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Increased Mortality Associated With Digoxin in Contemporary Patients With Atrial Fibrillation
Open accessAbstract
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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“Observational studies have associated digoxin use with excess mortality in AF patients, [547][548][549] but this association is likely due to selection and prescription biases rather than harm caused by digoxin, [550][551][552][553] particularly as digoxin is commonly prescribed to sicker patients.225”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [547]
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Metadata
- Authors
- Turakhia, M. P., Santangeli, P., Winkelmayer, W. C., Xu, X., Ullal, A. J., Than, C. T., Schmitt, S., Holmes, T. H., Frayne, S. M., Phibbs, C. S., Yang, F., Hoang, D. D., Ho, P. M., & Heidenreich, P. A.
- Affiliations
- VA Palo Alto Health Care System (US)
- Stanford Medicine (US)
- Maimonides Medical Center (US)
- VA Eastern Colorado Health Care System (US)
- Corresponding author
- Turakhia, Mintu P.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 64
- Issue
- 7
- Pages
- 660-668
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC4405246
- OpenAlex
- W2157998686
- Cited by
- 208
- References
- 31
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 12 · 2021: 18 · 2020: 17 · 2019: 19 · 2018: 11 · 2017: 21 · 2016: 37 · 2015: 41 · 2014: 9
- FWCI
- 24.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (09SDG2250647, CDA09027-1)
- Amgen
- GlaxoSmithKline
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095024)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- digoxin, atrial fibrillation, mortality, drug safety, newly diagnosed atrial fibrillation, non-valvular atrial fibrillation, medication adherence, veterans, propensity score matching, beta-blockers, amiodarone, warfarin
- MeSH terms
- Aged, Anti-Arrhythmia Agents, Atrial Fibrillation, Cause of Death, Digoxin, Female, Follow-Up Studies, Humans, Male, Outpatients, Prognosis, Retrospective Studies, Risk Factors, United States, Survival Rate, Confidence Intervals, Proportional Hazards Models, Risk Assessment, Propensity Score
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