title: Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study.
abstract: OBJECTIVE
  The purpose of this study was to analyze the incidence of new atrial fibrillation or flutter (AFF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) database.
  
  
  BACKGROUND
  Aldosterone antagonism in heart failure might influence atrial fibrosis and remodeling and, therefore, risk of developing AFF. The development of new AFF was a pre-specified secondary endpoint in the EMPHASIS-HF study.
  
  
  METHODS
  Patients in New York Heart Association functional class II and with ejection fraction ≤35% were eligible for EMPHASIS-HF. History of AFF at baseline was reported by investigators using the study case report form. New onset AFF (in those with no history of AFF at baseline) was reported using a specific endpoint form; in a sensitivity analysis we also examined the effect of eplerenone on AFF reported as an adverse event.
  
  
  RESULTS
  New onset AFF was significantly reduced by eplerenone: 25 of 911 (2.7%) versus 40 of 883 (4.5%) in the placebo group (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.35 to 0.96; p = 0.034). The reduction in the primary endpoint with eplerenone was similar among patients with and without AFF at baseline (HR: 0.60, 95% CI: 0.46 to 0.79 vs. HR: 0.70, 95% CI: 0.57 to 0.85, respectively; p for interaction = 0.41). The risk of cardiovascular (CV) death or hospital admission for worsening heart failure, the primary endpoint, was not significantly different in subjects with and without AFF at baseline (both study groups combined: HR: 1.23, 95% CI: 0.81 to 1.86; p = 0.33).
  
  
  CONCLUSIONS
  In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF. The effects of eplerenone on the reduction of major CV events were similar in patients with and without AFF at baseline.
authors.affiliation: Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden. Karl.swedberg@gu.se.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
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: Harry
authors.initials: H
authors.lastname: Shi
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D000077545:Eplerenone; D005260:Female; D054143:Heart Failure, Systolic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D011379:Prognosis; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone