Cited by 1,168Acute Ischemic Stroke ManagementAntiplatelet Therapy and Cardiovascular DiseasesAtrial Fibrillation Management and Outcomes

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A Comparison of Warfarin and Aspirin for the Prevention of Recurrent Ischemic Stroke

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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.·2001·New England Journal of Medicine

DOI 10.1056/nejmoa011258

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Abstract

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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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: Mohr, J.P.
Thompson, J.L.P.
Lazar, R.M.
Sacco, R.L.
Furie, K.L.
Albers, G.W.
Pettigrew, L.C.
Adams, H.P.
Pullicino, P.
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
DOI: 10.1056/nejmoa011258
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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A Comparison of Warfarin and Aspirin for the Prevention of Recurrent Ischemic Stroke

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