Major Bleeding in Patients With Atrial Fibrillation Receiving Apixaban or Warfarin
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Objectives This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding.Background Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.Methods All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model.Results The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk.Conclusions Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage.
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Rates of haemorrhagic stroke and intracranial haemorrhage, but not of ischaemic stroke, were lower on apixaban than on warfarin.
“Rates of haemorrhagic stroke and intracranial haemorrhage, but not of ischaemic stroke, were lower on apixaban.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [402]
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
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- Authors
- Hylek, E. M., Held, C., Alexander, J. H., Lopes, R. D., De Caterina, R., Wojdyla, D. M., Huber, K., Jansky, P., Steg, P. G., Hanna, M., Thomas, L., Wallentin, L., & Granger, C. B.
- Affiliations
- Boston University (US)
- Uppsala University (SE)
- Duke Medical Center (US)
- Wilhelminen Hospital (AT)
- Bristol-Myers Squibb (United States) (US)
- Corresponding author
- Hylek, Elaine M.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 63
- Issue
- 20
- Pages
- 2141-2147
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2010861397
- Cited by
- 344
- References
- 28
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 21 · 2023: 14 · 2022: 13 · 2021: 28 · 2020: 29 · 2019: 32 · 2018: 33 · 2017: 33 · 2016: 59 · 2015: 47 · 2014: 14 · 2013: 1
- FWCI
- 34.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- Bristol-Myers Squibb and Pfizer
- AstraZeneca, Merck, GlaxoSmithKline, Roche, and Bristol-Myers Squibb
- Bristol-Myers Squibb, Merck, and Regado Biosciences
- Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, and Daiichi Sankyo
- Sanofi-Aventis, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer, and Daiichi Sankyo
- Servier, Sanofi, and New York University School of Medicine
- AstraZeneca, Merck, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, and GlaxoSmithKline
- Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic Foundation, Merck & Co, Pfizer, Sanofi-Aventis, Takeda, and The Medicines Company
- 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 › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- apixaban, warfarin, atrial fibrillation, major bleeding, intracranial hemorrhage, extracranial hemorrhage, 30-day mortality, bleeding risk factors, oral anticoagulants, ARISTOTLE trial, stroke prevention
- MeSH terms
- Aged, Anticoagulants, Atrial Fibrillation, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Hemorrhage, Humans, Male, Middle Aged, Prognosis, Pyrazoles, Pyridones, Retrospective Studies, Thromboembolism, Warfarin, Global Health, Incidence, Survival Rate, Stroke
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