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Publication Briefs

Study Shows Digoxin Significantly Associated with Increased Risk of Death among Veterans with Atrial Fibrillation

Digoxin is widely used to control the ventricular rate in patients with atrial fibrillation/atrial flutter (AF). Despite the lack of randomized trials of digoxin in AF cohorts, clinical guidelines currently endorse its use for patients with AF. Therefore, this study investigated the association of digoxin therapy with mortality in a large cohort of Veterans with AF. The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study is a retrospective cohort of Veterans newly diagnosed with AF and treated within the VA healthcare system. Using VA data, investigators identified 122,465 Veterans (mean age of 72 years; 98% male) with newly diagnosed, non-valvular AF who were seen in a VA outpatient care setting between FY04 and FY08. Investigators assessed receipt of outpatient digoxin within 90 days following the index AF diagnosis, and the primary outcome was time to death beginning 90 days after AF diagnosis. Variables included patient demographics, comorbidities, receipt of concomitant drug therapies, drug adherence, and kidney function.


  • Among Veterans with newly diagnosed AF, treatment with digoxin was significantly and independently associated with increased risk of death, regardless of age, gender, kidney function, heart failure status, concomitant therapies, or drug adherence.
  • Of the 122,465 Veterans in the study, 28,679 (23%) received digoxin. Compared with non-recipients, digoxin recipients had a higher prevalence of heart failure (HF) and receipt of beta-blockers, angiotensin receptor blockers, antiplatelet therapy, diuretic agents, and warfarin.
  • Using propensity-matched analysis, digoxin increased the risk of death by 1.21 times compared to comparable patients treated with other therapies for AF. Robust sensitivity analyses indicated that it would be improbable for an unidentified confounder (such as frailty or heart failure severity) to explain the result.


  • Because AF is a progressive disease, the choice to include patients with new (incident) AF could limit generalizability of study findings in prevalent AF cohorts.
  • Investigators could not measure HF severity on the basis of symptom class, ejection fraction, or HF hospitalizations.
  • All-cause mortality was used rather than cause-specific mortality, which could prevent a more meaningful determination of how drug exposure may have led to death.


  • While these findings challenge current cardiovascular society recommendations, the implication is not that every patient should come off this drug and every doctor should stop using it. Rather, physicians should consider alternatives to digoxin in managing patients with AF as it may still have a useful role under specific and carefully monitored conditions.

This study was partly funded by HSR&D (IIR 09-092). Dr. Turakhia is also supported by an HSR&D Career Development Award and is part of the VA Palo Alto Health Care System.

PubMed Logo Turakhia M, Santangeli P, Winkelmayer W, et al. Increased Mortality Associated with Digoxin in Contemporary Patients with Atrial Fibrillation. Journal of the American College of Cardiology. August 19, 2014;64(7):660-668.

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