Randomized, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Effect of Aldosterone Antagonism With Eplerenone on Ventricular Remodeling in Patients With Mild-to-Moderate Heart Failure and Left Ventricular Systolic Dysfunction.
Udelson, James E. MD; Feldman, Arthur M. MD, PhD; Greenberg, Barry MD; Pitt, Bertram MD; Mukherjee, Robin PhD; Solomon, Henry A. MD; Konstam, Marvin A. MD
Circulation: Heart Failure.
3(3):347-353, May 2010.
(Format: HTML, PDF)
Background-: Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF.
Methods and Results-: In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) <=35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy. Quantitative radionuclide ventriculograms to assess LV volumes and ejection fraction were performed at baseline and again after 9 months of double-blind treatment and were analyzed in a central core laboratory, blinded to treatment. The primary efficacy analysis was the between-group comparison of the change in LV end-diastolic volume index. Secondary analyses examined changes in LV end-systolic volume index and ejection fraction as well as markers of collagen turnover. Of the total 226 patients enrolled, 117 were randomly assigned to receive eplerenone and 109 to receive placebo. There was high use of contemporary background therapy at baseline, with >90% use of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers and >90% use of [beta]-blockers. Over 36 weeks of treatment, there was no apparent between-group difference in the changes in end-diastolic volume index or end-systolic volume index. There was a reduction in the collagen turnover marker procollagen type I N-terminal propeptide and plasma B-type natriuretic peptide in the eplerenone group compared with placebo (P=0.01 and P=0.04, respectively). There was no change in symptom status or quality-of-life measures.
Conclusions-: In a clinically stable, well-treated population of patients with mild-to-moderate HF symptoms and LV dysfunction, 36 weeks of treatment of aldosterone antagonism with eplerenone at a dose of 50 mg daily had no detectable effect on parameters of LV remodeling.
Clinical Trial Registration-: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00082589.
(C) 2010 American Heart Association, Inc.