SAN FRANCISCO—Adding eplerenone to standard treatment may reduce the risk of cardiovascular mortality and heart failure after MI, according to results of a late-breaking clinical trial presented March 10 at the American College of Cardiology (ACC) scientific session. The treatment could be a potential game-changer if results are sustained, according to panelists.
Gilles Montalescot, MD, PhD, professor of cardiology and head of the cardiac care unit at Pitié-Salpétrière Hospital in Paris, and colleagues enrolled 1,012 patients presenting to the emergency room with acute STEMI and no evidence of heart failure in the REMINDER (Reduction of Heart Failure Morbidity in Patients with Acute STEMI) trial.
Clinical trial and registry data show between 8.6 percent and 40 percent of patients will be diagnosed with heart failure within 30 days of an MI.
Elevated aldosterone at STEMI admission has deleterious effects, such as sodium retention and endothelial dysfunction, Montalescot pointed out. Aldosterone also can increase blood pressure. Eplerenone counteracts aldosterone, and is currently approved to treat hypertension. Eplerenone also is approved and recommended in Europe and the U.S. in patients with heart failure; however, it is hardly ever used in practice.
In the randomized, double-blind trial, patients were randomized as early as possible after diagnosis and by 24 hours.
Patients were excluded on the basis of several criteria: a known ejection fraction of less than 40 percent or any history of heart failure, implanted cardioverter-defibrillator, known renal insufficiency, uncontrolled hypotension and any other clinically significant coexisting condition.
The composite primary endpoint was time to first occurrence of cardiovascular mortality, re-hospitalization or extended initial hospital stay due to diagnosis of heart failure or sustained ventricular tachycardia or ventricular fibrillation and at one-month post-randomization, an ejection fraction of 40 percent or lower and an elevation of brain natriuretic peptide (BNP) and its associated protein (NT-proBNP) after one month.
A total of 506 patients were enrolled in the eplerenone arm and 506 were randomized to the placebo arm. Both groups also received standard therapy.
After a mean follow-up of 10.5 months, patients on eplerenone had any of the outcomes less often than those receiving placebo (18.4 vs. 9.6 percent). Overall, patients taking eplerenone were 38 percent less likely to have poor outcomes than those given a placebo.
A total of 16 percent of patients on eplerenone had an elevation of BNP/NT or proBNP after one month, compared with 25.9 percent receiving placebo. Adverse events rates were similar in both groups.
“This is the first randomized trial to test a mineralocorticoid receptor agonist during the acute phase of heart attack, and the results suggest a clinical benefit,” said Montalescot.
Panelist Miguel A. Quinones, MD, of Methodist DeBakey Cardiology Associates in Houston, noted that the trial had accomplished a difficult task. The study population was low-risk (the mortality rate was 0.4 percent) and was receiving standard treatment, which makes it very difficult to demonstrate benefits.
“Despite this, a benefit was observed with eplerenone to prevent adverse outcomes and subclinical heart failure,” Montalescot said.
The regimen has the potential to be a “game-changer” if results can be demonstrated with three-to-five year data, said Quinones.
“Confirmation in a higher-risk population with a longer follow-up would be important to support this new strategy,” added Montalescot. The ongoing ALBATROSS [Aldosterone Blockade Early After Acute MI] study is investigating this hypothesis.
Finally, REMINDER indicated that short-term use of eplerenone seems to be safe when patients with renal failure are excluded, according to Quinones.