Effects of Mineralocorticoid Receptor Antagonists on the Risk of Sudden Cardiac Death in Patients With Left Ventricular Systolic Dysfunction

BACKGROUND: Sudden cardiac death (SCD) is an important cause of death in patients with left ventricular systolic dysfunction. Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. The objective of this meta-analysis was to assess the impact of MRAs on SCD in patients with left ventricular systolic dysfunction. METHODS AND RESULTS: We systematically searched PubMed, EMBASE, Cochrane, and other databases through March 30, 2012, without language restrictions. We included trials that enrolled patients with left ventricular ejection fraction of ≤45%, randomized subjects to MRAs versus control and reported outcomes on SCD, total and cardiovascular mortality. Eight published trials that enrolled 11 875 patients met inclusion criteria. Of these, 6 reported data on SCD and cardiovascular mortality, and 7 reported data on total mortality. No heterogeneity was observed among the trials. Patients treated with MRAs had 23% lower odds of experiencing SCD compared with controls (odds ratio, 0.77; 95% confidence interval, 0.66-0.89; P=0.001). Similar reductions were observed in cardiovascular (0.75; 95% confidence interval, 0.68-0.84; P<0.001) and total mortality (odds ratio, 0.74; 95% confidence interval, 0.63-0.86; P<0.001). Although publication bias was observed, the results did not change after a trim and fill test, suggesting that the impact of this bias was likely insignificant. CONCLUSIONS: MRAs reduce the risk of SCD in patients with left ventricular systolic dysfunction. Comparative effectiveness studies of MRAs on SCD in usual care as well as studies evaluating the efficacy of other therapies to prevent SCD in patients receiving optimal MRA therapy are needed to guide clinical decision-making.