‘[LEGEND-HtnStepCare] Heart Failure’, starting between 0 days before and all days after ‘Inpatient or ER visit’ start date and starting anytime on or before ‘Inpatient or ER visit’ end date.

B.32.2 Cohort Exit

The cohort end date will be offset from index event’s end date plus 0 days.

B.32.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 7 days of each other.

B.32.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.32.5 Concept: [LEGEND-HtnStepCare] Heart Failure

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
315295	Congestive rheumatic heart failure	82523003	SNOMED	YES	YES	NO
316139	Heart failure	84114007	SNOMED	NO	YES	NO

B.33 Hyperkalemia

B.33.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Hyperkalemia’.
measurements of ‘[LEGEND HTN] Potassium measurement’, numeric value > 5.6; unit: “millimole per liter”.

B.33.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.33.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.33.4 Concept: [LEGEND HTN] Hyperkalemia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
434610	Hyperkalemia	14140009	SNOMED	NO	YES	NO

B.33.5 Concept: [LEGEND HTN] Potassium measurement

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
40789890	Potassium	Bld-Ser-Plas	LP42189-8	LOINC	NO	YES\|NO
4245152	Potassium measurement	59573005	SNOMED	NO	YES	NO
4276440	Potassium level - finding	365760004	SNOMED	NO	YES	NO

B.34 Hypoglycemia

B.34.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘Hypoglycemia’.

B.34.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.34.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.34.4 Concept: Hypoglycemia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
380688	Hypoglycemic coma	267384006	SNOMED	NO	YES	NO
4048805	Non-diabetic hypoglycemic coma	230796005	SNOMED	YES	YES	NO
4226798	Hypoglycemic coma due to diabetes mellitus	421725003	SNOMED	NO	YES	NO
4228112	Hypoglycemic coma due to type 1 diabetes mellitus	421437000	SNOMED	YES	YES	NO
36714116	Hypoglycemic coma due to type 2 diabetes mellitus	719216001	SNOMED	NO	YES	NO
24609	Hypoglycemia	302866003	SNOMED	NO	YES	NO
23034	Neonatal hypoglycemia	52767006	SNOMED	YES	YES	NO
4029424	Non-diabetic hypoglycemia	237637005	SNOMED	YES	YES	NO
4029423	Hypoglycemia due to diabetes mellitus	237633009	SNOMED	NO	YES	NO
45769876	Hypoglycemia due to type 1 diabetes mellitus	84371000119108	SNOMED	YES	YES	NO
45757363	Hypoglycemia due to type 2 diabetes mellitus	120731000119103	SNOMED	NO	YES	NO
4096804	Drug-induced hypoglycemia without coma	190448007	SNOMED	NO	YES	NO

B.35 Hypokalemia

B.35.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Hypokalemia’.

B.35.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.35.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.35.4 Concept: [LEGEND HTN] Hypokalemia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
45769152	Bartter syndrome	707742001	SNOMED	YES	YES	NO
437833	Hypokalemia	43339004	SNOMED	NO	YES	NO

B.36 Hypomagnesemia

B.36.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Hypomagnesemia’.

B.36.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.36.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.36.4 Concept: [LEGEND HTN] Hypomagnesemia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
438725	Disorder of magnesium metabolism	60853003	SNOMED	NO	YES	NO
4098604	Hypomagnesemia	190855004	SNOMED	NO	YES	NO

B.37 Hyponatremia

B.37.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Hyponatremia’.

B.37.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.37.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.37.4 Concept: [LEGEND HTN] Hyponatremia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
435515	Hypo-osmolality and or hyponatremia	267447008	SNOMED	NO	YES	NO
4232311	Hyponatremia	89627008	SNOMED	NO	YES	NO

B.38 Hypotension

B.38.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Hypotension’.

B.38.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.38.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.38.4 Concept: [LEGEND HTN] Hypotension

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
313232	Hemodialysis-associated hypotension	408667000	SNOMED	YES	YES	NO
317002	Low blood pressure	45007003	SNOMED	NO	YES	NO
314432	Maternal hypotension syndrome	88887003	SNOMED	YES	YES	NO

B.39 Impotence

B.39.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Impotence’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.39.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.39.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.39.4 Concept: [LEGEND HTN] Impotence

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4250163	Sexual arousal disorder	74007000	SNOMED	NO	YES	NO

B.40 Ischemic stroke

B.40.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Ischemic stroke’.

Restrict entry events to having at least 1 visit occurrence of ‘Inpatient or ER visit’, starting between all days before and 1 days after cohort entry start date and ending between 0 days before and all days after cohort entry start date.

B.40.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.40.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.40.4 Concept: [LEGEND HTN] Ischemic stroke

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
372924	Cerebral artery occlusion	20059004	SNOMED	NO	NO	NO
375557	Cerebral embolism	75543006	SNOMED	NO	NO	NO
443454	Cerebral infarction	432504007	SNOMED	NO	YES	NO
441874	Cerebral thrombosis	71444005	SNOMED	NO	NO	NO

B.40.5 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.41 Joint pain

B.41.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘Joint pain’.

B.41.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.41.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.41.4 Concept: Joint pain

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
77074	Joint pain	57676002	SNOMED	NO	NO	NO

B.42 Lower extremity amputation

B.42.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

procedure occurrences of ‘below-knee amputations’.

Restrict entry events to having no procedure occurrences of ‘below-knee amputations’, starting in the 30 days prior to cohort entry start date.

B.42.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 0 days.

B.42.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.42.4 Concept: below-knee amputations

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4264289	Amputation of ankle	397218006	SNOMED	NO	YES	NO
2006242	Amputation of ankle through malleoli of tibia and fibula	84.14	ICD9Proc	NO	YES	NO
2105446	Amputation, leg, through tibia and fibula	27880	CPT4	NO	YES	NO
2105804	Amputation, foot; midtarsal (eg, Chopart type procedure)	28800	CPT4	NO	YES	NO
2105805	Amputation, foot; transmetatarsal	28805	CPT4	NO	YES	NO
2105806	Amputation, metatarsal, with toe, single	28810	CPT4	NO	YES	NO
2105807	Amputation, toe; metatarsophalangeal joint	28820	CPT4	NO	YES	NO
2105808	Amputation, toe; interphalangeal joint	28825	CPT4	NO	YES	NO
2105451	Amputation, ankle, through malleoli of tibia and fibula (eg, Syme, Pirogoff type procedures), with plastic closure and resection of nerves	27888	CPT4	NO	YES	NO
2105447	Amputation, leg, through tibia and fibula; with immediate fitting technique including application of first cast	27881	CPT4	NO	YES	NO
4338257	Amputation of leg through tibia and fibula	88312006	SNOMED	NO	YES	NO
2105448	Amputation, leg, through tibia and fibula; open, circular (guillotine)	27882	CPT4	NO	YES	NO
4108565	Amputation of the foot	180030006	SNOMED	NO	YES	NO
2006229	Amputation of toe	84.11	ICD9Proc	NO	YES	NO
4159766	Amputation of toe	371186005	SNOMED	NO	YES	NO
4054983	Amputation through foot	211570009	SNOMED	NO	YES	NO
2006230	Amputation through foot	84.12	ICD9Proc	NO	YES	NO
4143797	Amputation through metatarsal bones	265739006	SNOMED	NO	YES	NO
2105450	Amputation, leg, through tibia and fibula; re-amputation	27886	CPT4	NO	YES	NO
2006231	Disarticulation of ankle	84.13	ICD9Proc	NO	YES	NO
2006244	Disarticulation of knee	84.16	ICD9Proc	NO	YES	NO
4018719	Midtarsal amputation of foot	209724005	SNOMED	NO	YES	NO
2006243	Other amputation below knee	84.15	ICD9Proc	NO	YES	NO
2105449	Amputation, leg, through tibia and fibula; secondary closure or scar revision	27884	CPT4	YES	YES	NO
4219032	Amputation of lower limb	397117006	SNOMED	NO	YES	NO

B.43 Malignant neoplasm

B.43.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Malignant neoplasms excluding non-melanoma skin cancer’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to with any of the following criteria:

having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of breast’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of prostate’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of lung’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of multiple myeloma’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of colon and rectum’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of bladder’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of lymphoma’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of ovary’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of thyroid’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of kidney’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of leukemia’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of brain’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of pancreas’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of liver’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant neoplasms of uterus’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Malignant melanoma’, starting between 0 days before and all days after cohort entry start date.
having at least 2 condition occurrences of ‘[LEGEND HTN] Myelodysplastic syndrome’, starting between 0 days before and all days after cohort entry start date.

B.43.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.43.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.43.4 Concept: [LEGEND HTN] Malignant neoplasms excluding non-melanoma skin cancer

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
443392	Malignant neoplastic disease	363346000	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.5 Concept: [LEGEND HTN] Malignant neoplasms of breast

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112853	Malignant tumor of breast	254837009	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO

B.43.6 Concept: [LEGEND HTN] Malignant neoplasms of prostate

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4163261	Malignant tumor of prostate	399068003	SNOMED	NO	YES	NO
200962	Primary malignant neoplasm of prostate	93974005	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.7 Concept: [LEGEND HTN] Malignant neoplasms of lung

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
443388	Malignant tumor of lung	363358000	SNOMED	NO	YES	NO
4311499	Primary malignant neoplasm of respiratory tract	93986008	SNOMED	NO	NO	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.8 Concept: [LEGEND HTN] Malignant neoplasms of multiple myeloma

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
437233	Multiple myeloma	109989006	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.9 Concept: [LEGEND HTN] Malignant neoplasms of colon and rectum

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4180790	Malignant tumor of colon	363406005	SNOMED	NO	YES	NO
443390	Malignant tumor of rectum	363351006	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.10 Concept: [LEGEND HTN] Malignant neoplasms of bladder

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
197508	Malignant tumor of urinary bladder	399326009	SNOMED	NO	YES	NO
196360	Primary malignant neoplasm of bladder	93689003	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.11 Concept: [LEGEND HTN] Malignant neoplasms of lymphoma

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4082311	B-cell chronic lymphocytic leukemia	277473004	SNOMED	YES	YES	NO
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
432571	Malignant lymphoma	118600007	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.12 Concept: [LEGEND HTN] Malignant neoplasms of ovary

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4181351	Malignant tumor of ovary	363443007	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.13 Concept: [LEGEND HTN] Malignant neoplasms of thyroid

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4181483	Malignant tumor of parathyroid gland	363481002	SNOMED	NO	YES	NO
4178976	Malignant tumor of thyroid gland	363478007	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.14 Concept: [LEGEND HTN] Malignant neoplasms of kidney

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
196653	Malignant tumor of kidney	363518003	SNOMED	NO	YES	NO
198985	Primary malignant neoplasm of kidney	93849006	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.15 Concept: [LEGEND HTN] Malignant neoplasms of leukemia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
317510	Leukemia	93143009	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.16 Concept: [LEGEND HTN] Malignant neoplasms of brain

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
443588	Malignant neoplasm of brain	428061005	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.17 Concept: [LEGEND HTN] Malignant neoplasms of pancreas

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4180793	Malignant tumor of pancreas	363418001	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.18 Concept: [LEGEND HTN] Malignant neoplasms of liver

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4246127	Malignant neoplasm of liver	93870000	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.19 Concept: [LEGEND HTN] Malignant neoplasms of uterus

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
197230	Malignant neoplasm of uterus	371973000	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.20 Concept: [LEGEND HTN] Malignant melanoma

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4112752	Basal cell carcinoma of skin	254701007	SNOMED	YES	YES	NO
4162276	Malignant melanoma	372244006	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO
4111921	Squamous cell carcinoma of skin	254651007	SNOMED	YES	YES	NO

B.43.21 Concept: [LEGEND HTN] Myelodysplastic syndrome

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
138994	Myelodysplastic syndrome	109995007	SNOMED	NO	YES	NO
432851	Secondary malignant neoplastic disease	128462008	SNOMED	YES	YES	NO

B.44 Measured renal dysfunction

B.44.1 Cohort Entry Events

People enter the cohort when observing any of the following:

measurements of ‘Creatinine measurement’, numeric value > 3; unit: “milligram per deciliter”.
measurements of ‘Creatinine measurement’, numeric value > 265; unit: “micromole/liter”.
measurements of ‘Creatinine measurement’, numeric value > 0.265; unit: “millimole per liter”.
measurements of ‘Creatinine measurement’, numeric value > 3; unit: “milligram”.

Limit cohort entry events to the earliest event per person.

B.44.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.44.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.44.4 Concept: Creatinine measurement

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
3016723	Creatinine [Mass/volume] in Serum or Plasma	2160-0	LOINC	NO	YES	NO
3022243	Creatinine [Mass/volume] in Serum or Plasma –pre dialysis	11042-9	LOINC	NO	YES	NO
3020564	Creatinine [Moles/volume] in Serum or Plasma	14682-9	LOINC	NO	YES	NO

B.45 Nausea

B.45.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Nausea’.

B.45.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.45.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.45.4 Concept: [LEGEND HTN] Nausea

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
30284	Motion sickness	37031009	SNOMED	YES	YES	NO
31967	Nausea	422587007	SNOMED	NO	YES	NO

B.46 Neutropenia or agranulocytosis

B.46.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Neutropenia and agranulocytosis’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.46.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.46.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.46.4 Concept: [LEGEND HTN] Neutropenia and agranulocytosis

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4150156	Agranulocytopenic disorder	267538002	SNOMED	NO	NO	NO
440689	Agranulocytosis	17182001	SNOMED	NO	NO	NO
4322386	Chemotherapy-induced neutropenia	425229001	SNOMED	NO	NO	NO
4174297	Chloramphenicol-induced neutropenia	276628009	SNOMED	NO	NO	NO
4211401	Dose-related drug-induced neutropenia	56918001	SNOMED	NO	NO	NO
432289	Drug-induced neutropenia	47318007	SNOMED	NO	NO	NO
320073	Neutropenia	165517008	SNOMED	NO	NO	NO
4119158	Neutropenic disorder	303011007	SNOMED	NO	NO	NO
4190716	Non dose-related drug-induced neutropenia	3902000	SNOMED	NO	NO	NO
4135712	Toxic neutropenia	32092008	SNOMED	NO	NO	NO

B.47 Peripheral edema

B.47.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Edema’.

B.47.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.47.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.47.4 Concept: [LEGEND HTN] Edema

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
433595	Edema	267038008	SNOMED	NO	NO	NO
4155910	Edema, generalized	271808008	SNOMED	NO	YES	NO
4171917	Localized edema	274724004	SNOMED	NO	YES	NO
133299	Swelling of limb	80068009	SNOMED	NO	YES	NO

B.48 Photosensitivity

B.48.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘Photosensitivity’.

B.48.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.48.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.48.4 Concept: Photosensitivity

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4300445	Acantholytic actinic keratosis	403199007	SNOMED	YES	NO	NO
4263325	Actinic cheilitis	46795000	SNOMED	YES	NO	NO
4031007	Actinic folliculitis	238529007	SNOMED	YES	NO	NO
442179	Actinic granuloma	79144000	SNOMED	YES	NO	NO
37312586	Actinic intraepidermal squamous cell carcinoma	789051005	SNOMED	YES	NO	NO
138825	Actinic keratosis	201101007	SNOMED	YES	NO	NO
4304266	Actinic keratosis of eyelid	418686001	SNOMED	YES	NO	NO
4064057	Actinic lichen planus	200999007	SNOMED	YES	NO	NO
141374	Actinic prurigo	201015007	SNOMED	YES	NO	NO
4031006	Actinic reaction	238528004	SNOMED	YES	NO	NO
439096	Actinic reticuloid	52636001	SNOMED	YES	NO	NO
4070156	Acute actinic otitis externa	21543000	SNOMED	YES	NO	NO
4290728	Acute effect of ultraviolet radiation on normal skin	402165001	SNOMED	YES	NO	NO
4241471	Acute phytophotodermatitis	58306008	SNOMED	YES	NO	NO
36674412	Ataxia, photosensitivity, short stature syndrome	773769008	SNOMED	YES	NO	NO
4293437	Atrophic actinic keratosis	403200005	SNOMED	YES	NO	NO
4066470	Berloque dermatitis	200836002	SNOMED	YES	NO	NO
4119822	Bowenoid actinic keratosis	304524009	SNOMED	YES	NO	NO
4033832	Brachioradial summer pruritus	109252001	SNOMED	YES	NO	NO
37116482	Burn of skin caused by exposure to artificial source of ultraviolet radiation	733209003	SNOMED	YES	NO	NO
37116483	Burn of skin caused by ultraviolet radiation due to ultraviolet light therapy	733210008	SNOMED	YES	NO	NO
4290729	Chronic effect of ultraviolet radiation on normal skin (photo-aging)	402166000	SNOMED	YES	NO	NO
4239682	Chronic phototoxic dermatitis	69231004	SNOMED	YES	NO	NO
4242265	Chronic phytophotodermatitis	58419006	SNOMED	YES	NO	NO
36715275	Cutaneous photosensitivity and lethal colitis syndrome	720820000	SNOMED	YES	NO	NO
4230340	Cutis rhomboidalis nuchae	89019003	SNOMED	YES	NO	NO
4300796	Diffuse actinic hyperkeratosis	403208003	SNOMED	YES	NO	NO
141650	Disseminated superficial actinic porokeratosis	41495000	SNOMED	YES	NO	NO
4301164	Drug-induced pellagra	403626007	SNOMED	YES	NO	NO
4299673	Familial actinic prurigo of lip	403210001	SNOMED	YES	NO	NO
4234867	Food-induced photosensitivity	90386003	SNOMED	YES	NO	NO
36715367	Hair defect with photosensitivity and intellectual disability syndrome	721007005	SNOMED	YES	NO	NO
4308081	Hydroa vacciniforme	200837006	SNOMED	YES	NO	NO
42709861	Hyperkeratotic actinic keratosis	449733007	SNOMED	YES	NO	NO
4112749	Hypertrophic solar keratosis	254667001	SNOMED	YES	NO	NO
4300444	Idiopathic photo-onycholysis	403196000	SNOMED	YES	NO	NO
4031005	Juvenile spring eruption	238526000	SNOMED	YES	NO	NO
4116197	Lentigo maligna	302836005	SNOMED	YES	NO	NO
4299672	Lichenoid actinic keratosis	403198004	SNOMED	YES	NO	NO
4080922	Light - exacerbated acne	238530002	SNOMED	YES	NO	NO
4293560	Multiple actinic keratoses	403202002	SNOMED	YES	NO	NO
4293562	Multiple actinic keratoses involving face	403204001	SNOMED	YES	NO	NO
4300794	Multiple actinic keratoses involving forehead and temples	403205000	SNOMED	YES	NO	NO
4300795	Multiple actinic keratoses involving hands	403206004	SNOMED	YES	NO	NO
4293563	Multiple actinic keratoses involving legs	403207008	SNOMED	YES	NO	NO
4293561	Multiple actinic keratoses involving scalp	403203007	SNOMED	YES	NO	NO
37110331	Neonatal burn due to phototherapy caused by ultraviolet radiation	724551009	SNOMED	YES	NO	NO
4006157	Nodular elastosis with cysts and comedones	111200005	SNOMED	YES	NO	NO
37110590	Occupational phototoxic reaction to skin contact with exogenous photoactive agent	724873006	SNOMED	YES	NO	NO
4292224	Photoaggravated psoriasis	402318000	SNOMED	YES	NO	NO
4293593	Photoaggravated rosacea	403365004	SNOMED	YES	NO	NO
4290732	Photoaggravation of disorder	402179009	SNOMED	YES	NO	NO
42537710	Photodermatitis co-occurrent and due to autoimmune disease	737249005	SNOMED	YES	NO	NO
4318376	Photoonycholysis	95342006	SNOMED	YES	NO	NO
4234104	Photosensitivity	90128006	SNOMED	NO	YES	NO
42537712	Phototoxic reaction of skin caused by cosmetic	737251009	SNOMED	YES	NO	NO
42537711	Phototoxic reaction of skin caused by fragrance	737250005	SNOMED	YES	NO	NO
4290730	Phototoxic reaction to dye	402174004	SNOMED	YES	NO	NO
4298594	Phototoxic reaction to tar or derivative	402175003	SNOMED	YES	NO	NO
4298593	Phototoxic reaction to topical chemical	402173005	SNOMED	YES	NO	NO
4270722	Phototoxic reaction to topically applied medicament	402176002	SNOMED	YES	NO	NO
42539382	Pigmentation of skin caused by artificial ultraviolet light	762664003	SNOMED	YES	NO	NO
42709860	Pigmented actinic keratosis	449732002	SNOMED	YES	NO	NO
4080921	Polymorphous light eruption	238525001	SNOMED	YES	NO	NO
4176424	Polymorphous light eruption, diffuse erythematous type	51048002	SNOMED	YES	NO	NO
4223992	Polymorphous light eruption, eczematous type	84036008	SNOMED	YES	NO	NO
4204365	Polymorphous light eruption, papular type	54116000	SNOMED	YES	NO	NO
4195589	Polymorphous light eruption, papulovesicular type	79372000	SNOMED	YES	NO	NO
4278846	Polymorphous light eruption, plaque type	6618004	SNOMED	YES	NO	NO
4297664	Porphyria-induced phototoxic burn	402480004	SNOMED	YES	NO	NO
4296207	Proliferative actinic keratosis	403201009	SNOMED	YES	NO	NO
4066838	Pruritus estivalis	201024003	SNOMED	YES	NO	NO
4031625	Solar comedone	238518008	SNOMED	YES	NO	NO
4185267	Solar degeneration	43982006	SNOMED	YES	NO	NO
4031162	Solar lentiginosis	238712007	SNOMED	YES	NO	NO
4217502	Solar lentigo	72100002	SNOMED	YES	NO	NO
4296189	Solar pruritus	402177006	SNOMED	YES	NO	NO
4033831	Solar pruritus of elbows	109251008	SNOMED	YES	NO	NO
4031004	Strimmer dermatitis	238522003	SNOMED	YES	NO	NO
4296206	Sun-induced wrinkles	403197009	SNOMED	YES	NO	NO

B.49 Rash

B.49.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Rash’.

B.49.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.49.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.49.4 Concept: [LEGEND HTN] Rash

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
140214	Eruption	271807003	SNOMED	NO	YES	NO
139900	Urticaria	126485001	SNOMED	NO	YES	NO

B.50 Revascularization

B.50.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

procedure occurrences of ‘PCI’.
procedure occurrences of ‘CABG’.

B.50.2 Additional Inclusion Criteria

I. Hospitalization

Entry events having at least 1 visit occurrence of ‘Hospitalization’, starting between 0 days before and 0 days after cohort entry start date.

B.50.3 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.50.4 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.50.5 Concept: PCI

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4006788	Percutaneous transluminal coronary angioplasty	11101003	SNOMED	NO	YES	NO
4264285	Percutaneous transluminal coronary angioplasty by rotoablation	397193006	SNOMED	NO	YES	NO
4265293	Percutaneous transluminal coronary angioplasty with rotoablation, single vessel	397431004	SNOMED	NO	YES	NO
4225903	Percutaneous transluminal coronary angioplasty, multiple vessels	85053006	SNOMED	NO	YES	NO
4283892	Placement of stent in coronary artery	36969009	SNOMED	NO	YES	NO
4337738	Percutaneous endarterectomy of coronary artery	232726007	SNOMED	NO	YES	NO
4139198	Percutaneous transluminal thrombolysis of artery	426485003	SNOMED	NO	YES	NO
44511532	Percutaneous transluminal thrombolysis of artery	L71.6	OPCS4	NO	YES	NO
45770795	Percutaneous transluminal balloon angioplasty and insertion of drug eluting stent into coronary artery	936451000000108	SNOMED	NO	YES	NO
44789455	Insertion of drug-eluting coronary artery stent	203741000000101	SNOMED	NO	NO	NO
44784573	Percutaneous transluminal atherectomy of coronary artery by rotary cutter using fluoroscopic guidance	698740005	SNOMED	NO	YES	NO
44512256	Percutaneous transluminal arterial thrombolysis and reconstruction	L66.1	OPCS4	NO	YES	NO
44511273	Unspecified percutaneous transluminal balloon angioplasty and insertion of stent into coronary artery	K75.9	OPCS4	NO	YES	NO
44511272	Other specified percutaneous transluminal balloon angioplasty and insertion of stent into coronary artery	K75.8	OPCS4	NO	NO	NO
44511271	Percutaneous transluminal balloon angioplasty and insertion of 3 or more stents into coronary artery NEC	K75.4	OPCS4	NO	YES	NO
44511269	Percutaneous transluminal balloon angioplasty and insertion of 3 or more drug-eluting stents into coronary artery	K75.2	OPCS4	NO	YES	NO
44511268	Percutaneous transluminal balloon angioplasty and insertion of 1-2 drug-eluting stents into coronary artery	K75.1	OPCS4	NO	YES	NO
44511133	Other specified transluminal balloon angioplasty of coronary artery	K49.8	OPCS4	NO	NO	NO
44511131	Percutaneous transluminal balloon angioplasty of bypass graft of coronary artery	K49.3	OPCS4	NO	YES	NO
44511130	Percutaneous transluminal balloon angioplasty of multiple coronary arteries	K49.2	OPCS4	NO	YES	NO
43533353	Percutaneous transluminal coronary atherectomy, with drug eluting intracoronary stent, with coronary angioplasty when performed; single major coronary artery or branch	C9602	HCPCS	NO	YES	NO
43533352	Percutaneous transcatheter placement of drug-eluting intracoronary stent(s), with coronary angioplasty when performed; each additional branch of a major coronary artery (list separately in addition to code for primary procedure)	C9601	HCPCS	NO	NO	NO
43533248	Percutaneous transluminal coronary atherectomy, with drug-eluting intracoronary stent, with coronary angioplasty when performed; each additional branch of a major coronary artery (list separately in addition to code for primary procedure)	C9603	HCPCS	NO	YES	NO
43533247	Percutaneous transcatheter placement of drug eluting intracoronary stent(s), with coronary angioplasty when performed; single major coronary artery or branch	C9600	HCPCS	NO	NO	NO
43531440	Percutaneous transluminal insertion of metal stent into coronary artery using fluoroscopic guidance	609154002	SNOMED	NO	YES	NO
43531439	Percutaneous insertion of drug eluting stent into coronary artery using fluoroscopic guidance	609153008	SNOMED	NO	NO	NO
43531438	Percutaneous insertion of stent into aneurysm of coronary artery using fluoroscopic guidance	609152003	SNOMED	NO	NO	NO
4329263	Placement of stent in circumflex branch of left coronary artery	429499003	SNOMED	NO	YES	NO
4328103	Infusion of intra-arterial thrombolytic agent with percutaneous transluminal coronary angioplasty	75761004	SNOMED	NO	NO	NO
4264286	Percutaneous rotational coronary endarterectomy	397194000	SNOMED	NO	NO	NO
4238755	Infusion of intra-arterial thrombolytic agent with percutaneous transluminal coronary angioplasty, single vessel	91338001	SNOMED	NO	NO	NO
4216356	Infusion of intra-arterial thrombolytic agent with percutaneous transluminal coronary angioplasty, multiple vessels	80762004	SNOMED	NO	NO	NO
4214516	Insertion of drug coated stent	414509005	SNOMED	NO	NO	NO
4181025	Percutaneous transluminal balloon angioplasty with insertion of stent into coronary artery	429639007	SNOMED	NO	YES	NO
4178148	Placement of stent in anterior descending branch of left coronary artery	428488008	SNOMED	NO	YES	NO
4175997	Percutaneous transluminal thrombolysis and reconstruction of artery	428068004	SNOMED	NO	YES	NO
4171077	Fluoroscopic angiography of coronary artery and insertion of stent	418982001	SNOMED	NO	NO	NO
4020653	Percutaneous transluminal balloon angioplasty of bypass graft of coronary artery	175066001	SNOMED	NO	YES	NO
2001506	Insertion of drug-eluting coronary artery stent(s)	36.07	ICD9Proc	NO	NO	NO
2001505	Insertion of non-drug-eluting coronary artery stent(s)	36.06	ICD9Proc	NO	NO	NO
2000064	Percutaneous transluminal coronary angioplasty [PTCA]	00.66	ICD9Proc	NO	YES	NO
2001500	Single vessel percutaneous transluminal coronary angioplasty [PTCA] or coronary atherectomy without mention of thrombolytic agent	36.01	ICD9Proc	NO	YES	NO
2001504	Multiple vessel percutaneous transluminal coronary angioplasty [PTCA] or coronary atherectomy performed during the same operation, with or without mention of thrombolytic agent	36.05	ICD9Proc	NO	NO	NO
2001501	Single vessel percutaneous transluminal coronary angioplasty [PTCA] or coronary atherectomy with mention of thrombolytic agent	36.02	ICD9Proc	NO	YES	NO

B.50.6 Concept: Hospitalization

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.50.7 Concept: CABG

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
2001516	Abdominal-coronary artery bypass	36.17	ICD9Proc	NO	YES	NO
4284104	Aortocoronary artery bypass graft	67166004	SNOMED	NO	YES	NO
4229433	Aortocoronary artery bypass graft with prosthesis	8876004	SNOMED	NO	YES	NO
4146972	Aortocoronary artery bypass graft with saphenous vein graft	3546002	SNOMED	NO	YES	NO
4228305	Aortocoronary artery bypass graft with three vein grafts	405599002	SNOMED	NO	YES	NO
4228304	Aortocoronary artery bypass graft with two vein grafts	405598005	SNOMED	NO	YES	NO
4063237	Aortocoronary artery bypass graft with vein graft	17073005	SNOMED	NO	YES	NO
4148030	Aortocoronary bypass grafting	309814006	SNOMED	NO	YES	NO
4008625	Aortocoronary bypass of four or more coronary arteries	10190003	SNOMED	NO	YES	NO
4106548	Aortocoronary bypass of one coronary artery	29819009	SNOMED	NO	YES	NO
4031996	Aortocoronary bypass of three coronary arteries	14323007	SNOMED	NO	YES	NO
4234990	Aortocoronary bypass of two coronary arteries	90487008	SNOMED	NO	YES	NO
45889469	Arterial Grafting for Coronary Artery Bypass	1006216	CPT4	NO	YES	NO
4240486	Carotid-subclavian artery bypass graft with vein	59012002	SNOMED	NO	YES	NO
4336464	Coronary artery bypass graft	232717009	SNOMED	NO	YES	NO
4337056	Coronary artery bypass graft x 1	232719007	SNOMED	NO	YES	NO
4000733	Coronary artery bypass graft, anastomosis of artery of thorax to coronary artery	119565001	SNOMED	NO	YES	NO
4336467	Coronary artery bypass grafts greater than 5	232724005	SNOMED	NO	YES	NO
4336465	Coronary artery bypass grafts x 2	232720001	SNOMED	NO	YES	NO
4339629	Coronary artery bypass grafts x 3	232721002	SNOMED	NO	YES	NO
4337737	Coronary artery bypass grafts x 4	232722009	SNOMED	NO	YES	NO
4336466	Coronary artery bypass grafts x 5	232723004	SNOMED	NO	YES	NO
4233421	Coronary artery bypass with autogenous graft of internal mammary artery, single graft	359601003	SNOMED	NO	YES	NO
4305509	Coronary artery bypass with autogenous graft, five grafts	82247006	SNOMED	NO	YES	NO
4309432	Coronary artery bypass with autogenous graft, four grafts	39202005	SNOMED	NO	YES	NO
4011931	Coronary artery bypass with autogenous graft, three grafts	10326007	SNOMED	NO	YES	NO
4253805	Coronary artery bypass with autogenous graft, two grafts	74371005	SNOMED	NO	YES	NO
45887879	Coronary artery bypass, using arterial graft(s)	1006217	CPT4	NO	YES	NO
2107242	Coronary artery bypass, using arterial graft(s); 2 coronary arterial grafts	33534	CPT4	NO	YES	NO
2107243	Coronary artery bypass, using arterial graft(s); 3 coronary arterial grafts	33535	CPT4	NO	YES	NO
2107244	Coronary artery bypass, using arterial graft(s); 4 or more coronary arterial grafts	33536	CPT4	NO	YES	NO
2107231	Coronary artery bypass, using arterial graft(s); single arterial graft	33533	CPT4	NO	YES	NO
45889898	Coronary artery bypass, using venous graft(s) and arterial graft(s)	1006208	CPT4	NO	YES	NO
2107223	Coronary artery bypass, using venous graft(s) and arterial graft(s); 2 venous grafts (List separately in addition to code for primary procedure)	33518	CPT4	NO	YES	NO
2107224	Coronary artery bypass, using venous graft(s) and arterial graft(s); 3 venous grafts (List separately in addition to code for primary procedure)	33519	CPT4	NO	YES	NO
2107226	Coronary artery bypass, using venous graft(s) and arterial graft(s); 4 venous grafts (List separately in addition to code for primary procedure)	33521	CPT4	NO	YES	NO
2107227	Coronary artery bypass, using venous graft(s) and arterial graft(s); 5 venous grafts (List separately in addition to code for primary procedure)	33522	CPT4	NO	YES	NO
2107228	Coronary artery bypass, using venous graft(s) and arterial graft(s); 6 or more venous grafts (List separately in addition to code for primary procedure)	33523	CPT4	NO	YES	NO
2107222	Coronary artery bypass, using venous graft(s) and arterial graft(s); single vein graft (List separately in addition to code for primary procedure)	33517	CPT4	NO	YES	NO
45887862	Coronary artery bypass, vein only	1006200	CPT4	NO	YES	NO
2107217	Coronary artery bypass, vein only; 2 coronary venous grafts	33511	CPT4	NO	YES	NO
2107218	Coronary artery bypass, vein only; 3 coronary venous grafts	33512	CPT4	NO	YES	NO
2107219	Coronary artery bypass, vein only; 4 coronary venous grafts	33513	CPT4	NO	YES	NO
2107220	Coronary artery bypass, vein only; 5 coronary venous grafts	33514	CPT4	NO	YES	NO
2107221	Coronary artery bypass, vein only; 6 or more coronary venous grafts	33516	CPT4	NO	YES	NO
2107216	Coronary artery bypass, vein only; single coronary venous graft	33510	CPT4	NO	YES	NO
2001515	Double internal mammary-coronary artery bypass	36.16	ICD9Proc	NO	YES	NO
4000732	Internal mammary-coronary artery bypass graft	119564002	SNOMED	NO	YES	NO
2001514	Single internal mammary-coronary artery bypass	36.15	ICD9Proc	NO	YES	NO
4233420	Single internal mammary-coronary artery bypass	359597003	SNOMED	NO	YES	NO
45889467	Venous Grafting Only for Coronary Artery Bypass	1006199	CPT4	NO	YES	NO
4020216	Revision of bypass for coronary artery	175036008	SNOMED	NO	NO	NO
4305852	Off-pump coronary artery bypass	418824004	SNOMED	NO	NO	NO

B.51 Rhabdomyolysis

B.51.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Rhabdomyolysis narrow’.
condition occurrences of ‘[LEGEND HTN] Rhabdomyolysis broad’; having at least 1 measurement of ‘[LEGEND HTN] Rhabdomyolysis measurement of creatine kinase’, starting between 7 days before and 7 days after ‘[LEGEND HTN] Rhabdomyolysis broad’ start date; numeric value > 0; high range-to-value ratio > 5.

B.51.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.51.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 90 days of each other.

B.51.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.51.5 Concept: [LEGEND HTN] Rhabdomyolysis narrow

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
439142	Myoglobinuria	48165008	SNOMED	NO	YES	NO
4345578	Rhabdomyolysis	240131006	SNOMED	NO	YES	NO

B.51.6 Concept: [LEGEND HTN] Rhabdomyolysis broad

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
137967	Muscle, ligament and fascia disorders	268006001	SNOMED	NO	NO	NO
439142	Myoglobinuria	48165008	SNOMED	NO	YES	NO
4345578	Rhabdomyolysis	240131006	SNOMED	NO	YES	NO

B.51.7 Concept: [LEGEND HTN] Rhabdomyolysis measurement of creatine kinase

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
40782593	Creatine kinase	LP15510-8	LOINC	NO	YES	NO
4265595	Creatine kinase measurement	397798009	SNOMED	NO	YES	NO

B.52 Stroke

B.52.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND-HtnStepCare] Stroke (ischemic or hemorrhagic)’.

B.52.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.52.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.52.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.52.5 Concept: [LEGEND-HtnStepCare] Stroke (ischemic or hemorrhagic)

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
372924	Cerebral artery occlusion	20059004	SNOMED	NO	NO	NO
375557	Cerebral embolism	75543006	SNOMED	NO	NO	NO
376713	Cerebral hemorrhage	274100004	SNOMED	NO	NO	NO
443454	Cerebral infarction	432504007	SNOMED	NO	YES	NO
441874	Cerebral thrombosis	71444005	SNOMED	NO	NO	NO
439847	Intracranial hemorrhage	1386000	SNOMED	NO	NO	NO
432923	Subarachnoid hemorrhage	21454007	SNOMED	NO	NO	NO
43530727	Spontaneous cerebral hemorrhage	291571000119106	SNOMED	NO	NO	NO
4148906	Spontaneous subarachnoid hemorrhage	270907008	SNOMED	NO	NO	NO

B.53 Sudden cardiac death

B.53.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Sudden cardiac death’.

B.53.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.53.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.53.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.53.5 Concept: [LEGEND HTN] Sudden cardiac death

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4048809	Brainstem death	230802007	SNOMED	NO	YES	NO
321042	Cardiac arrest	410429000	SNOMED	NO	YES	NO
442289	Death in less than 24 hours from onset of symptoms	53559009	SNOMED	NO	YES	NO
4317150	Sudden cardiac death	95281009	SNOMED	NO	YES	NO
4132309	Sudden death	26636000	SNOMED	NO	YES	NO
437894	Ventricular fibrillation	71908006	SNOMED	YES	YES	NO

B.54 Syncope

B.54.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Syncope’.

B.54.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.54.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.54.4 Concept: [LEGEND HTN] Syncope

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
140586	Heat syncope	89797005	SNOMED	YES	YES	NO
135360	Syncope	271594007	SNOMED	NO	YES	NO
38001140	Syncope & collapse	312	DRG	NO	NO	NO

B.55 Thrombocytopenia

B.55.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Thrombocytopenia’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.55.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.55.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.55.4 Concept: [LEGEND HTN] Thrombocytopenia

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
432870	Thrombocytopenic disorder	302215000	SNOMED	NO	YES	NO

B.56 Transient ischemic attack

B.56.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Transient ischemic attack (TIA) Transient cerebral Ischemia (TCA)’.

B.56.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 7 days.

B.56.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.56.4 Concept: Inpatient or ER visit

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
262	Emergency Room and Inpatient Visit	ERIP	Visit	NO	YES	NO
9203	Emergency Room Visit	ER	Visit	NO	YES	NO
9201	Inpatient Visit	IP	Visit	NO	YES	NO

B.56.5 Concept: [LEGEND HTN] Transient ischemic attack (TIA) Transient cerebral Ischemia (TCA)

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
373503	Transient cerebral ischemia	266257000	SNOMED	NO	YES	NO

B.57 Type 2 diabetes mellitus

B.57.1 Cohort Entry Events

People may enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Type 2 Diabetes Mellitus’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

Restrict entry events to with any of the following criteria:

having at least 1 condition occurrence of ‘[LEGEND HTN] Type 2 Diabetes Mellitus’, starting 1 days after cohort entry start date.
having at least 2 drug exposures of ‘[LEGEND HTN] Drugs to treat Type 2 Diabetes Mellitus excluding insulin’, starting between 0 days before and all days after cohort entry start date.
having at least 2 measurements of ‘[LEGEND HTN] Hemoglobin A1c measurement’, starting 7 days before cohort entry start date; numeric value between 6.5 and 30; unit: “percent”.

B.57.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.57.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.57.4 Concept: [LEGEND HTN] Type 2 Diabetes Mellitus

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
443735	Coma associated with diabetes mellitus	420662003	SNOMED	NO	YES	NO
4225656	Diabetic cataract associated with type 1 diabetes mellitus	421920002	SNOMED	YES	YES	NO
443767	Diabetic oculopathy	25093002	SNOMED	NO	YES	NO
192279	Diabetic renal disease	127013003	SNOMED	NO	YES	NO
4227210	Diabetic retinopathy associated with type 1 diabetes mellitus	420789003	SNOMED	YES	YES	NO
435216	Disorder due to type 1 diabetes mellitus	420868002	SNOMED	YES	YES	NO
443732	Disorder due to type 2 diabetes mellitus	422014003	SNOMED	NO	YES	NO
37016355	Hyperosmolar coma due to secondary diabetes mellitus	368601000119102	SNOMED	YES	YES	NO
4228112	Hypoglycemic coma in type 1 diabetes mellitus	421437000	SNOMED	YES	YES	NO
4224254	Ketoacidotic coma in type 1 diabetes mellitus	421075007	SNOMED	YES	YES	NO
376065	Neurologic disorder associated with type 2 diabetes mellitus	421326000	SNOMED	NO	YES	NO
443729	Peripheral circulatory disorder associated with type 2 diabetes mellitus	422166005	SNOMED	NO	YES	NO
200687	Renal disorder associated with type 1 diabetes mellitus	421893009	SNOMED	YES	YES	NO
201254	Type 1 diabetes mellitus	46635009	SNOMED	YES	YES	NO
201531	Type 1 diabetes mellitus with hyperosmolar coma	190330002	SNOMED	YES	YES	NO
4295011	Type 1 diabetes mellitus with persistent microalbuminuria	401110002	SNOMED	YES	YES	NO
201826	Type 2 diabetes mellitus	44054006	SNOMED	NO	YES	NO

B.57.5 Concept: [LEGEND HTN] Drugs to treat Type 2 Diabetes Mellitus excluding insulin

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
21600744	BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS	A10B	ATC	NO	YES	NO

B.57.6 Concept: [LEGEND HTN] Hemoglobin A1c measurement

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
4197971	HbA1c measurement	313835008	SNOMED	NO	NO	NO
44786901	HEDIS 2014 Value Set - HbA1c Tests	74246-0	LOINC	NO	NO	NO
3004410	Hemoglobin A1c (Glycated)	4548-4	LOINC	NO	NO	NO
3034639	Hemoglobin A1c [Mass/volume] in Blood	41995-2	LOINC	NO	NO	NO
40758583	Hemoglobin A1c in Blood	55454-3	LOINC	NO	NO	NO
3007263	Hemoglobin A1c/Hemoglobin.total in Blood by calculation	17855-8	LOINC	NO	NO	NO
3003309	Hemoglobin A1c/Hemoglobin.total in Blood by Electrophoresis	4549-2	LOINC	NO	NO	NO
3005673	Hemoglobin A1c/Hemoglobin.total in Blood by HPLC	17856-6	LOINC	NO	NO	NO
40762352	Hemoglobin A1c/Hemoglobin.total in Blood by IFCC protocol	59261-8	LOINC	NO	NO	NO
2212392	Hemoglobin; glycosylated (A1C)	83036	CPT4	NO	NO	NO

B.58 Venous thromboembolism

B.58.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Venous thromboembolism (pulmonary embolism and deep vein thrombosis)’.

B.58.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.58.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 180 days of each other.

B.58.4 Concept: [LEGEND HTN] Venous thromboembolism (pulmonary embolism and deep vein thrombosis)

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
435616	Amniotic fluid embolism	17263003	SNOMED	YES	YES	NO
435887	Antepartum deep vein thrombosis	49956009	SNOMED	YES	YES	NO
196715	Budd-Chiari syndrome	82385007	SNOMED	YES	YES	NO
4062269	Cerebral venous thrombosis in pregnancy	200259003	SNOMED	YES	YES	NO
442055	Obstetric air pulmonary embolism	200286003	SNOMED	YES	YES	NO
433832	Obstetric blood-clot pulmonary embolism	200299000	SNOMED	YES	YES	NO
435026	Obstetric pulmonary embolism	200284000	SNOMED	YES	YES	NO
440477	Obstetric pyemic and septic pulmonary embolism	267284008	SNOMED	YES	YES	NO
318137	Phlebitis and thrombophlebitis of intracranial sinuses	192753009	SNOMED	YES	YES	NO
199837	Portal vein thrombosis	17920008	SNOMED	YES	YES	NO
438820	Postpartum deep phlebothrombosis	56272000	SNOMED	YES	YES	NO
440417	Pulmonary embolism	59282003	SNOMED	NO	YES	NO
254662	Pulmonary infarction	64662007	SNOMED	NO	YES	NO
4235812	Septic thrombophlebitis	439731006	SNOMED	YES	YES	NO
195294	Thrombosed hemorrhoids	75955007	SNOMED	YES	YES	NO
4187790	Thrombosis of retinal vein	46085004	SNOMED	YES	YES	NO
444247	Venous thrombosis	111293003	SNOMED	NO	YES	NO
44834756	Acute venous embolism and thrombosis of other specified veins	453.8	ICD9CM	NO	NO	NO

B.59 Vertigo

B.59.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrence of ‘[LEGEND HTN] Vertigo’ for the first time in the person’s history.

Limit cohort entry events to the earliest event per person.

B.59.2 Cohort Exit

The person also exists the cohort at the end of continuous observation.

B.59.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 0 days of each other.

B.59.4 Concept: [LEGEND HTN] Vertigo

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
437496	Epidemic vertigo	186738001	SNOMED	NO	YES	NO
78162	Peripheral vertigo	50438001	SNOMED	NO	YES	NO
439383	Vertigo	399153001	SNOMED	NO	YES	NO
381035	Vertigo of central origin	38403006	SNOMED	NO	YES	NO

B.60 Vomiting

B.60.1 Cohort Entry Events

People enter the cohort when observing any of the following:

condition occurrences of ‘[LEGEND HTN] Vomiting’.

B.60.2 Cohort Exit

The cohort end date will be offset from index event’s start date plus 1 day.

B.60.3 Cohort Eras

Remaining events will be combined into cohort eras if they are within 30 days of each other.

B.60.4 Concept: [LEGEND HTN] Vomiting

Concept ID	Concept Name	Code	Vocabulary	Excluded	Descendants	Mapped
40480290	Hyperemesis	444673007	SNOMED	YES	YES	NO
4216862	Postoperative vomiting	72245005	SNOMED	YES	YES	NO
441408	Vomiting	422400008	SNOMED	NO	YES	NO
440785	Vomiting of pregnancy	90325002	SNOMED	YES	YES	NO

C Negative Control Concepts

Table C.1: Negative outcome controls specified through condition occurrences that map to (a descendent of) the indicated concept ID
	Concept ID
Abnormal posture	439935
Abnormal pupil	436409
Abrasion and/or friction burn of multiple sites	443585
Abrasion and/or friction burn of trunk without infection	199192
Absence of breast	4088290
Absent kidney	4092879
Acquired hallux valgus	75911
Acquired keratoderma	137951
Anal and rectal polyp	73241
Anomaly of jaw size	45757682
Benign paroxysmal positional vertigo	81878
Bizarre personal appearance	4216219
Burn of forearm	133655
Cachexia	134765
Calcaneal spur	73560
Cannabis abuse	434327
Changes in skin texture	140842
Chondromalacia of patella	81378
Cocaine abuse	432303
Colostomy present	4201390
Complication due to Crohn’s disease	46269889
Complication of gastrostomy	434675
Contact dermatitis	134438
Contusion of knee	78619
Crohn’s disease	201606
Derangement of knee	76786
Developmental delay	436077
Deviated nasal septum	377910
Difficulty sleeping	4115402
Disproportion of reconstructed breast	45757370
Effects of hunger	433111
Endometriosis	433527
Epidermoid cyst	4170770
Exhaustion due to excessive exertion	437448
Feces contents abnormal	4092896
Feces contents abnormal	4092896
Foreign body in ear	374801
Foreign body in orifice	259995
Foreskin deficient	4096540
Galactosemia	439788
Ganglion cyst	40481632
Ganglion cyst	40481632
Genetic disorder carrier	4168318
Hammer toe	433577
Hereditary thrombophilia	4231770
High risk sexual behavior	4012570
Homocystinuria	4012934
Impacted cerumen	374375
Impacted cerumen	374375
Impingement syndrome of shoulder region	4344500
Inadequate sleep hygiene	40481897
Ingrowing nail	139099
Injury of knee	444132
Jellyfish poisoning	4265896
Kwashiorkor	432593
Lagophthalmos	381021
Late effect of contusion	434203
Late effect of motor vehicle accident	438329
Lipid storage disease	4027782
Lymphangioma	433997
Macular drusen	4083487
Malingering	4051630
Marfan’s syndrome	258540
Mechanical complication of internal orthopedic device, implant AND/OR graft	432798
Melena	4103703
Minimal cognitive impairment	439795
Nicotine dependence	4209423
Nicotine dependence	4209423
Noise effects on inner ear	377572
Non-toxic multinodular goiter	136368
Nonspecific tuberculin test reaction	40480893
Nonspecific tuberculin test reaction	40480893
Opioid abuse	438130
Opioid abuse	438130
Opioid intoxication	4299094
Passing flatus	4091513
Physiological development failure	437092
Poisoning by tranquilizer	433951
Postviral fatigue syndrome	4202045
Presbyopia	373478
Psychalgia	439790
Ptotic breast	81634
Regular astigmatism	380706
Senile hyperkeratosis	141932
Social exclusion	4019836
Somatic dysfunction of lumbar region	36713918
Splinter of face without major open wound	443172
Sprain of ankle	81151
Strain of rotator cuff capsule	72748
Symbolic dysfunction	432436
Tear film insufficiency	378427
Tobacco dependence syndrome	437264
Tooth loss	433244
Toxic effect of lead compound	436876
Toxic effect of tobacco and nicotine	440612
Tracheostomy present	4201387
Unsatisfactory tooth restoration	45757285
Verruca vulgaris	140641
Wrist joint pain	4115367
Wristdrop	440193

RESEARCH PROTOCOL Large-scale evidence generation and evaluation across a network of databases for hypertension stepped-care treatment (LEGEND-HtnStepCare)

Version: 0.0.2

1 List of Abbreviations

2 Responsible Parties

2.1 Investigators

2.2 Disclosures

3 Abstract

4 Amendments and Updates

5 Milestones

6 Rationale and Background

7 Study Objectives

8 Research Methods

8.1 Study Design

8.2 Data Sources

8.3 Study Population

8.4 Exposure Comparators

8.4.1 Class-vs-Class Study comparisons

8.4.2 Drug-vs-Drug Study comparisons

8.4.3 Heterogeneity Study comparisons

8.4.4 Validation

8.5 Outcomes

8.6 Analysis

8.6.1 Contemporary utilization of drug classes and individual agents

8.6.2 Relative risk of cardiovascular and patient-centered outcomes

8.6.3 Sensitivity analyses and missingness

9 Sample Size and Study Power

10 Strengths and Limitations

10.1 Strengths

10.2 Limitations

11 Protection of Human Subjects

12 Management and Reporting of Adverse Events and Adverse Reactions

13 Plans for Disseminating and Communicating Study Results

13.1 Transparent and re-usable research tools

13.2 Continuous sharing of results

13.3 Scientific meetings and publications

13.4 General public

References

Appendix

A Exposure Cohort Definitions

A.1 Class-vs-Class Exposure (First ACEI adding Thiazide) Cohort

A.1.1 Cohort Entry Events

A.1.2 Additional Inclusion Criteria

I. rule1

II. rule2

III. rule3

IV. rule4

V. rule5

A.1.3 Cohort Exit

A.1.4 Cohort Eras

A.1.5 Concept: Second agent

A.1.6 Concept: First agent

A.1.7 Concept: Hypertension

A.1.8 Concept: Antihypertensives

A.1.9 Concept: Other agents

A.1.10 Concept: Previous CV events including acute MI, stroke, HF

A.2 Escalation Exit Criteria (On-treatment 2)

A.3 Heterogenity Study Inclusion Criteria

A.3.1 Young age subgroup

A.3.2 Middle age subgroup

A.3.3 Old age subgroup

A.3.4 Female subgroup

A.3.5 Male subgroup

A.3.6 Black or African American subgroup

A.4 Drug-vs-Drug Exposure (First amlodipine adding acebutolol

A.4.1 Cohort Entry Events

A.4.2 Additional Inclusion Criteria

I. rule1

II. rule2

III. rule3

IV. rule4

V. rule5

A.4.3 Cohort Exit

A.4.4 Cohort Eras

A.4.5 Concept: Second agent

A.4.6 Concept: First agent

A.4.7 Concept: Hypertension

A.4.8 Concept: Antihypertensives

A.4.9 Concept: Other agents

A.4.10 Concept: Previous CV events including acute MI, stroke, HF

B Outcome Cohort Definitions

RESEARCH PROTOCOL

Large-scale evidence generation and evaluation across a network of databases for hypertension stepped-care treatment (LEGEND-HtnStepCare)