Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation
Abstract
BACKGROUND: The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established. METHODS AND RESULTS: We formed new-user cohorts of propensity score-matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67-0.96); intracranial hemorrhage, 0.34 (0.26-0.46); major gastrointestinal bleeding, 1.28 (1.14-1.44); acute myocardial infarction, 0.92 (0.78-1.08); and death, 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis. CONCLUSIONS: In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.
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There was a non-significant numerical increase in the rate of myocardial infarction with both dabigatran doses, which has not been replicated in large post-authorization analyses.
“There was a non-significant numerical increase in the rate of myocardial infarction with both dabigatran doses, 318,404 which has not been replicated in large post-authorization analyses.396”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [396]
Compared with warfarin, the risk of gastrointestinal bleeds was increased for dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, and edoxaban 60 mg once daily.
“Compared with warfarin, the risk of gastrointestinal bleeds was increased for dabigatran 150 mg twice daily, 396, 490 rivaroxaban 20 mg once daily, 491 and edoxaban 60 mg once daily.321”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [396]
Good data are available to support the use of anticoagulants in older patients from BAFTA, the NOAC trials, and analyses in elderly Americans (Medicare).
“Good data are available to support the use of anticoagulants in older patients from BAFTA (Birmingham Atrial Fibrillation Treatment of the Aged Study), 362 the NOAC trials, 39 and from analyses in elderly Americans (Medicare).396”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [396]
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- Authors
- Graham, D. J., Reichman, M. E., Wernecke, M., Zhang, R., Southworth, M. R., Levenson, M., Sheu, T.-C., Mott, K., Goulding, M. R., Houstoun, M., MaCurdy, T. E., Worrall, C., & Kelman, J. A.
- Affiliations
- United States Food and Drug Administration (US)
- ORCID
- Venue
- Circulation
- Published
- 2015-01-13
- Volume
- 131
- Issue
- 2
- Pages
- 157-164
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2063976695
- Cited by
- 644
- References
- 33
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 17 · 2023: 16 · 2022: 24 · 2021: 36 · 2020: 45 · 2019: 57 · 2018: 86 · 2017: 98 · 2016: 133 · 2015: 110 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 78.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- dabigatran, warfarin, non-valvular atrial fibrillation, elderly patients, Medicare, direct oral anticoagulants, ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, acute myocardial infarction, mortality, renal dysfunction, general practice
- MeSH terms
- Dabigatran, Aged, Aged, 80 and over, Anti-Arrhythmia Agents, Anticoagulants, Atrial Fibrillation, Benzimidazoles, Dose-Response Relationship, Drug, Follow-Up Studies, Medicare, Hemorrhage, Gastrointestinal Hemorrhage, Humans, Kidney Diseases, Retrospective Studies, Risk, Socioeconomic Factors, United States, Warfarin, beta-Alanine, Comorbidity, Proportional Hazards Models, Treatment Outcome, Intracranial Hemorrhages, Stroke, Kaplan-Meier Estimate
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