Eplerenone reduces risk of death and hospitalization in patients with mildly symptomatic heart failure

Key Points

Patients with systolic heart failure and mild symptomatology [New York Heart Association (NYHA) class II] taking the mineralocorticoid receptor antagonist-eplerenone-experienced a 37% reduction in death from cardiovascular causes or first hospitalization for heart failure, researchers demonstrated in a new study.

The study, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), was published on the New England Journal of Medicine website.

"Activation of the mineralocorticoid receptor by both aldosterone and cortisol plays an important role in the pathophysiology of heart failure, and mineralocorticoid receptors are overexpressed in the failing heart," noted researchers in their paper.

To test their hypothesis that the addition of a mineralocorticoid antagonist to current standard-of-care resulted in better outcomes in patients with mild heart failure, researchers randomly assigned 2,737 patients with NYHA class II heart failure and an ejection fraction ≤35% to receive eplerenone up to 50 mg daily or placebo, in addition to standard therapy (93% receiving an ACE inhibitor, ARB, or both; 87% a beta-blocker; 85% a diuretic; 26% digoxin; and 62% a lipid-lowering agent).

The trial was stopped prematurely, according to pre-specified rules, after a median follow-up of 21 months. The primary outcome of death from cardiovascular causes or first hospitalization for heart failure occurred less commonly in the eplerenone group (HR, 0.63; 95% CI, 0.54 to 0.74; P<.001). Moreover, fewer patients receiving eplerenone died for any reason (HR, 0.76; 95% CI, 0.62 to 0.93; P=.008) or due to cardiovascular causes (HR, 0.76; 95% CI, 0.61 to 0.94; P=.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone.

"The effect on death from cardiovascular causes or hospitalization for heart failure translates into an impressively low number needed to treat: 19 patients," noted Dr Paul W. Armstrong, MD, FRCP(C), from the University of Alberta in Edmonton, Canada, in an accompanying editorial. He continued, "The number needed to treat to prevent one death is 51 patients, positioning this therapy in the front rank of therapeutic choices."

However, eplerenone use was not without significant adverse effects. In particular, a serum potassium level >5.5 mmol/L occurred in 11.8% of patients in the eplerenone group compared to 7.2% in the placebo group (P<.001).

Approximately 5.8 million people in the United States have heart failure and about 670,000 Americans are diagnosed with it each year. Of these, 1 in 5 will die within 1 year from diagnosis.

SOURCES

Zannad F, McMurray JJV, Krum H; for the EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. DOI: 10.1056/NEJMoa1009492.

Armstrong PW. Aldosterone Antagonists - Last Man Standing? N Engl J Med. 2011. DOI:10.1056/NEJMe1012547.

American Heart Association. Heart Disease and Stroke Statistics – 2010 Update. Dallas, Texas: American Heart Association; 2010. Available at: http://www.americanheart.org/downloadable/heart/1265665152970DS-3241%20HeartStrokeUpdate_2010.pdf. Accessed November 15, 2010.