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A Comparison of Warfarin and Aspirin for the Prevention of Recurrent Ischemic Stroke
Open accessAbstract
BACKGROUND: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. METHODS: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. RESULTS: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery). CONCLUSIONS: Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.
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“In such patients oral vitamin K antagonists are not superior to aspirin but are associated with a higher bleeding risk.512,513”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [512]
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“…of aspirin treatment failure stem from post-hoc analyses from 3 major multicenter, double-blind, randomized stroke trials: Warfarin-Aspirin Symptomatic Intracranial Disease (WASID), 27 Warfarin-Aspirin Recurrent Stroke Study Group (WARSS), 28 and Ticlopidine Aspirin Stroke Study Group (TASS).”
Self-citationPotential new uses of non–vitamin K antagonist oral anticoagulants to treat and prevent stroke
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“8 was not superior to aspirin for the prevention of recurrent stroke among patients with noncardioembolic stroke in the Warfarin vs Aspirin Recurrent Stroke Study (WARSS).(15) Among the prespecified subgroup of patients with cryptogenic stroke in WARSS, however, there was some evidence of benefit, with a reduction of…”
BackgroundResultUpdate of secondary stroke prevention
Diener, H., & Weimar, C. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp068 · Cited by 13
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“[7-12] In addition to being a common cause of stroke, ICAS also is associated with a higher risk of recurrent stroke compared with most other cerebrovascular diseases.[17-22]”
BackgroundCombining oral anticoagulation and antiplatelet therapies: appropriate patient selection
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Oral Anticoagulant Therapy for the Prevention of Stroke
Powers, W. J. (2001) · New England Journal of Medicine · doi:10.1056/nejm200111153452012 · Cited by 13
La ausencia de significación estadística en un ensayo clínico no significa equivalencia terapéutica
Argimón, J. M. (2002) · Medicina Clínica · doi:10.1016/s0025-7753(02)72502-5 · Cited by 13
Antiplatelets in Stroke Prevention
Pinto, A. V., Raimondo, D. D., Tuttolomondo, A., Buttà, C., & Licata, G. (2014) · Current Vascular Pharmacology · doi:10.2174/157016111106140128112915 · Cited by 13
“Two subsequent studies, the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) [31], an European trial that compared warfarin with aspirin in patients with TIA or minor stroke during the previous six months, and the Warfarin vs. Aspirin in Recurrent Stroke Prevention Study (WARSS) [32], in which lower doses of wa…”
BackgroundVascular Diseases of the Nervous System
Biller, J., Love, B. B., & Schneck, M. J. (2008) · Elsevier eBooks · doi:10.1016/b978-0-7506-7525-3.50069-8 · Cited by 13
Hertzberg, V., Chimowitz, M. I., Lynn, M., Chester, C., Asbury, W. H., & Cotsonis, G. (2008) · Clinical Trials · doi:10.1177/1740774507087781 · Cited by 13
“In the Warfarin-Aspirin Recurrent Stroke Study (WARSS) [9], all patients were held to the same schedule for clinic visits to draw blood, measure INR levels, and adjust placebo or active warfarin dose.”
MethodAntiplatelets in Stroke Prevention: The MATCH Trial
Bezerra, D. C., & Bogousslavsky, J. (2005) · Cerebrovascular Diseases · doi:10.1159/000089363 · Cited by 12
Update on the treatment and prevention of ischaemic stroke
Alberts, M. J. (2003) · Current Medical Research and Opinion · doi:10.1185/030079903125001956 · Cited by 13
A Benefit-Risk Assessment of Agents Used in the Secondary Prevention of Stroke
MacWalter, R. S., & Shirley, C. P. (2002) · Drug Safety · doi:10.2165/00002018-200225130-00005 · Cited by 13
“8) and aspirin (325 mg/day)[44] in patients with prior non-cardioembolic stroke.”
BackgroundAtrial Cardiopathy: Redefining Stroke Risk Beyond Atrial Fibrillation
Zhang, J., & Bhat, A. (2023) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.06.002 · Cited by 11
Pruissen, D. M. O., Rosendaal, F. R., Gorter, J. W., Garcia, A. A., Kappelle, L. J., Algra, A., & for the SPIRIT Study Group* (2007) · Journal of Neurology · doi:10.1007/s00415-007-0609-5 · Cited by 12
“For patients after cerebral ischaemia of presumed arterial origin a benefit of treatment with oral anticoagulants has not been shown [2, 10, 27, 37].”
BackgroundCardiac Procedures to Prevent Stroke: Patent Foramen Ovale Closure/Left Atrial Appendage Occlusion
Freixa, X., Arzamendi, D., Tzikas, A., Noble, S., Basmadjian, A., Garceau, P., & Ibrahim, R. (2013) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2013.11.008 · Cited by 12
“At 2-year follow-up, no significant differences in stroke recurrence, death, or major bleeding were observed.(19) In a subanalysis of the study comparing aspirin and warfarin in patients with PFO and cryptogenic infarction (Patent Foramen Ovale in Cryptogenic Stroke [PICSS] trial), the stroke rate at 2 years was simil…”
BackgroundMusat, D. L., Milstein, N. S., & Mittal, S. (2018) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2017.11.011 · Cited by 12
Diagnosis and Management of Cardioembolic Stroke
Yaghi, S. R. (2023) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001217 · Cited by 13
Personalized Medicine: the Impact on Chemistry
Watkins, J., Marsh, A., Taylor, P. C., & Singer, D. R. J. (2010) · Therapeutic Delivery · doi:10.4155/tde.10.64 · Cited by 13
Stroke and Patent Foramen Ovale in Young Individuals
Piechowski‐Jóźwiak, B., & Bogousslavsky, J. (2012) · European Neurology · doi:10.1159/000342900 · Cited by 12
Traitement du syndrome des anticorps antiphospholipides
Saadoun, D., Pietté, J. C., Wahl, D. G., & Costedoat-Chalumeau, N. (2012) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2012.01.007 · Cited by 12
Markl, M., Semaan, E., Stromberg, L., Carr, J., Prabhakaran, S., & Collins, J. D. (2017) · European Radiology · doi:10.1007/s00330-017-4821-0 · Cited by 12
Antiplatelet therapy for peripheral artery disease
Melfi, R., & Ricottini, E. (2018) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt.2018.07.02 · Cited by 12
Stroke and Other Neurovascular Disorders
Chung, C., & Caplan, L. R. (2007) · Elsevier eBooks · doi:10.1016/b978-141603618-0.10045-1 · Cited by 13
Metadata
- Authors
- Mohr, J. P., Thompson, J. L. P., Lazar, R. M., Levin, B., Sacco, R. L., Furie, K. L., Kistler, J. P., Albers, G. W., Pettigrew, L. C., Adams, H. P., Jackson, C. M., & Pullicino, P.
- Affiliations
- Columbia University Irving Medical Center (US)
- Massachusetts General Hospital (US)
- Stanford Medicine (US)
- University of Kentucky (US)
- University of California San Diego (US)
- University at Buffalo, State University of New York (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2001-11-15
- Volume
- 345
- Issue
- 20
- Pages
- 1444-1451
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2027538725
- Cited by
- 1,168
- References
- 39
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 13 · 2023: 22 · 2022: 20 · 2021: 40 · 2020: 24 · 2019: 37 · 2018: 32 · 2017: 33 · 2016: 50 · 2015: 41 · 2014: 54 · 2013: 39 · 2012: 49
- FWCI
- 54.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Yale University
- University of Southern California
- Vanderbilt University
- University of Miami
- Wayne State University
- Cleveland Clinic
- Cleveland Clinic Foundation
- Johns Hopkins University
- Hennepin County Medical Center
- University of South Alabama
- York University
- University of Illinois at Urbana-Champaign
- National Institute of Neurological Disorders and Stroke (R01NS028371)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- warfarin, aspirin, recurrent ischemic stroke, secondary stroke prevention, antiplatelet therapy, major bleeding, non-cardioembolic stroke, lacunar infarction, cryptogenic stroke, international normalized ratio, anticoagulation
- MeSH terms
- Adult, Aged, Aged, 80 and over, Anticoagulants, Aspirin, Brain Ischemia, Double-Blind Method, Female, Hemorrhage, Humans, Male, Middle Aged, Mortality, Platelet Aggregation Inhibitors, Risk Factors, Warfarin, International Normalized Ratio, Stroke, Secondary Prevention
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