Patients with systolic heart failure and mild symptoms given eplerenone had a 37 percent reduced combined risk of death and hospitalization than patients who received a placebo, according to late-breaking clinical trial results presented at the American Heart Association's Scientific Sessions 2010.

In the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF), 2,737 patients with mild heart failure were randomized to receive eplerenone (25-50 milligrams) or placebo, as well as standard heart failure therapy. Among patients taking eplerenone, 249 deaths or hospitalizations occurred, compared to 356 in the placebo group - a statistically significant difference.

Eplerenone is in an aldosterone antagonist. These medications improve the remodeling of the failing heart by blocking the action of aldosterone, a naturally occurring hormone that was initially found to help maintain appropriate amounts of salt and water in the body. However, aldosterone can also have a number of direct harmful effects on the cardiovascular system. Aldosterone concentrations are abnormally high in people with heart failure.

Under current guidelines, aldosterone antagonists, including eplerenone and the older spironolactone, are recommended only for patients with moderate to severe heart failure and reduced heart function or for patients with heart failure following a recent heart attack. Until this study, their effects in patients with mild disease were unclear.

"This treatment is certainly going to change the guidelines for mild heart failure," said Faiez Zannad, M.D., Ph.D., the study's lead author and professor of therapeutics and director of the Clinical Investigation Center at the Nancy University Hospital Center in Nancy, France. "Now patients with all kinds of severity of systolic heart failure, whether it is post-myocardial infarction, with mild or severe symptoms, are potentially eligible for some kind of aldosterone blockade, and, certainly, for eplerenone."

In the study, eplerenone also decreased the rate of a number of other complications. It's also important that eplerenone reduced the number of deaths due to any cause and hospitalizations for any reason, by one-third compared to placebo, Zannad said.

"What was impressive was that we also hit all the secondary endpoints, including mortality from all causes," he said.

Study participants' average age was 69 years, 78 percent were male, and 82 percent were white. Most had suffered from heart failure for several years, with an average duration of nearly five years. Two-thirds had a history of atherosclerosis.

Patient enrollment began in March 2006 at 270 centers in 29 countries. Average follow-up was 21 months. Enrollment ended before the scheduled end of the study, in May 2010, because eplerenone showed an overwhelming benefit in reducing heart-failure deaths and hospitalizations.

Co-authors are John J.V. McMurray, M.D.; Henry Krum, Ph.D.; Dirk J. van Veldhuisen, M.D., Ph.D.; Karl Swedberg, M.D., Ph.D.; Harry Shi, M.S.; John Vincent, M.B., Ph.D.; Stuart J Pocock, Ph.D.; and Bertram Pitt, M.D. Author disclosures are on the abstract.

Pfizer, Inc. funded the study.