title: Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: An analysis of the Digitalis Investigation Group (DIG) trial.
abstract: BACKGROUND
  Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status.
  
  
  METHODS
  We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment.
  
  
  RESULTS
  Of the 6800 patients, those with diabetes (n=1933) were older, more often women, had worse clinical status and more co-morbidity than those without diabetes. All-cause and CV mortality were higher in patients with diabetes than in those without and digoxin did not reduce mortality in either sub-group. The rate of HF hospitalization (per 100 person-years) in patients with diabetes was higher than in those without and was reduced by digoxin in both patient groups: diabetes - placebo 20.5 and digoxin 16.0 (HR 0.79, 95% CI: 0.68-0.91); no diabetes - placebo 12.7 and digoxin 8.7 (HR 0.69, 0.62-0.77); interaction p=0.14. Suspected digoxin toxicity in patients randomised to digoxin was more common among patients with diabetes than without (6.5% versus 5.8%), as was hospitalisation for digoxin toxicity (1.4% versus 0.8%).
  
  
  CONCLUSIONS
  Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
authors.forename: Azmil H
authors.initials: AH
authors.lastname: Abdul-Rahim
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: MacIsaac
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: Golden Jubilee National Hospital, Glasgow, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Petrie
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK. Electronic address: john.mcmurray@glasgow.ac.uk.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D004070:Digitalis; D004077:Digoxin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D006760:Hospitalization / Q000639:trends; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin
keywords: Diabetes; Digoxin; Heart failure; Outcome