Cited by 855Atrial Fibrillation Management and OutcomesAntiplatelet Therapy and Cardiovascular DiseasesBlood Coagulation and Thrombosis Mechanisms

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Risk of Bleeding With Single, Dual, or Triple Therapy With Warfarin, Aspirin, and Clopidogrel in Patients With Atrial Fibrillation

Hansen, Morten L., Sørensen, Rikke, Clausen, Mette T., Fog-Petersen, Marie Louise, Raunsø, Jakob, Gadsbøll, Niels, Gislason, Gunnar H., Folke, Fredrik, Andersen, Søren S., Schramm, Tina K., Abildstrøm, Steen Z., Poulsen, Henrik E., Køber, Lars, Torp-Pedersen, Christian·2010·Archives of Internal Medicine

DOI 10.1001/archinternmed.2010.271

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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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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: Hansen, Morten L.
Sørensen, Rikke
Raunsø, Jakob
Gislason, Gunnar H.
Folke, Fredrik
Poulsen, Henrik E.
Køber, Lars
Torp-Pedersen, Christian
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)
DOI: 10.1001/archinternmed.2010.271
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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Risk of Bleeding With Single, Dual, or Triple Therapy With Warfarin, Aspirin, and Clopidogrel in Patients With Atrial Fibrillation

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