Abstract 18: Aldosterone Antagonists Prevent Sudden Cardiac Death in patients with Left Ventricular Systolic Dysfunction: a Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Sudden Cardiac Death (SCD) is a leading cause of mortality in patients with left ventricular systolic dysfunction (LVSD). The renin-angiotensin-aldosterone pathway has been implicated in the pathogenesis of SCD. A meta-analysis of randomized controlled trials (RCTs) to assess the impact of aldosterone antagonists (AA) on SCD in patients with LVSD has been lacking. Methods: We systematically searched PubMed, EMBASE, Cochrane, US Food and Drug Administration and Clinical Trials databases through March 31, 2011 without language restrictions. We included trials that enrolled patients with LVSD (LV ejection fraction ≤ 45%), randomized subjects to an AA vs. placebo, and reported outcomes of SCD. Pooled odds ratios were calculated using DerSimonian and Laird random effects model. Heterogeneity was measured by Cochran’s Q test and I 2 statistic. Sensitivity analysis was performed to evaluate the strength of our model. Publication bias was explored with a funnel plot and Eggers test. A two sided p-value of < 0.05 was considered statistically significant. Results: We identified six published trials, which enrolled 11,654 patients, and met inclusion criteria (Table 1). No significant heterogeneity was observed among the trials. Patients with LVSD treated with AA had 23% lower odds of experiencing SCD compared with controls. Similar results were observed with secondary outcomes of total and cardiovascular mortality. Sensitivity analysis did not significantly change the odds ratio. Significant publication bias was observed (asymmetrical funnel plot and Eggers test p = 0.01) due to the inclusion of small trials with less precision and large trials with high effect size in the final synthesis. We found a trivial shift in the effect size from 0.770 to 0.776 after a trim and fill test to account for hypothetically missed studies suggesting that the impact of the publication bias on these findings is probably insignificant. Conclusions: AA reduce the risk of SCD in patients with LVSD. Comparative effectiveness studies of AA on SCD in the usual care setting as well as other SCD-prevention strategies in the setting of AA use are needed.