Eplerenone Reduces All-Cause Mortality After AMI in LVD Patients
March 31, 2003 (Chicago) — Eplerenone, a selective aldosterone blocker, significantly reduces morbidity and mortality when given on top of optimal medical therapy to patients who have left ventricular dysfunction after acute myocardial infarction (AMI), according to results released here at the 52nd annual scientific session of the American College of Cardiology.
The study, Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), will also be published in the April 3 issue of the New England Journal of Medicine and was released early by the journal to coincide with the presentation here.
"This is very satisfying," said Bertram Pitt, MD, professor of medicine at the University of Michigan in Ann Arbor. "This study shows that on top of what we can do today for patients, we can still do better. This represents a new advance in to the treatment of heart attack and heart failure."
He added that patients who received the most aggressive treatment for their heart failure received the greatest benefit from eplerenone therapy.
"I wrote down home run when I heard the results," Jon Kobasigawa, MD, professor of medicine at the UCLA Medical Center in Los Angeles and moderator of a press briefing at which the eplerenone study was discussed, told Medscape. "I believe that the results of the study will impact how we practice medicine. We will see greater use of this drug in a broader group of patients, especially younger patients."
Dr. Kobasigawa said the increased use of the drug relates to its adverse-effect profile: there was no excess gynecomastia or impotence associated with the drug. "This is very different from what we observe with spironolactone," he said.
"Those side effects occur about 10% of the time," says Inder Anand, MD, professor of medicine at the University of Minnesota in Minneapolis. But because heart failure occurs in older men and women for whom menstrual cycles and impotence may be moot, about 6% to 7% of patients may require a drug like eplerenone. He told Medscape that spironolactone costs about two cents a tablet while eplerenone may cost as much as $3 a pill. Dr. Anand was not involved in the study.
Dr. Pitt agreed that eplerenone is more expensive then spironolactone, but he said it was "pennies compared to cost of an implantable defibrillator. I could throw pills at patients all day and it wouldn't add up to the cost of an ICD," he told Medscape.
The trial enrolled 6,632 patients within 3 to 14 days after AMI. Entry criteria included a left ventricular ejection fraction of 40% or lower and heart failure documented by the presence of pulmonary rales, chest radiography, or the presence of a third heart sound.
Patients were randomly assigned to receive best available medical care — angiotensin-converting enzyme inhibitor and β-blocker — and eplerenone or placebo. Initial eplerenone dose was 25 mg, titrated to 50 mg.
Eplerenone at a mean dose of 43 mg was associated with a 15% decrease in total mortality, a 17% decrease in cardiovascular mortality, and a 21% decrease in sudden cardiac death. Total hospitalizations were 8% lower in the active treatment arm and hospitalizations for heart failure decreased by 15%.
There was, however, excess hyperkalemia, 5.5% in the eplerenone group vs. 3.9% in the placebo group. "Hyperkalemia is a concern and there was one death among patients with hyperkalemia but that death was in the placebo arm," said Dr. Pitt. Conversely, eplerenone was associated with a lower rate of hypokalemia, 8.4% vs. 13.1%.
During a follow-up of 16 months, there were 478 deaths in the eplerenone arm and 554 deaths in the placebo arm.
The study was funded by Pharmacia Corporation and Dr. Pitt is a consultant to Pharmacia.
ACC 52nd Annual Scientific Session: Late Breaking Clinical Trials I. Presented March 31, 2003.
N Engl J Med. 2003;348:1309-1321, 1380-1383
Reviewed by Gary D. Vogin, MD
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