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

Abstract

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.