The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Edoxaban versus Warfarin in Patients with Atrial Fibrillation
Open accessAbstract
BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).
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“Edoxaban 60 mg once daily was non-inferior to warfarin (primary outcome, HR 0.87; 97.5% CI 0.73-1.04;P = 0.08).”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [321]
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“while edoxaban 30 mg once daily was non-inferior to warfarin for prevention of stroke and systemic embolism but significantly reduced major bleeding events by 53%.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [321]
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“In an on-treatment analysis, edoxaban 60 mg once daily significantly reduced stroke or systemic embolism by 21% and significantly reduced major bleeding events by 20% compared with warfarin”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [321]
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“Renal clearance”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [321]
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Dabigatran versus warfarin in patients with atrial fibrillation
Connolly, S. J., Ezekowitz, M. D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., Pogue, J., Reilly, P. A., Themeles, E., Varrone, J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0905561 · Cited by 11,215
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation
Patel, M. R., Mahaffey, K. W., Garg, J., Pan, G., Singer, D. E., Hacke, W., Breithardt, G., Halperin, J. L., Hankey, G. J., Piccini, J. P., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1009638 · Cited by 9,430
Self-citationApixaban versus warfarin in patients with atrial fibrillation
Granger, C. B., Alexander, J. H., McMurray, J. J. V., Lopes, R. D., Hylek, E. M., Hanna, M., Al-Khalidi, H. R., Ansell, J., Atar, D., Avezum, A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107039 · Cited by 8,943
Schulman, S., & Kearon, C. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01204.x · Cited by 5,025
Gage, B. F., Waterman, A. D., Shannon, W., Boechler, M., Rich, M. W., & Radford, M. J. (2001) · JAMA · doi:10.1001/jama.285.22.2864 · Cited by 4,832
Hart, R. G., Pearce, L. A., & Aguilar, M. I. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-12-200706190-00007 · Cited by 4,793
Schulman, S., Angerås, U., Bergqvist, D., ERIKSSON, B., Lassen, M. R., & FISHER, W. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03678.x · Cited by 3,761
A Method to Determine the Optimal Intensity of Oral Anticoagulant Therapy
Rosendaal, F. R., Cannegieter, S. C., van der Meer, F. J. M., & Briët, E. (1993) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1651587 · Cited by 2,070
The prevention and treatment of missing data in clinical trials
Little, R. J., D'Agostino, R., Cohen, M. L., Dickersin, K., Emerson, S. S., Farrar, J. T., Frangakis, C., Hogan, J. W., Molenberghs, G., Murphy, S. A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmsr1203730 · Cited by 1,884
Self-citationEdoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism
The Hokusai-VTE Investigators (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1306638 · Cited by 1,869
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“9%.(84,86,89,154) Patients with DM were on average 0.”
BackgroundSmall, A. M., Yang, T.-Y., Itoh, S., Thériault, S., Dufresne, L., Kurosawa, R., Komuro, I., Matsuda, K., Vy, H. M. T., Farber-Eger, E. H., et al. (2026) · Nature Genetics · doi:10.1038/s41588-025-02417-6 · Cited by 18
Self-citationAnti-thrombotic therapy in patients with atrial fibrillation and intracranial hemorrhage
Diener, H.-C., Stanford, S., Abdul-Rahim, A., Christensen, L., Hougaard, K. D., Bakhai, A., Veltkamp, R., & Worthmann, H. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.945435 · Cited by 12
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Millar, C. M., & Laffan, M. A. (2017) · Clinical Medicine · doi:10.7861/clinmedicine.17-3-233 · Cited by 11
Kumbhani, D. J., Armbruster, A. L., Cheng, R. K., Chrispin, J., Fischer, U., Holbrook, A. M., Joglar, J., & Sevestre, M.-A. (2026) · JACC · doi:10.1016/j.jacc.2026.05.033 · Cited by 2
Metadata
- Authors
- Giugliano, R. P., Ruff, C. T., Braunwald, E., Murphy, S. A., Wiviott, S. D., Halperin, J. L., Waldo, A. L., Ezekowitz, M. D., Weitz, J. I., Špinar, J., Ruzyllo, W., Ruda, M., Koretsune, Y., Betcher, J., Shi, M., Grip, L. T., Patel, S. P., Patel, I., Hanyok, J. J., Mercuri, M., & Antman, E. M.
- Affiliations
- Brigham and Women's Hospital (US)
- University Hospitals Cleveland Medical Center (US)
- McMaster University (CA)
- National Medical Research Center of Cardiology (RU)
- Osaka National Hospital (JP)
- IQVIA (United States) (US)
- Daiichi Sankyo (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-11-28
- Volume
- 369
- Issue
- 22
- Pages
- 2093-2104
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2096246254
- Cited by
- 5,164
- References
- 24
- Citations by year
- 2026: 201 · 2025: 280 · 2024: 344 · 2023: 419 · 2022: 405 · 2021: 469 · 2020: 505 · 2019: 443 · 2018: 487 · 2017: 454 · 2016: 494 · 2015: 378 · 2014: 266 · 2013: 12
- FWCI
- 260.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Gilead Sciences
- AtriCure
- Boston Scientific Corporation
- Medicines Company
- Janssen Scientific Affairs
- Bayer HealthCare
- Eisai
- St. Jude Medical
- Biosense Webster
- Janssen Pharmaceuticals
- Daiichi Sankyo Europe
- 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
- edoxaban, warfarin, atrial fibrillation, direct oral anticoagulants, factor Xa inhibitors, stroke and systemic embolism, major bleeding, non-inferiority, oral anticoagulation, time in therapeutic range, anticoagulant efficacy and safety, once-daily dosing
- MeSH terms
- Adult, Aged, Anticoagulants, Atrial Fibrillation, Cardiovascular Diseases, Double-Blind Method, Embolism, Female, Follow-Up Studies, Hemorrhage, Humans, Male, Middle Aged, Pyridines, Thiazoles, Warfarin, Stroke, Kaplan-Meier Estimate
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