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Selective Aldosterone Blockade Reduces Heart Failure Mortality After Myocardial Infarction: Presented at HF

By Douglas Reynolds

STRASBOURG, FRANCE -- June 23, 2003 -- A large trial has shown that patients with acute myocardial infarction (AMI), complicated by left ventricular dysfunction and heart failure, are at lower risk of morbidity and mortality if their medical therapy is combined with the new generation aldosterone inhibitor, eplerenone.

The results, from the Eplerenone Post-AMI Heart Failure Efficacy and Survival (EPHESUS) trial, were presented here June 23^rd during the late breaking trials session at the Heart Failure 2003 conference, sponsored by the European Society of Cardiology, and the International Society for Heart Research.

The neurohormonal hypothesis suggests that more comprehensive blockade is beneficial for treating patients with left ventricular dysfunction, according to presenter and investigator Willem Remme, MD, STICARES Cardiovascular Research Foundation, Rhoon, Netherlands. In a previous trial, the aldosterone inhibitor, spironolactone, improved survival in advanced heart failure patients, but induced a number of side effects such as gynecomastia and hyperkalemia.

Eplerenone is a selective aldosterone receptor antagonist that blocks the mineralcorticoid receptors without affecting glucocorticoid, progesterone, or androgen receptors, thus avoiding the hormonal side effects associated with spironolactone (a non-selective aldosterone antagonist).

The researchers enrolled a total of 6632 patients who had suffered an AMI, had left ventricular ejection fraction of 40% or less, and rales. They randomized 3319 to receive 25 mg to 50 mg of eplerenone, and 3213 to placebo. All patients also received optimal medical treatment, which included an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), beta blockers, aspirin, statin, and reperfusion therapy.

All-cause mortality in the eplerenone arm was significantly decreased in the eplerenone group compared, to the placebo group (14.4% versus 16.7%, P=.03). The relative risk reduction was 15%.

Incidence of another study end point -- death or hospitalization for cardiac causes -- was reduced by 13% with eplerenone compared to placebo, and sudden cardiac death was also significantly reduced by 21% in the eplerenone group.

Subgroup analysis demonstrated that this effect was consistent across the groups. Treating 50 patients with eplerenone would save 1 life within 1 year, while treating 33 patients would prevent at least 1 cardiovascular death or hospitalization in 1 year. "Of special mention," said Dr. Remme, "was the finding that eplerenone's benefits were most apparent in patients already treated with beta-blockade, and either an ACE inhibitor or an ARB."

"There was no report of excessive gynecomastia, impotence, or menstrual disorder," he said. Hyperkalemia was increased by 1.6%, and hypokalemia was reduced by 4.7%.

The results were published in the April 3, 2003 New England Journal of Medicine (2003;348:1309-21).


[Study title: Eplerenone, a Selective Aldosterone Blocker, in Patients With Left Ventricular Dysfunction After Myocardial Infarction. Late breaking abstract EPHESUS]

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