Adverse Effects of Angiotensin-Converting Enzyme Inhibitors in Humans: A Systematic Review and Meta-Analysis of 378 Randomized Controlled Trials

Background: Although angiotensin-converting enzyme (ACE) inhibitors are among the most-prescribed medications in the world, the extent to which they increase the risk of adverse effects remains uncertain. This study aimed to systematically determine the adverse effects of ACE inhibitors versus placebo across a wide range of therapeutic settings. Methods: Systematic searches were conducted on PubMed, Web of Science, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing an ACE inhibitor to a placebo were retrieved. The relative risk (RR) and its 95% confidence interval (95% CI) were utilized as a summary effect measure. A random-effects model was used to calculate pooled-effect estimates. Results: A total of 378 RCTs fulfilled the eligibility criteria, with 257 RCTs included in the meta-analysis. Compared with a placebo, ACE inhibitors were associated with an significantly increased risk of dry cough (RR = 2.66, 95% CI = 2.20 to 3.20, p < 0.001), hypotension (RR = 1.98, 95% CI = 1.66 to 2.35, p < 0.001), dizziness (RR = 1.46, 95% CI = 1.26 to 1.70, p < 0.001), and hyperkalemia (RR = 1.24, 95% CI = 1.01 to 1.52, p = 0.037). The risk difference was quantified to be 0.037, 0.030, 0.017, and 0.009, respectively. Conclusions: We quantified the relative risk of numerous adverse events associated with the use of ACE inhibitors in a variety of demographics. This information can help healthcare providers be fully informed about any potential adverse consequences and make appropriate suggestions for their patients requiring ACE inhibitor therapy.