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Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation: An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial
Open accessAbstract
BACKGROUND: Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. METHODS AND RESULTS: The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged <75 years (1.89% versus 3.04%; P<0.001) and a similar risk in those aged ≥75 years (4.43% versus 4.37%; P=0.89; P for interaction <0.001), whereas dabigatran 150 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in those aged <75 years (2.12% versus 3.04%; P<0.001) and a trend toward higher risk of major bleeding in those aged ≥75 years (5.10% versus 4.37%; P=0.07; P for interaction <0.001). The interaction with age was evident for extracranial bleeding, but not for intracranial bleeding, with the risk of the latter being consistently reduced with dabigatran compared with warfarin irrespective of age. CONCLUSIONS: In patients with atrial fibrillation at risk for stroke, both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients aged <75 years. In those aged ≥75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
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“The risk of gastrointestinal bleeds was comparable to warfarin on dabigatran 110 mg twice daily 490 and on apixaban 5 mg twice daily 319”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [490]
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“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 [490]
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“Относительный риск развития кровотечений в группе, принимающей дозировку 110 мг 2 раза в сутки, оказался ниже в сравнении с группой, принимающей дозировку 150Oмг 2 раза в сутки, и составлял 0,87 для больших и 0,88 для малых кровотечений [5, 19].”
Enokiya, T., Hasegawa, M., Morikawa, Y., Muraki, Y., Sudo, A., & Okuda, M. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00447 · Cited by 6
Николаевич, Б. С., Егорова, Ю. В., & Платонов, Д. Ю. (2019) · Medicina · doi:10.29234/2308-9113-2019-7-4-1-11 · Cited by 6
Rubino, C., Blunda, F., Bodega, F., Melillo, F., Russi, A., Mattiello, P., Salerno, A., Cera, M., Margonato, D., Mazzone, P., et al. (2022) · Minerva Medica · doi:10.23736/s0026-4806.21.07432-2 · Cited by 6
Rolden, H. J. A., Grutters, J. P. C., van der Wilt, G. J., & Maas, A. H. E. M. (2015) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvv020 · Cited by 6
Arches, C., Eddine, A. J., Beauport, D. T., Dao, M., Lobbedez, T., Zaoui, P., Masset, C., Bertrand, D., Karoui, K. E., Brenier, H., et al. (2025) · Kidney International Reports · doi:10.1016/j.ekir.2025.01.042 · Cited by 5
“36,37 In our cohort, being female and aged > 75 years were risk factors associated with bleeding events in univariate analysis.”
Stroke Prevention With Oral Anticoagulants in High-Risk Atrial Fibrillation in an Aging Population
Okumura, K., Akao, M., Suzuki, S. S., & Yamashita, T. (2025) · JACC Advances · doi:10.1016/j.jacadv.2025.101757 · Cited by 6
Chou, T., Lin, Y., Tsai, M., Tseng, C.-J., Dai, J.-W., Yang, N., Lin, C., Chen, L., Hung, M., & Chen, T. (2024) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000002089 · Cited by 6
Drapkina, O. M., Boytsov, S. A., Golukhova, E. Z., Davtyan, K. V., Drozdova, L. Y., Ipatov, P. V., Калинина, А. М., Martsevich, S. Y., Savchenko, E. D., Kharlap, M. S., et al. (2024) · Primary Health Care (Russian Federation) · doi:10.15829/3034-4123-2024-24 · Cited by 6
Mo, G.-L., Wen, J. A., Ye, Y.-Y., Lu, Y., Gan, T.-M., Yang, Y., & Li, J.-Y. (2025) · Reviews in Cardiovascular Medicine · doi:10.31083/rcm26055 · Cited by 5
Liu, G. J., Wang, Y. F., Chen, P. Y., Chang, W., Tu, M. L., Chang, L. Y., Cheng, P., & Luo, J. (2014) · Drug Delivery · doi:10.3109/10717544.2013.873500 · Cited by 5
“It is worth mentioning that the large-dose regimen of novel oral anticoagulants achieved a higher level of efficacy but a greatly lower level of safety than the small- dose regimen, which is in agreement with a report of the RE-LY trial (Eikelboom et al., 2011).”
ResultTarget specific oral anticoagulants in the management of thromboembolic disease in the elderly
Maddula, S., & Ansell, J. (2013) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-013-0926-8 · Cited by 5
Management of risk factors for gastrointestinal bleeding in patients receiving anticoagulant therapy
Бакулина, Н. В., Викторович, Т. С., Лищук, Н. Б., & Karaya, A. B. (2021) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2021-4635 · Cited by 5
Álvarez, F. C., Martínez, A. A., Silero, P. L., Orive, A., Redondo‐Cerezo, E., de Santiago, E. R., & García, J. C. (2022) · Revista Española de Enfermedades Digestivas · doi:10.17235/reed.2022.8920/2022 · Cited by 5
Stefano, F. D., Benassi, A., Cappelletti, A. M., Donatelli, F., Regazzoli, D., Tolaro, S., Perego, F., Silverio, A., Scatteia, A., Guarini, P., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091419 · Cited by 5
Rus, M., Ardelean, A. I., Crișan, S., Marian, P., Pobirci, O. L., Huplea, V., Pusta, C. T. J., Osiceanu, A. G., Staniș, C. E., & Andronie-Cioară, F. L. (2024) · Clinics and Practice · doi:10.3390/clinpract14010027 · Cited by 5
A small-molecule hemostatic agent for the reversal of direct oral anticoagulant–induced bleeding
Desvages, M., Borgel, D., Adam, F., Tu, G., Jaouen, S., Repérant, C., Denis, C. V., Desmaële, D., & Bianchini, E. P. (2024) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2024.102426 · Cited by 5
“However, some DOACs increase the risk of gastrointestinal hemorrhage [3 – 6].”
BackgroundCatheter-based Epicardial Closure of the Left Atrial Appendage
Santoro, F., Biase, L. D., Santangeli, P., Bai, R., Danik, S. B., Barrett, C. D., Horton, R., Burkhardt, J. D., & Natale, A. (2014) · Interventional Cardiology Clinics · doi:10.1016/j.iccl.2014.01.003 · Cited by 5
Metadata
- Authors
- Eikelboom, J. W., Wallentin, L., Connolly, S. J., Ezekowitz, M., Healey, J. S., Oldgren, J., Yang, S., Alings, M., Kaatz, S., Hohnloser, S. H., Diener, H.-C., Franzosi, M. G., Huber, K., Reilly, P., Varrone, J., & Yusuf, S.
- Affiliations
- Goethe University Frankfurt (DE)
- ORCID
- Venue
- Circulation
- Published
- 2011-05-31
- Volume
- 123
- Issue
- 21
- Pages
- 2363-2372
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2064357176
- Cited by
- 1,081
- References
- 16
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 21 · 2023: 20 · 2022: 36 · 2021: 43 · 2020: 64 · 2019: 61 · 2018: 56 · 2017: 77 · 2016: 95 · 2015: 121 · 2014: 99 · 2013: 167 · 2012: 156
- FWCI
- 100.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- 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 › Clinical Neurology › Acute Ischemic Stroke Management
- Keywords
- dabigatran, warfarin, atrial fibrillation, major bleeding, intracranial hemorrhage, extracranial hemorrhage, stroke prevention, anticoagulation, elderly patients, age interaction, RE-LY trial, direct thrombin inhibitors, dose comparison, international normalized ratio, bleeding risk stratification, bleeding risk prediction model
- MeSH terms
- Dabigatran, Age Factors, Aged, Aged, 80 and over, Anticoagulants, Atrial Fibrillation, Benzimidazoles, Drug Administration Schedule, Female, Hemorrhage, Humans, Male, Middle Aged, Risk Factors, Time Factors, Warfarin, beta-Alanine
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