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Background: Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy., Methods and Results: WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis > or =70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in patients enrolled early (< or =17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk., Conclusions: Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis > or =70%, after recent symptoms, and in women.

Background: Atherosclerotic intracranial arterial stenosis is an important cause of stroke. Warfarin is commonly used in preference to aspirin for this disorder, but these therapies have not been compared in a randomized trial., Methods: We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent 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, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin. During a mean follow-up period of 1.8 years, adverse events in the two groups included death (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin 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 to 0.84; P=0.01), and myocardial infarction or sudden death (2.9 percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.02). The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group (P=0.16); the rate of death from nonvascular causes was 1.1 percent and 3.8 percent, respectively (P=0.05). The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group (hazard ratio, 1.04; 95 percent confidence interval, 0.73 to 1.48; P=0.83)., Conclusions: Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial. Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis., (Copyright 2005 Massachusetts Medical Society.)