Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial
Abstract
BACKGROUND: The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial showed that dabigatran etexilate 150 mg BID was superior and dabigatran etexilate 110 mg BID was noninferior to warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation. In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and did not receive concomitant antiplatelets. METHODS AND RESULTS: All comparisons used a Cox proportional hazards model with adjustments made for risk factors for bleeding. A time-dependent analysis was performed when comparing patients with concomitant antiplatelets with those without. Of 18 113 patients, 6952 (38.4%) received concomitant aspirin or clopidogrel at some time during the study. Dabigatran etexilate 110 mg BID was noninferior to warfarin in reducing stroke and systemic embolism, whether patients received antiplatelets (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.70-1.25) or not (HR, 0.87; 95% CI, 0.66-1.15; interaction P=0.738). There were fewer major bleeds than warfarin in both subgroups (HR, 0.82; 95% CI, 0.67-1.00 for patients who used antiplatelets; HR, 0.79; 95% CI, 0.64-0.96 for patients who did not; interaction P=0.794). Dabigatran etexilate 150 mg BID reduced the primary outcome of stroke and systemic embolism in comparison with warfarin. This effect seemed attenuated among patients who used antiplatelets (HR, 0.80; 95% CI, 0.59-1.08) in comparison with those who did not (HR, 0.52; 95% CI, 0.38-0.72; P for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR, 0.93; 95% CI, 0.76-1.12 for patients who used antiplatelets; HR, 0.94; 95% CI, 0.78-1.15 for patients who did not; P for interaction=0.875). In the time-dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR, 1.60; 95% CI, 1.42-1.82). Dual antiplatelet seemed to increased this even more (HR, 2.31; 95% CI, 1.79-2.98). The absolute risks were lowest on dabigatran etexilate 110 mg BID in comparison with dabigatran etexilate 150 mg BID or warfarin. CONCLUSIONS: Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between dabigatran etexilate 110 mg BID and dabigatran etexilate 150 mg BID requires a careful assessment of characteristics that influence the balance between benefit and harm. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00262600.
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Co-prescription of OAC with antiplatelet therapy, in particular triple therapy, increases the absolute risk of major haemorrhage.
“Co-prescription of OAC with antiplatelet therapy, in particular triple therapy, 1501 increases the absolute risk of major haemorrhage.445,517,518”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [445]
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- Authors
- Dans, A. L., Connolly, S. J., Wallentin, L., Yang, S., Nakamya, J., Brueckmann, M., Ezekowitz, M., Oldgren, J., Eikelboom, J. W., Reilly, P. A., & Yusuf, S.
- Affiliations
- Uppsala University (SE)
- ORCID
- Venue
- Circulation
- Published
- 2013-02-05
- Volume
- 127
- Issue
- 5
- Pages
- 634-640
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2165626532
- Cited by
- 484
- References
- 15
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 19 · 2021: 27 · 2020: 32 · 2019: 39 · 2018: 61 · 2017: 52 · 2016: 63 · 2015: 62 · 2014: 49 · 2013: 48 · 2012: 8
- FWCI
- 33.94
- Type
- journal article
- Language
- en
- Update notices
- correction (2013-04-09)
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- 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 › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- dabigatran, warfarin, antiplatelet therapy, aspirin, clopidogrel, atrial fibrillation, stroke and systemic embolism, major bleeding, RE-LY trial, direct oral anticoagulants, drug interactions, non-inferiority, bleeding risk stratification, time-dependent analysis, subgroup analysis, anticoagulant efficacy and safety
- MeSH terms
- Dabigatran, Aged, Aged, 80 and over, Anticoagulants, Atrial Fibrillation, Benzimidazoles, Dose-Response Relationship, Drug, Drug Therapy, Combination, Embolism, Female, Hemorrhage, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Pyridines, Risk Factors, Time Factors, Warfarin, Treatment Outcome, Risk Assessment, Stroke
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