Digoxin Use in AF and Adverse CV Outcomes | Journal Scan

Study Questions:

Does digoxin increase the risk of adverse outcomes in patients with atrial fibrillation (AF)?


This was a post hoc analysis of the ROCKET AF trial, in which 14,171 patients with AF were randomly assigned to anticoagulation with rivaroxaban or warfarin. Outcomes were compared between patients who were and were not taking digoxin.


Digoxin was used in 5,239 patients (mean age 72 years). Patients taking digoxin were more often female (42% vs. 38%) and more often had heart failure (73% vs. 56%). Digoxin was independently associated with an increased risk of mortality (hazard ratio [HR], 1.17), vascular death (HR, 1.19), and sudden death (HR, 1.36). There were no interactions between heart failure and the higher risk of adverse outcomes in patients taking digoxin.


Digoxin independently increases the risk of all-cause mortality, vascular death, and sudden death in patients with AF.


Several retrospective studies have concluded that digoxin either does or does not increase the risk of negative outcomes in patients with AF. For example, two studies published online in November 2012 (Whitbeck, et al.) and April 2013 (Gheorghiade, et al.) in the European Heart Journal reported conflicting results. What makes these two studies notable is that they were based on analysis of exactly the same database (AFFIRM). These two studies provide compelling justification for skepticism of post hoc analyses in general. Nevertheless, because of the possibility that digoxin increases the risk of death, it would seem prudent to avoid its use in patients with AF unless all other options for rate control fail.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Atrial Fibrillation, Anticoagulants, Arrhythmias, Cardiac, Digoxin, Heart Failure, Risk, Warfarin, Death, Sudden, Mortality, Retrospective Studies, Secondary Prevention

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