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

Study Questions:

Does digoxin use increase mortality in patients with newly diagnosed atrial fibrillation (AF)?


In the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) retrospective study, patients with newly diagnosed, nonvalvular AF or atrial flutter during an inpatient or outpatient encounter in the Veterans Affairs (VA) health system were identified. Multivariate and propensity-matched Cox proportional hazards were used to evaluate the association between digoxin use and mortality. Sensitivity analysis was performed to help account for unmeasured confounders.


Among 122,465 patients (ages 72.1 ± 10.3 years; 98% males) with newly diagnosed AF, 28,679 patients (23%) received digoxin. Cumulative mortality was higher for patients who were prescribed digoxin than those who were not (95 vs. 67 per 1,000 person-years; p < 0.001). After multivariate analysis, digoxin use was found to be independently associated with mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.23-1.29; p < 0.001). The effect remained after propensity matching (HR, 1.21; 95% CI, 1.17-1.25; p < 0.001) and adjusting for drug adherence. The risk of death was not influenced by variables such as age, heart failure, renal function, oral anticoagulation, or concomitant antiarrhythmic use.


The authors concluded that digoxin use is associated with increased mortality in patients with newly diagnosed AF.


Digoxin, despite being commonly used, is not usually considered first-line therapy for rate control in patients with AF. However, in patients with heart failure, its use did receive a Class I recommendation in the most recent AF guideline document. Prior studies have reached conflicting conclusions, even when the analyses were performed on the same data set (e.g., AFFIRM trial). Obviously a nonrandomized study cannot be considered definitive. But the sample size (>100,000 patients) and the statistical rigor are notable strengths of the study. From a practical standpoint, in patients with newly diagnosed AF, it is reasonable to consider digoxin only after exhausting other options, such as beta- and calcium-channel blocker therapy, if at all.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Multivariate Analysis, Digoxin, Heart Failure, Atrial Flutter

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