Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure.
OBJECTIVE
This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) < or =40% and clinical signs of heart failure.


BACKGROUND
In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF < or =40% and clinical signs of heart failure.


METHODS
We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial.


RESULTS
At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003) and the risk of sudden cardiac death by 37% (p = 0.051).


CONCLUSIONS
Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF < or =40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.
Pitt
Bertram
B
University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA. bpitt@med.umich.edu
White
Harvey
H
Nicolau
Jose
J
Martinez
Felipe
F
Gheorghiade
Mihai
M
Aschermann
Michael
M
van Veldhuisen
Dirk J
DJ
Zannad
Faiez
F
Krum
Henry
H
Mukherjee
Robin
R
Vincent
John
J
D000368:Aged; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000077545:Eplerenone; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality*; D011336:Probability; D016016:Proportional Hazards Models; D012016:Reference Values; D012720:Severity of Illness Index; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000175:diagnosis / Q000401:mortality*
D013148:Spironolactone; D000077545:Eplerenone