Left ventricular remodeling after acute myocardial infarction: does eplerenone have an effect?
OBJECTIVE
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.
Weir
Robin A P
RA
Cardiology Department, Western Infirmary, Glasgow, Scotland, United Kingdom. robinweir75@hotmail.com
Mark
Patrick B
PB
Petrie
Colin J
CJ
Clements
Suzanne
S
Steedman
Tracey
T
Ford
Ian
I
Ng
Leong L
LL
Squire
Iain B
IB
Wagner
Galen S
GS
McMurray
John J V
JJ
Dargie
Henry J
HJ
D000368:Aged; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D000077545:Eplerenone; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000097:blood / Q000503:physiopathology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects*
D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9