Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis
Marc I. Chimowitz, M.B., Ch.B., Michael J. Lynn, M.S., Harriet Howlett-Smith, R.N., Barney J. Stern, M.D., Vicki S. Hertzberg, Ph.D., Michael R. Frankel, M.D., Steven R. Levine, M.D., Seemant Chaturvedi, M.D., Scott E. Kasner, M.D., Curtis G. Benesch, M.D., Cathy A. Sila, M.D., Tudor G. Jovin, M.D., Jose G. Romano, M.D., for the Warfarin–Aspirin Symptomatic Intracranial Disease Trial Investigators
Background Atherosclerotic intracranial arterial stenosis isan important cause of stroke. Warfarin is commonly used in preferenceto aspirin for this disorder, but these therapies have not beencompared in a randomized trial.
Methods We randomly assigned patients with transient ischemicattack or stroke caused by angiographically verified 50 to 99percent stenosis of a major intracranial artery to receive warfarin(target international normalized ratio, 2.0 to 3.0) or aspirin(1300 mg per day) in a double-blind, multicenter clinical trial.The primary end point was ischemic stroke, brain hemorrhage,or death from vascular causes other than stroke.
Results After 569 patients had undergone randomization, enrollmentwas stopped because of concerns about the safety of the patientswho had been assigned to receive warfarin. During a mean follow-upperiod of 1.8 years, adverse events in the two groups includeddeath (4.3 percent in the aspirin group vs. 9.7 percent in thewarfarin group; hazard ratio for aspirin relative to warfarin,0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02),major hemorrhage (3.2 percent vs. 8.3 percent, respectively;hazard ratio, 0.39; 95 percent confidence interval, 0.18 to0.84; P=0.01), and myocardial infarction or sudden death (2.9percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95percent confidence interval, 0.18 to 0.91; P=0.02). The rateof death from vascular causes was 3.2 percent in the aspiringroup and 5.9 percent in the warfarin group (P=0.16); the rateof death from nonvascular causes was 1.1 percent and 3.8 percent,respectively (P=0.05). The primary end point occurred in 22.1percent of the patients in the aspirin group and 21.8 percentof those in the warfarin group (hazard ratio, 1.04; 95 percentconfidence interval, 0.73 to 1.48; P=0.83).
Conclusions Warfarin was associated with significantly higherrates of adverse events and provided no benefit over aspirinin this trial. Aspirin should be used in preference to warfarinfor patients with intracranial arterial stenosis.
Source Information
From the Department of Neurology, School of Medicine (M.I.C., H.H.-S., B.J.S., M.R.F.), and the Department of Biostatistics, Rollins School of Public Health (M.J.L., V.S.H.), Emory University, Atlanta; the Department of Neurology, Mount Sinai School of Medicine, New York (S.R.L.); the Department of Neurology, Wayne State University, Detroit (S.C.); the Department of Neurology, University of Pennsylvania School of Medicine (S.E.K.); the Department of Neurology, University of Rochester School of Medicine, Rochester, N.Y. (C.G.B.); the Department of Neurology, Cleveland Clinic Foundation, Cleveland (C.A.S.); the Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh (T.G.J.); and the Department of Neurology, University of Miami Medical School, Miami (J.G.R.).
Address reprint requests to Dr. Chimowitz at the Department of Neurology, Emory Clinic, 4th Fl., Clinic A Bldg., 1365 Clifton Rd., Atlanta, GA 30322, or at mchimow{at}emory.edu.
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67: 1184-1188
[Abstract][Full Text]
Kasner, S. E., Lynn, M. J., Chimowitz, M. I., Frankel, M. R., Howlett-Smith, H., Hertzberg, V. S., Chaturvedi, S., Levine, S. R., Stern, B. J., Benesch, C. G., Jovin, T. G., Sila, C. A., Romano, J. G., for the Warfarin Aspirin Symptomatic Intracranial,
(2006). Warfarin vs aspirin for symptomatic intracranial stenosis: Subgroup analyses from WASID.. Neurology
67: 1275-1278
[Abstract][Full Text]
Wojak, J.C., Dunlap, D.C., Hargrave, K.R., DeAlvare, L.A., Culbertson, H.S., Connors, J.J. III
(2006). Intracranial angioplasty and stenting: long-term results from a single center.. Am. J. Neuroradiol.
27: 1882-1892
[Abstract][Full Text]
Gupta, R., Al-Ali, F., Thomas, A. J., Horowitz, M. B., Barrow, T., Vora, N. A., Uchino, K., Hammer, M. D., Wechsler, L. R., Jovin, T. G.
(2006). Safety, Feasibility, and Short-Term Follow-Up of Drug-Eluting Stent Placement in the Intracranial and Extracranial Circulation. Stroke
37: 2562-2566
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Weimar, C., Goertler, M., Harms, L., Diener, H.-C., for the German Stroke Study Collaboration,
(2006). Distribution and outcome of symptomatic stenoses and occlusions in patients with acute cerebral ischemia.. Arch Neurol
63: 1287-1291
[Abstract][Full Text]
Meyers, P. M., Phatouros, C. C., Higashida, R. T.
(2006). Hyperperfusion Syndrome After Intracranial Angioplasty and Stent Placement. Stroke
37: 2210-2211
[Full Text]
Marder, V. J., Chute, D. J., Starkman, S., Abolian, A. M., Kidwell, C., Liebeskind, D., Ovbiagele, B., Vinuela, F., Duckwiler, G., Jahan, R., Vespa, P. M., Selco, S., Rajajee, V., Kim, D., Sanossian, N., Saver, J. L.
(2006). Analysis of Thrombi Retrieved From Cerebral Arteries of Patients With Acute Ischemic Stroke. Stroke
37: 2086-2093
[Abstract][Full Text]
Levy, E. I., Chaturvedi, S.
(2006). Perforator stroke following intracranial stenting: A sacrifice for the greater good?. Neurology
66: 1803-1804
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Ovbiagele, B., Saver, J. L., Lynn, M. J., Chimowitz, M., for the WASID Study Group,
(2006). Impact of metabolic syndrome on prognosis of symptomatic intracranial atherostenosis. Neurology
66: 1344-1349
[Abstract][Full Text]
Mazighi, M., Tanasescu, R., Ducrocq, X., Vicaut, E., Bracard, S., Houdart, E., Woimant, F.
(2006). Prospective study of symptomatic atherothrombotic intracranial stenoses: The GESICA Study. Neurology
66: 1187-1191
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Marks, M. P., Wojak, J. C., Al-Ali, F., Jayaraman, M., Marcellus, M. L., Connors, J. J., Do, H. M.
(2006). Angioplasty for Symptomatic Intracranial Stenosis: Clinical Outcome. Stroke
37: 1016-1020
[Abstract][Full Text]
Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T.
(2006). Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.. Circulation
113: e409-e449
[Abstract][Full Text]
Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T.
(2006). Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.. Stroke
37: 577-617
[Abstract][Full Text]
Kasner, S. E., Chimowitz, M. I., Lynn, M. J., Howlett-Smith, H., Stern, B. J., Hertzberg, V. S., Frankel, M. R., Levine, S. R., Chaturvedi, S., Benesch, C. G., Sila, C. A., Jovin, T. G., Romano, J. G., Cloft, H. J., for the Warfarin Aspirin Symptomatic Intracranial,
(2006). Predictors of Ischemic Stroke in the Territory of a Symptomatic Intracranial Arterial Stenosis. Circulation
113: 555-563
[Abstract][Full Text]
Michel, P, Bogousslavsky, J
(2006). Shared mechanisms of ischaemic and haemorrhagic stroke: still a lot to learn. J. Neurol. Neurosurg. Psychiatry
77: 1-1
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Touze, E., Varenne, O., Chatellier, G., Peyrard, S., Rothwell, P. M., Mas, J.-L.
(2005). Risk of Myocardial Infarction and Vascular Death After Transient Ischemic Attack and Ischemic Stroke: A Systematic Review and Meta-Analysis. Stroke
36: 2748-2755
[Abstract][Full Text]
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