Eplerenone may also reduce risk of heart failure, shows REMINDER trial

American College of CardiologyMar 13 2013

Results of REMINDER trial show that in addition to standard treatment, eplerenone may also reduce risk of heart failure

The prescription drug eplerenone appears to reduce the risk of cardiovascular mortality and heart failure after a heart attack by more than one-third, according to research presented today at the American College of Cardiology's 62nd Annual Scientific Session.

The REMINDER (Reduction of heart failure morbidity in patients with acute ST-elevation myocardial infarction) trial was a randomized, double-blind trial of 1,012 patients who had a heart attack caused by a complete blockage of one of the heart's arteries. Patients had no signs or history of heart failure. They were given either eplerenone or placebo in addition to standard therapy. Overall, patients taking eplerenone were 38 percent less likely to have poor outcomes than those given a placebo.

Eplerenone counteracts a hormone called aldosterone, which can increase blood pressure. The drug is currently approved to treat hypertension and as a treatment for patients who have heart failure several days after a heart attack.

"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 Gilles Montalescot, MD, PhD, lead investigator of the study and professor of cardiology and head of the Cardiac Care Unit at Piti--Salp-tri-re Hospital, Paris.

About 5.8 million Americans have heart failure, a condition in which the heart cannot pump enough blood to meet the body's oxygen and energy needs. Improvements in heart attack treatment have increased chances of survival, but damage after heart attack is one risk factor for heart failure. Clinical trials and registries show that in the 30 days after a first heart attack, between 8.6 percent and 40 percent of patients will be diagnosed with heart failure.

The primary endpoint of the REMINDER trial included several outcomes:

• Cardiovascular mortality
• Rehospitalization or extended initial hospital stay due to heart failure
• Severe rhythm disruptions of the heart (arrhythmias)
• Ejection fraction of 40 percent or lower after one month, which can indicate heart failure
• An elevation of brain natriuretic peptide (BNP) and its associated protein, NT-proBNP, after one month, which can indicate heart failure

Patients who had one of these outcomes were considered to have reached the primary endpoint. After a mean follow-up of 10.5 months, patients on eplerenone had one of these outcomes less often than those receiving placebo (18.4 vs. 29.6 percent, p<0.0001). Also, only 16 percent of patients on eplerenone had an elevation of BNP/NT-proBNP after one month, compared with 25.9 percent receiving placebo (p<0.0002). Adverse events rates were similar in both groups.

"Eplerenone has the potential to reduce clinical and subclinical heart failure in STEMI patients," Dr. Montalescot said.

The study population was low-risk (the mortality rate was 0.4 percent) 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, Dr. Montalescot added.