Effects of Mineralocorticoid Receptor Antagonists on Atrial Fibrillation Occurrence: A Systematic Review, Meta-Analysis, and Meta-Regression to Identify Modifying Factors

Background Mineralocorticoid receptor antagonists (MRAs) have emerged as potential atrial fibrillation (AF) preventive therapy, but inconsistent results have been reported. We aimed to examine the effects of MRAs on AF occurrence and explore factors that could influence the magnitude of the effect size. Methods and Results PubMed, Embase, and Cochrane Central databases were used to search for randomized clinical trials and observational studies addressing the effect of MRAs on AF occurrence from database inception through April 03, 2018. We performed a systematic review and random effects meta-analyses to compute odds ratios with 95% CIs. Meta-regression was then applied to explore the sources of between-study heterogeneity. We included 24 studies, 11 randomized clinical trials and 13 observational cohorts, representing a total number of 7914 patients (median age: 64.2 years; median left ventricular ejection fraction: 49.7%; median follow-up: 12.0 months), 2843 (35.9%) of whom received MRA therapy. Meta-analyses showed a significant overall reduction in AF occurrence in the MRA-treated patients versus the control groups (15.0% versus 32.2%; odds ratio, 0.55; 95% CI, 0.44-0.70 [P<0.00001]), with the greatest benefit regarding recurrent AF episodes (odds ratio, 0.42; 95% CI, 0.31-0.59 [P<0.00001]) and with significant heterogeneity among the included studies (I²=54%; P=0.0008). Meta-regression analyses showed that effect size was significantly associated with older studies and higher AF occurrence rate in the control groups. Conclusions MRAs seem to be effective in AF prevention, especially regarding recurrent AF episodes.