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

Background: Some evidences suggest that the use of digoxin may be harmful in atrial 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 33.2 months (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 b 0.001) and at higher risk of thromboembolic events (p b 0.001).No difference in TTR between the two groupswas 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 b 0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p b 0.001) and CV death (HR: 4.686, p b 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 usewas associated with a higher rate of total and CV mortality.