CHICAGO – Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial session at the annual scientific sessions of the American Heart Association. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an "overwhelming benefit" with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

"We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice," said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincar? University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post-MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

"We have three trials in three distinct groups of heart failure severity which essentially have shown the same results," Dr. Zannad said in an interview. "This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers."

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure but that his enthusiasm is tempered by the risk of hyperkalemia. Aldosterone antagonists are known to change the sodium/potassium balance in patients with heart failure by increasing potassium levels. Raising the potassium to within the normal level benefits patients by reducing heart arrhythmias, but once potassium levels exceed the normal threshold of 5.5 mmol/L, raising potassium levels can independently promote arrhythmias and death.

11/15/10  

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FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION

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Vitals

Major Finding: Eplerenone reduced the risk of cardiovascular death or heart failure hospitalization by 37%, compared with placebo.

Data Source: Phase III randomized trial in 2,737 patients with NYHA class II heart failure.

Disclosures: EMPHASIS-HF was funded by Pfizer. Dr. Zannad reported receiving grants from and consulting for Pfizer. Two coauthors are Pfizer employees, and several others reported Pfizer grants and consultancy.

Links:

PEARL-HF trial

TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial

2010 Nov. 14; doi:10.1056/ NEJMoa1009492