PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the annual congress of the European Society of Cardiology.

"Overall efficacy, no matter where we looked, was about the same, and we had the same safety," he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study closure, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66, P value less than .0001), said Dr. Pitt, with the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62, P less than .001).

"This suggests, to us at least, that this is going to have important cost implications, quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival," he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A_1C and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was better than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54, P value less than .0001).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European guidelines for aldosterone blockade don’t specify a particular agent, but look at the agents as a class.

"We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes," he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m², the improvement in the primary outcome reached 38% with eplerenone over placebo (HR, 0.62, P = .0001).

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m² in an attempt to minimize the risk of hyperkalemia. Despite this, the positive results remain applicable, Dr. Pitt said in an interview.

08/29/11  

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FROM THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY

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Vitals

Major Finding: Among patients with diabetes who took eplerenone, there was a 46% reduction in the primary end point of death from cardiovascular causes or heart failure hospitalization, compared with those who took placebo.

Data Source: Subanalysis of high-risk groups and follow-up analyses of the phase III EMPHASIS-HF trial.

Disclosures: Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.