Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial Fibrillation Cohort

Abstract

Background: Although digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.

Objectives: This study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes.

Methods: Longitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.

Results: Among 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p < 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99).

Conclusions: After adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxin's safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed.

Keywords: heart failure; mortality; patient outcome assessment; safety.

CENTRAL ILLUSTRATION Association of Digoxin Use with Subsequent Outcomes

In this assessment of longitudinal patterns of digoxin use in patients with atrial fibrillation (AF) with and without heart failure (HF), registry data were used to correlate digoxin use with outcomes. Among patients receiving digoxin at study enrollment (prevalent), digoxin use was not associated with subsequent onset of symptoms, hospitalization, or mortality in patients with (A) or without (B) HF. The same is true for patients with HF who initiated digoxin during follow-up (C), although incident digoxin use in patients without HF was associated with subsequent death (D). CI = confidence interval; CV = cardiovascular; HR = hazard ratio.