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

Int J Cardiol. 2016 Apr 15:209:310-6. doi: 10.1016/j.ijcard.2016.02.074. Epub 2016 Feb 8.

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%).

Conclusion: Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity.

Keywords: Diabetes; Digoxin; Heart failure; Outcome.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / physiopathology
  • Digitalis*
  • Digoxin / adverse effects
  • Digoxin / pharmacology
  • Digoxin / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology
  • Heart Failure / physiopathology*
  • Hospitalization / trends
  • Humans
  • Hyperkalemia / chemically induced
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Stroke Volume / drug effects*
  • Stroke Volume / physiology
  • Treatment Outcome

Substances

  • Cardiotonic Agents
  • Digoxin