MRAs reduce SCD risk in some patients

Mineralocorticoid receptor antagonists (MRAs) reduce the risk of sudden cardiac death (SCD) in patients with left ventricular systolic dysfunction (LVSD), according to a meta-analysis. The study was published online Feb. 12 in Circulation: Heart Failure.

Patients with LVSD are at high risk of SCD from arrhythmias, and implantation of implantable cardioverter-defibrillators may improve survival. But while American College of Cardiology (ACC), American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines recommend ICDs as a primary prevention for SCD in these patients, the use in hospitals is variable, ranging from a rate of 1 to 35 percent (J Am Coll Cardiol 2009;3;53[5]:416-22).

Srinivas R. Bapoje, MD, MPH, of the cardiology department at the University of Arkansas for Medical Sciences in Little Rock, and colleagues hypothesized that MRAs such as spironolactone and eplerenone might serve as an adjunctive therapy for LVSD patients. To test their theory, they performed a meta-analysis based on clinical trials of MRAs used in the LVSD setting.

They searched PubMed (MEDLINE), EMBASE, Cochrane, FDA and clinical trials databases and abstracts from ACC and AHA conferences through March 30, 2012, to identify trials that enrolled adult patients with symptomatic or asymptomatic heart failure and left ventricular ejection fraction of 45 percent or less who had been assigned to either MRAs, placebo or control.

To be considered, the trials had to include 25 patients or more in both groups and to have a duration and follow-up period of two months or more. They used the ACC/AHA/ESC guideline definition of SCD. The primary outcome was SCD and the secondary outcomes were total and cardiovascular mortality.

They found eight published studies that included 11,875 patients, half of whom came from the EPHESUS trial. Of the total patient group, 6 percent experienced SCD; within the SCD group, 2.6 percent were treated with MRAs. They calculated that patients with LVSD who were treated with MRAs had 23 percent lower odds of SCD compared the placebo/control group. They found similar reductions in total and cardiovascular mortality.

“The substantial reduction in the risk of SCD with MRAs therapy in patients with LVSD identified in this study has important implications,” Bapoje et al wrote. “First, few of the patients enrolled in the trials of MRA for systolic heart failure were treated with ICDs, providing the ability to ascertain the independent benefits of MRA on this important outcome. Second, the effect of MRAs on SCD is important given the fact that MRAs are a particularly underutilized class of medications in patients with heart failure and have a high potential impact on reduction of mortality among evidence-based therapies for heart failure with optimal implementation.”

The researchers added that the benefits of eplerenone were similar to spironolactone, but that the former has fewer side effects. Also, an analysis of subgroups found MRAs benefited patients with milder LVSD who might not be considered as candidates for ICDs.

They recommended that further research be conducted to evaluate the effectiveness and cost-effectiveness of ICD use in patients treated with medical therapy, including MRAs, and encouraged physicians to treat LVSD patients who refuse ICDs with MRAs.  

They acknowledged that their meta-analysis might have missed unpublished randomized trials; the trials in the meta-analysis used differing definitions of SCD but that subgroup analyses did not detect differences in effect sizes; and publication bias could have influenced the results.