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ACE inhibitors tied to increased angioedema risk

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Pooled data suggest that use of renin–angiotensin system (RAS) inhibitors, particularly angiotensin converting enzyme (ACE) inhibitors may increase the risk of angioedema, researchers report in an April 20th on-line paper in the American Journal of Cardiology.

Nevertheless, Dr. Franz H. Messerli told Reuters Health by email, “ACE inhibitors are among the most efficacious and safest drugs available to the practicing physician and are extensively used all over the globe. However despite this widespread use, angioedema remains a rare, but potentially fatal adverse event of this drug class.”

To assess this risk, Dr. Messerli of Columbia University College of Physicians and Surgeons, New York and colleagues examined data on 26 trials of ACE inhibitors, 19 of angiotensin receptor blockers (ARBs), and 2 with a direct renin inhibitor (DRI). Numbers were greater than 74,000 in the ACE arm, 35,000 in the ARB arm and 5000 in the DRI group.

In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs. With both such agents the incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure.

Of the patients on ACE inhibitors, 394 developed angioedema during a mean duration of 129 weeks giving a weighted incidence of 0.30%. For ARBs, 52 developed angioedema during a mean duration of 120 weeks (0.11%). Of those given a DRI, 7 developed angioedema during a mean duration of 24 weeks (0.13%). The incidence with placebo was 0.07%.

Thus overall, the incidence of angioedema with ARBs and DRI was not significantly different from placebo and less than half that with ACE inhibitors.

In two of trials examined, Dr. Messerli added, “there was a death associated with ACE inhibitor related angioedema. This together with our study clearly illustrate that physicians need to remain vigilant regarding this entity and continue to quiz all patients on ACE inhibitors regarding unexpected swelling of lips, throat and larynx.”

In addition, the team found that African-Americans were twice as likely to develop angioedema on ACE inhibitors compared to Caucasians.

Dr. Messerli concluded that although definitive data are lacking, “Since African Americans have a risk of angioedema that is substantially higher than in Caucasians, ARBs probably should be preferred over ACE inhibitors in this patient group.”


Meta-Analysis of Randomized Trials of Angioedema as an Adverse Event of Renin–Angiotensin System Inhibitors

Am J Cardiol 2012.