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Cited by 190Blood Pressure and Hypertension StudiesRenin-Angiotensin System StudiesCoagulation, Bradykinin, Polyphosphates, and Angioedema

Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study

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Chen, RuiJun, Suchard, Marc A., Krumholz, Harlan M., Schuemie, Martijn J., Shea, Steven, Duke, Jon, Pratt, Nicole, Reich, Christian G. +4 more·2021·Hypertension
DOI 10.1161/hypertensionaha.120.16667PMC PMC8363588
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Abstract

ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) are equally guideline-recommended first-line treatments for hypertension, yet few head-to-head studies exist. We compared the real-world effectiveness and safety of ACE inhibitors versus ARBs in the first-line treatment of hypertension. We implemented a retrospective, new-user comparative cohort design to estimate hazard ratios using techniques to minimize residual confounding and bias, specifically large-scale propensity score adjustment, empirical calibration, and full transparency. We included all patients with hypertension initiating monotherapy with an ACE inhibitor or ARB between 1996 and 2018 across 8 databases from the United States, Germany, and South Korea. The primary outcomes were acute myocardial infarction, heart failure, stroke, and composite cardiovascular events. We also studied 51 secondary and safety outcomes including angioedema, cough, syncope, and electrolyte abnormalities. Across 8 databases, we identified 2 297 881 patients initiating treatment with ACE inhibitors and 673 938 patients with ARBs. We found no statistically significant difference in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11 for ACE versus ARB [95% CI, 0.95–1.32]), heart failure (hazard ratio, 1.03 [0.87–1.24]), stroke (hazard ratio, 1.07 [0.91–1.27]), or composite cardiovascular events (hazard ratio, 1.06 [0.90–1.25]). Across secondary and safety outcomes, patients on ARBs had significantly lower risk of angioedema, cough, pancreatitis, and GI bleeding. In our large-scale, observational network study, ARBs do not differ statistically significantly in effectiveness at the class level compared with ACE inhibitors as first-line treatment for hypertension but present a better safety profile. These findings support preferentially prescribing ARBs over ACE inhibitors when initiating treatment for hypertension.

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References 49 · Cited by 190

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Authors
Chen, R., Suchard, M. A., Krumholz, H. M., Schuemie, M. J., Shea, S., Duke, J., Pratt, N., Reich, C. G., Madigan, D., You, S. C., Ryan, P. B., & Hripcsak, G.
Affiliations
  • Columbia University Irving Medical Center (US)
  • University of California, Los Angeles (US)
  • Yale New Haven Hospital (US)
  • Columbia University (US)
  • Georgia Institute of Technology (US)
  • University of South Australia (AU)
  • Real World Solutions, IQVIA, Cambridge, MA (C.G.R.).
  • Ajou University (KR)
  • NewYork–Presbyterian Hospital (US)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-09
Volume
78
Issue
3
Pages
591-603
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.120.16667
PMC
PMC8363588
OpenAlex
W3184024116
Cited by
190
References
49
Citations by year
2026: 36 · 2025: 40 · 2024: 43 · 2023: 44 · 2022: 23 · 2021: 4
FWCI
19.11
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR001863)
  • National Institute of Allergy and Infectious Diseases (U19AI135995)
  • U.S. National Library of Medicine (R01LM006910, T15LM007079)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Keywords
ACE inhibitors, angiotensin receptor blockers, first-line antihypertensive therapy, drug effectiveness, drug safety, acute myocardial infarction, heart failure, stroke, cardiovascular events, angioedema, cough, pancreatitis, gastrointestinal bleeding, comparative effectiveness
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Child, Child, Preschool, Female, Humans, Hypertension, Infant, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Young Adult, Angiotensin Receptor Antagonists

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