title: Eplerenone in patients with systolic heart failure and mild symptoms.
abstract: BACKGROUND
  Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms.
  
  
  METHODS
  In this randomized, double-blind trial, we randomly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.
  
  
  RESULTS
  The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P=0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001).
  
  
  CONCLUSIONS
  Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms. (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.).
authors.affiliation: INSERM, Centre d'Investigation Clinique 9501 and Unité 961, and the Department of Cardiology, Nancy University, Nancy, France. f.zannad@chu-nancy.fr
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Harry
authors.initials: H
authors.lastname: Shi
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000368:Aged; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000401:mortality; D003131:Combined Modality Therapy; D017147:Defibrillators, Implantable; D004311:Double-Blind Method; D000077545:Eplerenone; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D002317:Cardiovascular Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone