Eplerenone + Standard of Care Improves Outcomes in Patients with STEMI
SAN FRANCISCO, CA—Adding eplerenone to standard therapy within 24 hours of symptom onset improved outcomes in patients presenting with acute ST-elevation myocardial infarction (STEMI) who had no evidence of heart failure (HF) or left ventricular ejection fraction (LVEF) <40%, results of the REMINDER trial presented at ACC.13, the American College of Cardiology's 62nd Annual Scientific Session, has found.
REMINDER (Reduction of heart failure morbidity in patients with acute ST-elevation myocardial infarction) is “the first randomized trial to test a mineralocorticoid receptor antagonist during the acute phase of heart attack and is the first large study to demonstrate the safety profile of eplerenone during early administration,” said lead study investigator Gilles Montalescot, MD, PhD, professor of cardiology and head of the Cardiac Care Unit at Pitié-Salpétrière Hospital, Paris, France.
The trial randomized 1,012 patients with acute STEMI without a history of HF or LVEF <40% and without signs of HF to receive, “preferably before myocardial reperfusion,” eplerenone (titrated from 25mg/day to 50mg/day on Day 2; n=502) or placebo (n=506). Both groups also received standard of care.
“Eligible subjects were identified for inclusion following emergency room or ambulance evaluation and diagnosis of acute STEMI in the absence of a diagnosis of HF,” Dr. Montalescot said. “Randomization had to take place as early as possible following diagnosis and the first dose of study drug administered as early as possible within 24 hours of the onset of symptoms of acute MI and preferably within 12 hours.”
The primary composite end point was time to first event of CV mortality, re-hospitalization, or extended initial hospital stay due to diagnosis of HF or sustained ventricular tachycardia or fibrillation, LVEF ≤40% 1 month post-randomization, or an elevation of brain natriuretic peptide (BNP) and its associated protein, NT-proBNP, after 1 month.
“After a mean follow-up of 10.5 months, the primary composite end point occurred in 93 (18.4%) of patients in the eplerenone group as compared with 150 (29.6%) in the placebo group (adjusted hazard ratio [HR], 0.581 [0.449–0.753]; P<0.0001,” he reported.
Elevated BNP/T-proBNP after 1 month was observed in 81 (16%) of patients in the eplerenone group compared with 131 (25.9%) in the placebo group (adjusted HR, 0.584; [0.441–0.773]; P<0.0002). Adverse events rates were similar in both groups. Serum potassium levels exceeding 5.5mEq/L occurred in 5.6% vs. 3.2% (P=0.09) and potassium levels below 4.0mEq/L occurred in 35.5 vs. 47.2% (P=0.0002) in the eplerenone and placebo groups, respectively.
The study population was low-risk (mortality rate was 0.4%) and was receiving standard treatment. “Despite this, a benefit was observed with eplerenone to prevent adverse outcomes and subclinical heart failure,” Dr. Montalescot said. “Confirmation in a higher-risk population with a longer follow-up would be important to support this new strategy.”The ongoing ALBATROSS (Aldosterone Blockade Early After Acute Myocardial Infarction) study is investigating this hypothesis, he added.