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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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Atrial Septal Aneurysm may Cause In-Hospital Recurrence of Cryptogenic Stroke
Kuriki, A., Ueno, Y., Kamiya, Y., Shimizu, T., Doijiri, R., Tateishi, Y., Kikuno, M., Shimada, Y., Takekawa, H., Yamaguchi, E., et al. (2020) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.56440 · Cited by 9
Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation
Witte, K. K., Tsivgoulis, G. K., Reynolds, M. R., Tsintzos, S. I., Eggington, S., Ismyrloglou, E., Lyon, J., Huynh, M., Egea, M., de Brouwer, B., et al. (2021) · BMC Cardiovascular Disorders · doi:10.1186/s12872-021-01967-x · Cited by 8
Toi, S., Shirai, Y., Ishizuka, K., Hosoya, M., Seki, M., Higuchi, E., Hoshino, T., & Kitagawa, K. (2021) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.61895 · Cited by 9
Current Indications for Percutaneous Closure of Patent Foramen Ovale
Hernández‐Enríquez, M., & Freixa, X. (2014) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2014.01.008 · Cited by 8
Garg, P., & Walton, A. (2008) · Heart Lung and Circulation · doi:10.1016/j.hlc.2007.10.019 · Cited by 8
Patent foramen ovale and its relationship to stroke
Cramer, S. C. (2005) · Cardiology Clinics · doi:10.1016/j.ccl.2004.10.006 · Cited by 8
“8% [6], although a substudy found that the annual rate of death/recurrent stroke after a cryptogenic stroke was not significantly different when PFO was present (7.”
BackgroundPatent Foramen Ovale and Stroke: Prognosis and Treatment in Young Adults
Cramer, S. C. (2005) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-005-3202-8 · Cited by 8
“8% [9], though a substudy found that the annual rate of death/recurrent stroke after a cryptogenic stroke was not significantly different when PFO was (7.”
S3-Leitlinie Extracranielle Carotisstenose
Berkefeld, J., & Dörfler, A. (2012) · Gefässchirurgie · doi:10.1007/s00772-012-1057-9 · Cited by 8
Diagnosis and management of patent foramen ovale
Ghosh, A. K., & Jain, A. (2015) · British Journal of Hospital Medicine · doi:10.12968/hmed.2015.76.7.c98 · Cited by 8
McClure, L. A., Szychowski, J. M., Benavente, O., Hart, R. G., & Coffey, C. S. (2016) · Clinical Trials · doi:10.1177/1740774516643689 · Cited by 8
Antithrombotic and Thrombolytic Therapy for Ischemic Stroke
Ocava, L., Singh, M., Malhotra, S., & Rosenbaum, D. M. (2006) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2005.09.006 · Cited by 8
Importance of Performing Transesophageal Echocardiography in Acute Stroke Patients older than Fifty
Gupta, N., Lau, C., Al‐Dehneh, A., Daoko, J., Vazir, A., Parikh, R. R., Agarwal, A., Newton, W., Dhillon, W. S., Gupta, I., et al. (2010) · Echocardiography · doi:10.1111/j.1540-8175.2010.01203.x · Cited by 8
Stroke in Older Survivors of Ischemic Stroke: Standard Care or Something Different?
Hubbard, I. J., Wass, S., & Pepper, E. (2017) · Geriatrics · doi:10.3390/geriatrics2020018 · Cited by 9
“Anticoagulant therapy is not recommended in those with non-cardioembolic ischemic stroke due to the increased risk of bleeding, based on the results of the WARS Study [42,43].”
BackgroundControversies in the antiphospholipid syndrome and stroke
Gatenby, P. A. (2004) · Thrombosis Research · doi:10.1016/j.thromres.2004.06.033 · Cited by 8
Anticoagulation for secondary stroke prevention: another nail in the coffin?
Elkind, M. S. V. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70008-x · Cited by 8
Cuadrado, M. J. (2002) · Current Rheumatology Reports · doi:10.1007/s11926-002-0083-0 · Cited by 8
“A recent multicenter, double blind, randomized trial [ 27 ] compared the efficacy and safety of aspirin (325 mg per day) versus oral anticoagulation (INR = 1.4–2.8).”
BackgroundInfluentialPrognostic factors and therapeutic outcome of isolated symptomatic middle cerebral artery stenosis
Tsai, N., Chang, H. ‐., Chang, W. ‐., Huang, C., Lin, T. ‐., Chen, S., Lui, C., Wang, K., Cheng, B. ‐., Hung, P., et al. (2005) · European Journal of Neurology · doi:10.1111/j.1468-1331.2005.00995.x · Cited by 8
Antiplatelet Agents and Arterial Thrombosis
Billett, H. H. (2008) · Cardiology Clinics · doi:10.1016/j.ccl.2007.12.007 · Cited by 8
Thoughts Evoked by MATCH and Other Trials
Caplan, L. R. (2004) · Stroke · doi:10.1161/01.str.0000145197.94684.48 · Cited by 8
Anti-β2-Glycoprotein I Antibodies and Ischemic Stroke in a 20-Month-Old Boy
Katsarou, E., Attilakos, A., Fessatou, S., Tsapra, H., Tzavara, V., & Dracou, C. (2003) · PEDIATRICS · doi:10.1542/peds.112.1.188 · Cited by 8
Anticoagulation and platelet antiaggregation therapy in stroke prevention
Chong, J. Y., & Mohr, J. P. (2005) · Current Opinion in Neurology · doi:10.1097/00019052-200502000-00011 · Cited by 8
Self-citation
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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