Similar effectiveness of ACEi and ARB as hypertension treatment in real-world

Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers.

Literature - Chen RJ, Suchard MA, Krumholz HM, et al. - Hypertension. 2021, DOI: 10.1161/HYPERTENSIONAHA.120.16667

Introduction and methods

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are equally recommended as first-line therapy for the treatment of hypertension in the 2017 ACC/AHA and 2018 ESC/ESH guidelines. However, there are limited head-to-head studies comparing the effectiveness and safety of ACEi with ARBs as hypertension monotherapy and the few available studies have shown conflicting results [1-3]. Though, ACEi are far more commonly prescribed worldwide for the treatment of hypertension [4-7].

This long-term observational study compared the effectiveness and safety of ACEi or ARB therapy for first-line treatment of patients with hypertension in a real-world setting.

This study used 7 observational databases in the open-science LEGEND-HTN (Large-scale Evidence Generation and Evaluation across a Network of Database for Hypertension). All patients initiating antihypertensive treatment with a single drug (ACEi [n= n=2,297,881] or ARB [n=673,938]) were included. Data from July 1996 to March 2018 were used. Propensity score models were used to adjust for potential confounding and to improve balance between the ACEi and ARB patients cohorts. Also, calibration was applied to account for residual bias using negative control outcomes. The primary effectiveness outcomes were acute MI, HF hospitalization, stroke, and a composite CV events (CVEs) outcome consisting of MI, HF hospitalization, stroke, and sudden cardiac death. Secondary safety outcomes included angioedema, cough, hypotension, syncope, and electrolyte abnormalities.

Main results

  • 48% of patients initiated monotherapy with an ACEi, while 15% of patients initiated treatment with an ARB.
  • There were no differences between patients on ACEi vs. ARBs for the primary effectiveness outcome of acute MI (HR 1.11, 95% CI: 0.95-1.32), HF hospitalization (HR 1.03, 95% CI: 0.87-1.24), stroke (HR 1.07, 95% CI: 0.91-1.27) or CVEs (HR 1.06, 95% CI:0.90-1.25).
  • Patients receiving ACEi had a significant elevated risk for acute pancreatitis (HR 1.32, 95% CI: 1.04-1.70, P=0.02), angioedema (HR 3.31, 95% CI: 2.55-4.51, P<0.01), cough (HR 1.32, 95% CI: 1.11-1.59, P<0.01), gastrointestinal bleed (HR 1.18, 95% CI: 1.01-1.41, P=0.04), and abnormal weight loss (HR 1.18, 95% CI: 1.01-1.41, P=0.04) as well as decreased risk of abnormal weight gain (HR 0.84, 95% CI: 0.74-0.98, P=0.04) compared to those treated with an ARB. Using a conservative Bonferronni correction, cough and angioedema remained significant.


This large observational study including over 3 million patients worldwide showed that the effectiveness of ACEi vs. ARB treatment as first-line therapy for the treatment of hypertension on CV outcomes was comparable. Cough and angioedema were increased in patients receiving ACEi compared to patients initiating ARB.


1. Li EC, heran BS, and Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2014;2014:CD009096.

2. Bremner AD, Baur M, oddou-Stock P, and Bodin F. Valsartan: long-term efficacy and tolerability compared to lisinopril in elderly patients with essential hypertension. Clin Exp Hypertens. 1997;19:1263-85.

3. Spinar J, Vítovec J, Souček M, et al., CORD investigators. CORD: COmparison of Recommended Doses of ace inhibitors and angiotensin II receptor blockers Int J Cardiol. 2010;144:293-294.

4. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-e115.

5. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur. Heart J. 2018;39:3021-3104

6. Hripcsak G, Ryan PB, Duke JD, et al. Characterizing treatment pathways at scale using the OHDSI network. Proc Natl Acad Sci U S A. 2016;113:7329-36.

7. Gu Q, Burt VL, Dillon CF, and Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health And Nutrition Examination Survey, 2001 to 2010. Circulation. 2012;126:2105-2114.

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