Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation

Int J Cardiol. 2015 Feb 1;180:1-5. doi: 10.1016/j.ijcard.2014.11.112. Epub 2014 Nov 18.


Background: Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality.

Methods: Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality.

Results: Median follow-up was 33.2months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p=0.007), with a clinical history of HF (p<0.001) and at higher risk of thromboembolic events (p<0.001). No difference in TTR between the two groups was registered (p=0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p<0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p<0.001) and CV death (HR: 4.686, p<0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p=0.0263) and CV death (HR: 4.043, p=0.004).

Conclusions: In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality.

Keywords: Anticoagulation; Atrial fibrillation; Digoxin; Mortality; Time in therapeutic range.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Cause of Death / trends
  • Digoxin / adverse effects*
  • Digoxin / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heart Failure / drug therapy
  • Heart Failure / mortality*
  • Humans
  • Italy / epidemiology
  • Male
  • Propensity Score
  • Prospective Studies
  • Risk Assessment*
  • Risk Factors
  • Stroke / mortality*
  • Stroke / prevention & control
  • Survival Rate / trends


  • Anti-Arrhythmia Agents
  • Anticoagulants
  • Digoxin