Eplerenone in STEMI Patients with No History of Heart Failure

San Francisco—After a mean follow-up of 10.5 months, patients with acute ST-segment elevation myocardial infarction (STEMI) who, having no diagnosis of heart failure, took eplerenone in addition to standard treatment had a significant reduction in the composite end point compared with a group receiving placebo, according to a randomized, double-blind trial.

The composite end point consisted of the time to first occurrence of cardiovascular mortality, rehospitalization or extended initial hospital stay due to diagnosis of heart failure or sustained ventricular tachycardia or ventricular fibrillation. It also included left ventricular ejection fraction ≤40% or elevated blood pressure 1 month after randomization.

Gilles Montalescot, MD, the study’s lead author, presented the data in a late-breaking clinical trial session at the ACC meeting. Pfizer Inc., the drug’s manufacturer, funded the study.

Dr. Montalescot noted that the significant reduction (18.4% of eplerenone patients vs 29.6% of placebo patients; hazard ratio [HR], 0.581; 95% confidence interval [CI], 0.449-0.753; P<.0001) was mostly driven by the reduction in subclinical outcomes evaluated ³1 month after randomization. There was no difference in cardiovascular mortality or rehospitalization. However, there was a significant reduction in the composite of cardiovascular mortality, heart failure episode, or severe ventricular arrhythmia (P=.09).

This trial, called REMINDER (Reduction of Heart Failure Morbidity in Patients with Acute ST-Elevation Myocardial Infarction), only included low-risk patients. The ongoing ALBATROSS [Aldosterone Blockade Early After Acute Myocardial Infarction] study is examining the effectiveness of eplerenone in a higher risk population and has a longer follow-up period.

Previous trials demonstrated eplerenone’s effectiveness. The randomized, double-blind EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) study found that eplerenone significantly reduced mortality in patients with left ventricular systolic dysfunction and mild symptoms of heart failure compared with placebo (24% risk reduction [RR]; P=.0081).

In addition, the EPHESUS (Eplerenone Postacute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial found that patients with left ventricular systolic dysfunction who, after having a recent myocardial infarction, took eplerenone had a significant reduction in mortality compared with those receiving placebo (15% RR; P=.008).

In this study, patients were randomized shortly after being diagnosed with STEMI in the ambulance or emergency department. They received the study drug within 12 to 24 hours of the onset of symptoms of acute MI. Exclusion criteria included patients with any previous history of heart failure, an implanted cardioverter defibrillator, and uncontrolled hypotension.

The authors randomized 1112 patients in a 1:1 ratio to receive 25 mg of eplerenone or placebo at admission to the hospital or in the ambulance. After 24 hours, they were titrated, and most patients (89%) received 50 mg of eplerenone.

The groups were well balanced. The mean age was approximately 58 years, and Dr. Montalescot noted they were “extremely well treated,” with >98% receiving aspirin and P2Y12 antagonists, 98% receiving statins, and 88% receiving beta blockers.

Dr. Montalescot said the authors had safety concerns when designing the study because they administered the drugs without checking for creatinine or potassium levels. However, there were no differences in the groups when comparing adverse events (59.0% in the eplerenone group vs 58.6% in the placebo group; P=.95) or death rates (0.6% in each group; P=1.00). Dr. Montalescot added that this is the first large study to demonstrate eplerenone’s safety profile when administered early in these patients.