Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.
BACKGROUND
Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double-blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.


METHODS
Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3319 patients) or placebo (3313 patients) [correction] in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia.


RESULTS
During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P=0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P=0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001).


CONCLUSIONS
The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.
Pitt
Bertram
B
University of Michigan, Ann Arbor, USA. bpitt@umich.edu
Remme
Willem
W
Zannad
Faiez
F
Neaton
James
J
Martinez
Felipe
F
Roniker
Barbara
B
Bittman
Richard
R
Hurley
Steve
S
Kleiman
Jay
J
Gatlin
Marjorie
M
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004311:Double-Blind Method; D000077545:Eplerenone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011188:Potassium / Q000097:blood; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D011188:Potassium