title: Clinical benefits of eplerenone in patients with systolic heart failure and mild symptoms when initiated shortly after hospital discharge: analysis from the EMPHASIS-HF trial.
abstract: OBJECTIVE
  Cardiovascular hospitalization (CVH) in patients with heart failure (HF) is associated with a high post-discharge rate of early re-admission and CV death. Eplerenone might be effective in reducing the incidence of these adverse clinical outcomes during this period.
  
  
  RESULTS
  The EMPHASIS-HF trial compared eplerenone with placebo added to standard therapy in 2737 patients with New York Heart Association class II HF and left ventricular ejection fraction ≤35%. We conducted a post hoc analysis in the 2338 patients randomized within 180 days of a CVH. The interaction between the time from the qualifying CVH to randomization and the primary outcome of CV death or hospitalization for HF (HHF), as well as other secondary outcomes, was assessed in Cox survival models. Most of the qualifying CVHs were HHF (N = 1496, 64.0%), acute coronary syndromes (N = 390, 16.7%), and arrhythmias (N = 197, 7.2%). The median time of study drug initiation from qualifying CVH was 42 days. The relative rate reductions in CV death/HHF, HHF, and all-cause mortality were similar (P for interaction = 0.65, 0.44, and 0.40, respectively) whether the treatment was initiated <42 or 42+ days after qualifying CVH. Absolute rate reductions were -5.61 [-8.67, -2.55] events per 100 patient × years in the <42 days group and -3.58 [-6.37, -0.79] in the 42+ days group. The adverse effects of eplerenone were also unaffected by the time from the qualifying CVH.
  
  
  CONCLUSIONS
  Eplerenone is safe, improves survival, and may prevent re-admission when initiated soon after a hospitalization for HF or acute coronary syndromes in patients with systolic HF and mild symptoms.
authors.affiliation: INSERM, Centre D'Investigations Cliniques 9501, Université de Lorraine, CHU de Nancy, Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu, 4 Rue du Morvan, 54500 Vandoeuvre lès Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girerd
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Collier
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.affiliation: Center of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: The British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, Goteborg, Sweden National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.affiliation: Pfizer, New York, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.affiliation: School of Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: INSERM, Centre D'Investigations Cliniques 9501, Université de Lorraine, CHU de Nancy, Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu, 4 Rue du Morvan, 54500 Vandoeuvre lès Nancy, France f.zannad@chu-nancy.fr.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality / Q000517:prevention & control; D000368:Aged; D000077545:Eplerenone; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D010359:Patient Readmission; D055502:Secondary Prevention; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
keywords: EMPHASIS-HF; Eplerenone; Hospitalization; Systolic heart failure; Timing; Treatment effect