The impact of sex on the associations between ace inhibitors and cough and angioedema: A systematic review and meta-analysis

Background/Introduction: Cough and angioedema are well-known adverse effects of angiotensin-converting enzyme (ACE) inhibitors. Some observational studies in patients using ACE inhibitors have observed that women have a higher incidence of cough and angioedema than men. Objective/Aim: To evaluate based on randomized controlled trials (RCTs), whether the risks of developing cough and angioedema with ACE inhibitors are modified by sex. Methods: We searched PubMed and Cochrane databases for all years to August 2016. We included RCTs that contain information about the incidence of cough and angioedema in users of ACE inhibitors and controls (active/placebo) in men and women. We performed meta-analyses using the random effects model. Pooled risk ratios (RRs) for cough and angioedema associated with ACE inhibitors in women and men were estimated and tested for interaction. Results: We included four RCTs in our analysis (three studies for cough and two studies for angioedema). We found that there was no difference in the RR to develop cough or angioedema for ACE inhibitors versus controls between women and men. For cough in women, the RR was 3.70; 95%CI (2.55-5.35) and for men, 2.61; 95%CI (1.30-5.27) (P value for interaction 0.39). For angioedema, these RRs were 5.56; 95%CI (2.45-12.62) and 6.35; 95%CI (1.81-22.36), respectively (P value for interaction 0.86). Conclusion: Our meta-analyses show that the risks of developing cough and angioedema associated with ACE inhibitors are not modified by sex. However, these findings should be interpreted cautiously due to limited number of studies involved.