FPIN's Help Desk Answers

Pharmacologic Therapy for Heart Failure


Am Fam Physician. 2019 Jul 1;100(1):49-50.

Clinical Question

Should physicians use a combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB) in patients with heart failure?

Evidence-Based Answer

Compared with monotherapy, the combination of an ACE inhibitor and an ARB has not been shown to improve cardiovascular or overall mortality in patients with symptomatic heart failure. The combination is associated with an increased number of adverse drug effects. (Strength of Recommendation [SOR]: A, based on a meta-analysis and randomized controlled trial [RCT].)

Evidence Summary

A 2012 meta-analysis of 24 RCTs evaluated the use of ARBs in patients who had symptomatic heart failure with left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] 40% or less) and preserved ejection fraction (LVEF greater than 40%).1 The meta-analysis included studies comparing ARBs vs. placebo, ARBs vs. ACE inhibitors, or ACE inhibitors plus ARBs vs. ACE inhibitors alone. The dual vs. monotherapy comparison comprised 8,260 patients (20% women) with a mean age of 63 years (range: 60 to 66 years) and a mean LVEF of 27% (range: 20% to 29%). Primary outcomes included total mortality (cardiovascular and noncardiovascular), cardiovascular morbidity (myocardial infarction, stroke), total hospitalizations, and withdrawal due to adverse drug effects. There was no difference in total mortality (seven studies; n = 8,260; relative risk [RR] = 0.98; 95% CI, 0.90 to 1.06) or cardiovascular mortality (two studies; n = 7,558; RR = 0.93; 95% CI, 0.84 to 1.03) between the groups. There was a significant decrease in the number of myocardial infarctions in the combination therapy group (one study; n = 2,548; RR = 0.64; 95% CI, 0.44 to 0.92) and a decrease in the risk of hospitalization for heart failure (two studies; n = 2,989; RR = 0.81; 95% CI, 0.74 to 0.89). Compared with the monotherapy group, the dual therapy group had a significant increase in the number of patients who withdrew because of adverse drug effects

Address correspondence to Scott Christensen, MD, at scott.christensen@fmridaho.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


1. Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev. 2012;(4):CD003040.

2. Kum LC, Yip GW, Lee PW, et al. Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failure. Int J Cardiol. 2008;125(1):16–21.

3. Yancy CW, Jessup M, Boskurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary. Circulation. 2013;128(16):1810–1852.

Help Desk Answers provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (https://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to https://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, Associate Medical Editor.

A collection of FPIN's Help Desk Answers published in AFP is available at https://www.aafp.org/afp/hda.



Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP

Editor's Collections

Related Content

More in Pubmed


Apr 1, 2020

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article