Abstract 13950: Angioedema as an Adverse Event of Renin-Angiotensin-System Inhibitors - A Meta-Analysis of Randomized Trials
Background: Angioedema is a rare, potentially life threatening adverse event of renin angiotensin system (RAS) inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials.
Methods: A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to present in patients on Angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) or a direct renin inhibitor (DRI). Trials with total number of patients more than 100 and duration of at least 8 weeks were included for analysis. The incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance.
Results: 23 trials with 73,670 patients on ACE inhibitor arm with 230,145 person-years of follow up, 14 trials with 30,710 patients on ARB with 105,671 person-years of follow up and one trial with 4203 patients on DRI and 1157 person-years of follow up met the inclusion criteria and were included in the analysis. The weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI, 0.28-0.32) compared to 0.14% (95% CI, 0.12-0.17) with ARBs, 0.14% (95% CI, 0.08-0.20) with DRIs, 0.10% with placebo, 0.05% with thiazides and 0.03% with calcium channel blockers. In head-to-head comparison in 7 trials, the risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% CI, 1.5 - 3.3). With both ACE inhibitors and ARBs, the incidence of angioedema was higher in heart failure trials compared with hypertension or coronary artery disease trials without heart failure (p<0.0001).
Conclusion: The incidence of angioedema with ARBs and DRI is less than half than that with ACE inhibitors. However, both ARBs and DRI still confer a significantly higher risk of angioedema than placebo, diuretics or CCBs. The incidence of angioedema was higher in patients with heart failure compared to non-heart failure patients with both ACE inhibitors and ARBs.
- © 2011 by American Heart Association, Inc.