Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis

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 >= 70% ( hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P = 0.0025) and in patients enrolled early ( <= 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 >= 70%, after recent symptoms, and in women.