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 trial (DIG)

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 hospitalisation (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.