Aims: Aldosterone antagonism reduces cardiovascular morbidity and mortality in patients with left ventricular (LV) systolic dysfunction and heart failure or diabetes after acute myocardial infarction (AMI). The mechanism of this effect is unclear. We performed a contrast-enhanced cardiac magnetic resonance study to assess the effects of eplerenone on LV remodeling after AMI.
Methods: One hundred patients (mean age, 58.9 +/- 12 years; 77% male) with LV systolic dysfunction but without heart failure or diabetes were randomized to 24 weeks' double-blind treatment with eplerenone or placebo started 1 to 14 days after AMI. Contrast-enhanced cardiac magnetic resonance was performed, and plasma concentrations of matrix metalloproteinase-2 (MMP-2) and MMP-9 were measured before randomization and at 12 and 24 weeks.
Results: Baseline LV ejection fraction was, by chance, significantly higher in eplerenone than in placebo-treated patients. Eplerenone had no effect on the primary end point (change in LV end-systolic volume index); after covariate adjustment, the primary end point fell by 6.1 +/- 2.7 mL/m2 with eplerenone compared to placebo (P = .027), and LV end-diastolic volume index fell by 7.5 +/- 3.4 mL/m2 (P = .031); eplerenone did not significantly influence LV ejection fraction. Eplerenone, after covariate adjustment, significantly decreased MMP-2 and increased MMP-9 over 24 weeks relative to placebo.
Conclusions: In a population of patients with AMI with high uptake of contemporary antiremodeling therapy, eplerenone provides modest incremental protection against LV remodeling, only after covariate adjustment.
Trial registration: ClinicalTrials.gov NCT00132093.