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Aldosterone Blocker May Lower Risk of Death, Heart Failure After Heart Attack: Presented at ACC

By Bruce K. Dixon

CHICAGO, IL -- April 3, 2003 -- The addition of aldosterone (eplerenone) to conventional treatment after acute myocardial infarction results in additional reductions in overall mortality and the rate of death from cardiovascular causes among patients whose heart attack was complicated by left ventricular dysfunction and heart failure.

The randomized, controlled EPHESUS study included 6,632 patients in 37 countries. Results were presented here March 31^st at the 52^nd Annual Scientific Session of the American College of Cardiology.

"ACE inhibition and beta blockade is the therapy of choice in patients with systolic left ventricular dysfunction post-infarction and heart failure, but mortality and morbidity in these patients remain relatively high," said Bertram Pitt, MD, with the University of Michigan in Ann Arbor. "Aldosterone blockade has been shown to reduce morbidity and mortality in patients with severe chronic heart failure due to systolic left ventricular dysfunction treated with an ACE inhibitor"

In this study, half the patients (mean age, 64 years) were initially randomized to aldosterone 25 mg daily, titrated to a maximum of 50 mg daily. Remaining patients were assigned to placebo in addition to optimal current medical therapy. The study continued until 1,012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia.

During a mean follow-up of 16 months, there were 478 deaths in the aldosterone group and 554 deaths in the placebo group. Of these deaths, 407 in the drug group and 483 in the placebo group were attributed to cardiovascular causes.

"Aldosterone at a mean dose of 43 mg once daily reduced all-cause mortality by 15%, cardiovascular hospitalizations by 13%, cardiovascular mortality by 17%, sudden cardiac death by 21%, total mortality and total hospitalizations by 8%, patients hospitalized for heart failure by 15%, and episodes of hospitalization for heart failure by 23%," Dr. Pitt told the meeting, adding that these results were relatively consistent across all predefined subsets. The 1-year mortality rate in the placebo group, most of whom received an ACE inhibitor or angiotensin receptor blocker and a beta blocker, was 13.6%.

"The most frequent cause of cardiovascular mortality in this trial was sudden cardiac death," said Dr. Pitt. "When we retrospectively cut our data to look at those with an ejection fraction of less than or equal to.30, there was a significant 33% reduction in sudden cardiac death. Although defibrillators may be effective in this subset of patients, I doubt they would be cost-effective with this level of mortality reduction."

Treatment with aldosterone was safe and well tolerated, having caused no significant increase in impotence or menstrual changes. "There was a 1.6% absolute increase in serious hyperkalemia and a 4.7% absolute decrease in hypokalemia," he said. "Also, there was one life saved per year for every 50 patients treated, and one episode of cardiovascular mortality prevented for every 33 patients treated."

Dr. Pitt concluded that "these results confirm the effectiveness of eplerenone blockade in patients with systolic left ventricular dysfunction, and they have important implications, not only for patients with acute myocardial infarction and heart failure, but for a variety of cardiovascular diseases currently treated with an ACE inhibitor and a beta blocker."

The EPHESUS results, funded by a grant from Pharmacia, appear in the April 3 issue of The New England Journal of Medicine.


[Study title: EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study): A Double-Blind, Randomized, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Eplerenone in Patients With Heart Failure Following Acute Myocardial Infarction. Abstract: 405-3]

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