title: Eplerenone in patients with systolic heart failure and mild symptoms: analysis of repeat hospitalizations.
abstract: BACKGROUND
  Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits.
  
  
  RESULTS
  The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08-3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42-0.66; P<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings.
  
  
  CONCLUSIONS
  Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Rogers
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
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: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000368:Aged; D000077545:Eplerenone; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D012044:Regression Analysis; D012307:Risk Factors; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone