title: Eplerenone and new-onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).
abstract: OBJECTIVE
  No studies have examined the effect of mineralocorticoid receptor antagonist therapy on new-onset diabetes. In addition, though the combination of diabetes and chronic heart failure (CHF) carries a poor prognosis, few studies have examined predictors of new-onset diabetes in those with CHF.
  
  
  RESULTS
  In patients with symptomatically mild CHF who participated in the placebo-controlled Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure, we examined the effect of the aldosterone antagonist, eplerenone, on physician-diagnosed diabetes using univariate Cox proportional hazard analysis. To identify predictors of new-onset diabetes (measures of glycaemia were not available), data from trial arms were combined and multivariate Cox proportional hazard analyses and receiver operating characteristic curve analyses were conducted. At baseline, the mean age of 1846 initially non-diabetic patients was 69 years and mean left ventricular ejection fraction was 26%. Over 21 months, 69 (3.7%) developed diabetes (33 on eplerenone, 36 on placebo). Eplerenone had no effect on new-onset diabetes [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.59-1.52] and no effect on the composite of new-onset diabetes or mortality (HR 0.80, 95% CI 0.64-1.01). Independent predictors of new-onset diabetes included digoxin therapy, higher serum alanine aminotransferase, longer duration of heart failure, current or previous smoker, higher waist circumference, lower age, and higher systolic blood pressure with a combined c-statistic of 0.74.
  
  
  CONCLUSIONS
  Eplerenone had no effect on new-onset diabetes in patients with CHF, but further large-scale studies are required to address this question comprehensively. Commonly recorded parameters provided useful information for predicting new-onset diabetes.
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: David
authors.initials: D
authors.lastname: Preiss
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
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
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D003920:Diabetes Mellitus / Q000473:pathology*; D000077545:Eplerenone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D006760:Hospitalization; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone