Home > atrial fibrillation, Journal Club > Journal Club 22 October 2014

Journal Club 22 October 2014


Increased Mortality Associated With Digoxin in Contemporary Patients With Atrial Fibrillation Findings From the TREAT-AF Study





Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in
atrial fibrillation/flutter (AF).


The goal of this study was to evaluate the association of digoxin with mortality in AF.
METHODS Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF)
study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed,
nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate
and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual
confounding was assessed by sensitivity analysis.


Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 10.3 years, 98.4% male), 28,679
(23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated
patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after
multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity
matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not
modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin.


Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent
of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge
current cardiovascular society recommendations on use of digoxin in AF.

Supplementary Material

AFFIRM study
AFFIRM subset
AFFIRM subset editorial

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