Mintu P Turakhia1, Pasquale Santangeli2, Wolfgang C Winkelmayer3, Xiangyan Xu4, Aditya J Ullal4, Claire T Than4, Susan Schmitt4, Tyson H Holmes5, Susan M Frayne6, Ciaran S Phibbs7, Felix Yang8, Donald D Hoang4, P Michael Ho9, Paul A Heidenreich10. 1. Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California. Electronic address: mintu@stanford.edu. 2. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California; Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 3. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California. 4. Veterans Affairs Palo Alto Health Care System, Palo Alto, California. 5. Stanford Center for Sleep Sciences & Medicine, Division of Sleep Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California. 6. Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Division of General Internal Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California. 7. Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California. 8. Maimonides Heart & Vascular Center, New York, New York. 9. Veterans Affairs Eastern Colorado Health Care System, Denver, Colorado; Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado. 10. Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Abstract
BACKGROUND: Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). OBJECTIVES: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). OBJECTIVES: 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. RESULTS: 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. CONCLUSIONS: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.
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