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Risk of Bleeding With Single, Dual, or Triple Therapy With Warfarin, Aspirin, and Clopidogrel in Patients With Atrial Fibrillation
Abstract
BACKGROUND: Patients with atrial fibrillation (AF) often require anticoagulation and platelet inhibition, but data are limited on the bleeding risk of combination therapy. METHODS: We performed a cohort study using nationwide registries to identify all Danish patients surviving first-time hospitalization for AF between January 1, 1997, and December 31, 2006, and their posthospital therapy of warfarin, aspirin, clopidogrel, and combinations of these drugs. Cox proportional hazards models were used to estimate risks of nonfatal and fatal bleeding. RESULTS: A total of 82,854 of 118,606 patients (69.9%) surviving AF hospitalization had at least 1 prescription filled for warfarin, aspirin, or clopidogrel after discharge. During mean (SD) follow-up of 3.3 (2.6) years, 13,573 patients (11.4%) experienced a nonfatal or fatal bleeding. The crude incidence rate for bleeding was highest for dual clopidogrel and warfarin therapy (13.9% per patient-year) and triple therapy (15.7% per patient-year). Using warfarin monotherapy as a reference, the hazard ratio (95% confidence interval) for the combined end point was 0.93 (0.88-0.98) for aspirin, 1.06 (0.87-1.29) for clopidogrel, 1.66 (1.34-2.04) for aspirin-clopidogrel, 1.83 (1.72-1.96) for warfarin-aspirin, 3.08 (2.32-3.91) for warfarin-clopidogrel, and 3.70 (2.89-4.76) for warfarin-aspirin-clopidogrel. CONCLUSIONS: In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding. Dual warfarin and clopidogrel therapy and triple therapy carried a more than 3-fold higher risk than did warfarin monotherapy.
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“Approximately 15% of AF patients in contemporary trials 513 and registries [514][515][516] have a history of myocardial 1498 infarction.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [514]
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Metadata
- Authors
- Hansen, M. L., Sørensen, R., Clausen, M. T., Fog-Petersen, M. L., Raunsø, J., Gadsbøll, N., Gislason, G. H., Folke, F., Andersen, S. S., Schramm, T. K., Abildstrøm, S. Z., Poulsen, H. E., Køber, L., & Torp-Pedersen, C.
- Affiliations
- Copenhagen University Hospital (DK)
- ORCID
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2010-09-13
- Volume
- 170
- Issue
- 16
- Pages
- 1433-41
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2144471064
- Cited by
- 855
- References
- 45
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 23 · 2023: 25 · 2022: 41 · 2021: 37 · 2020: 64 · 2019: 83 · 2018: 63 · 2017: 75 · 2016: 80 · 2015: 68 · 2014: 63 · 2013: 76 · 2012: 63
- FWCI
- 42.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- atrial fibrillation, bleeding risk, warfarin, aspirin, clopidogrel, combination antithrombotic therapy, triple therapy, dual therapy, anticoagulation, platelet aggregation inhibition, fatal bleeding
- MeSH terms
- Clopidogrel, Aged, Anticoagulants, Aspirin, Atrial Fibrillation, Brain Ischemia, Denmark, Drug Therapy, Combination, Female, Hemorrhage, Humans, Male, Registries, Risk, Ticlopidine, Warfarin, Cohort Studies, Comorbidity, Incidence, Proportional Hazards Models, Stroke
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