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

Author:

Chen RuiJun12ORCID,Suchard Marc A.34ORCID,Krumholz Harlan M.56ORCID,Schuemie Martijn J.37ORCID,Shea Steven8ORCID,Duke Jon9,Pratt Nicole10,Reich Christian G.11ORCID,Madigan David12ORCID,You Seng Chan13,Ryan Patrick B.1,Hripcsak George114ORCID

Affiliation:

1. Department of Biomedical Informatics, Columbia University Irving Medical Center, New York (R.C., P.B.R., G.H.).

2. Department of Translational Data Science and Informatics, Geisinger, Danville, PA (R.C.).

3. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles (M.A.S., M.J.S.).

4. Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (M.A.S.).

5. Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT (H.M.K.).

6. Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, CT (H.M.K.).

7. Epidemiology Analytics, Janssen Research and Development, Titusville, NJ (M.J.S.).

8. Department of Medicine (S.S.), Columbia University, New York.

9. Georgia Tech Research Institute, Georgia Tech College of Computing, Atlanta (J.D.).

10. Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia (N.P.).

11. Real World Solutions, IQVIA, Cambridge, MA (C.G.R.).

12. Department of Statistics (D.M.), Columbia University, New York.

13. Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea (S.C.Y.).

14. Medical Informatics Services, New York-Presbyterian Hospital (G.H.).

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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