Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: A meta-analysis

Background: Patients who have angioedema after taking angiotensin- converting enzyme inhibitors (ACE-Is) have been reported to develop angioedema when taking an angiotensin receptor blocker (ARB), but few studies quantify the risk. Objective: To perform a systematic review of the literature. Methods: A literature search was performed in MEDLINE, EMBASE, BIOSIS, and Current Contents, with no limitations from January 1990 to May 2007. Any article that described a cohort of patients who had angioedema after taking an ACE-I, were subsequently exposed to an ARB, and were followed for a least 1 month were included. The percentage of patients who had angioedema was abstracted from each article, and confidence intervals were calculated using the exact binomial method. The pooled percentage was calculated with the inverse variance method. Results: Two-hundred fifty-four unique articles were identified, and 3 articles met inclusion criteria, which described 71 patients with the outcome of interest. One was a randomized controlled trial and 2 were retrospective cohorts. These articles described both confirmed and possible cases of angioedema. The risk of angioedema was 9.4% (95% confidence interval, 1.6%-17%) for possible cases and 3.5% (95% confidence interval, 0.0%-9.2%) for confirmed cases. No fatal events were reported. No statistical heterogeneity was reported between trials (P > .3). Conclusions: Limited evidence suggests that for patients who develop angioedema when taking an ACE-I, the risk of development of any subsequent angioedema when taking an ARB is between 2% and 17%; for confirmed angioedema, the risk is 0% to 9.2%. This information will aid clinicians in counseling patients regarding therapy options after development of angioedema due to ACE-Is.