Benefits and adverse effects of ACE inhibitors in patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

Eur J Clin Pharmacol. 2021 Mar;77(3):321-329. doi: 10.1007/s00228-020-03018-4. Epub 2020 Oct 17.

Abstract

Purpose: Angiotensin-converting enzyme (ACE) inhibitors are part of first-line treatment for reduced ejection fraction heart failure (HFrEF). The aim was to assess the benefits and adverse effects of ACE inhibitors in HFrEF with a focus on important patient outcomes.

Methods: A systematic review of double-blind randomized clinical trials (RCTs) and comparison of ACE inhibitors versus placebo, in HFrEF patients published in French or English. Searches were undertaken of Medline, Cochrane Central, and Embase. The primary outcomes were all-cause mortality and adverse events.

Results: From 636 articles analysed, 11 were included (13,882 patients). For all-cause mortality (5 RCTs, 9277 patients), the number needed to treat (NNT) to avoid one death at 6 months was 50 (33-107). The NNT to prevent one death at 12 months (6 RCTs, 13,016 patients) was 63 (35-314). Under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the evidence was of moderate quality. The number needed to harm was 12 (10-15) for cough, 20 (14-31) for hypotension, 23 (17-36) for dizziness, 31 (23-47) for hyperkalaemia, and 49 (30-121) for increased creatinine levels. The quality of evidence was moderate for these criteria except for cough (low quality of evidence).

Conclusion: This review focuses on clinical elements necessary in a shared decision-making process. In practice, general practitioners will be able to use these data to discuss ACE inhibitor treatment with HFrEF patients. This study was registered in the PROSPERO registry under the reference number CRD42018096930.

Keywords: ACE inhibitors; General practice; Randomized controlled trials; Shared decision making; Systematic review; Systolic heart failure.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Decision Making, Shared
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Randomized Controlled Trials as Topic
  • Stroke Volume / physiology*

Substances

  • Angiotensin-Converting Enzyme Inhibitors