Aldosterone antagonists have proven beneficial in heart failure patients with moderate to severe symptoms and in MI patients with LV dysfunction and heart failure. Now the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) has extended these benefits to patients with systolic heart failure patients and mild symptoms.
EMPHASIS HF randomized 2737 patients with NYHA class II HF and an EF not over 35% to receive eplerenone or placebo in addition to standard therapy. The trial, which was presented at the AHA in Chicago and published simultaneously in the New England Journal of Medicine, was stopped early after 21 months. The rate of cardiovascular death or heart failure hospitalization was reduced from 25.9% in the placebo group to 18.3% in the eplerenone group (P<0.001). Total mortality was reduced from 15.5% to 12.5% (p<0.001). Hyperkalemia occurred significantly more often in the eplerenone group.
In an accompanying editorial, Paul Armstrong writes that the effect reported in EMPHASIS HF “seems surprisingly large for a trial of mildly symptomatic patients.” He points out that most of the trial participants were “heart disease veterans” at high risk and that few patients received ICD or CRT devices. Nevertheless, he states that with a number needed to treat of 19 to prevent one cardiovascular death or hospitalization and an NNT of 51 to prevent one death, the trial places “this therapy in the front rank of therapeutic choices.”
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Here is the press release from the AHA:
Eplerenone significantly improves survival in systolic heart failure patients with mild symptoms
- · Compared with placebo, the aldosterone receptor antagonist drug eplerenone reduced the combined risk of death and hospitalization by 37 percent among patients with mild heart failure.
- · Eplerenone also reduced the incidence of death and hospitalization due to any cause by more than one-third compared to placebo.
CHICAGO, Nov. 14, 2010 – 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 (Inspra) is in a class of drugs known as aldosterone antagonists. 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 blockages or narrowing of the arteries supplying the heart.
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.
Heart failure is a serious disease that affects almost six million adults in the United States. Although the heart continues to pump during heart failure, it is too weak to effectively circulate blood throughout the body. Early therapy is critical because untreated symptoms can worsen, and severe disease can be fatal.
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.