Does Digoxin Increase Risks of Adverse CV Outcomes in AF Patients?

Journal Wrap | Does digoxin increase the risk of adverse outcomes in patients with atrial fibrillation (AF)? A post hoc analysis of the ROCKET AF trial, in which 14,171 patients with AF were randomly assigned to anticoagulation therapy with rivaroxaban or warfarin, suggests it does.

In the analysis, published in the Lancet, outcomes were compared between patients who were and were not taking digoxin. Of the 5,239 patients (mean age 72 years) taking digoxin, most were female (42% vs. 38%) and most had heart failure (73% vs. 56%).

Overall results showed that digoxin was independently associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.17), vascular death (HR, 1.19), and sudden death (HR, 1.36) in AF patients. There were no interactions between heart failure and the higher risk of adverse outcomes in patients taking digoxin.

In a separate ACC Journal Scan, Fred Morady, MD, notes that 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. However, he determined that "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."


  1. Washam JB, Stevens SR, Lokhnygina Y, et al. Lancet. 2015;doi:10.1016/S0140-6736(14)61836-5.

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