A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke

Background: Despite the use of antiplatelet agents, usually aspirin, in pat ients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effectiv e and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patie nts 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 normaliz ed ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combine d primary end point of recurrent ischemic stroke or death from any cause wi thin 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 diffe rences were found between the treatment groups in any of the outcomes measu red. The primary end point of death or recurrent ischemic stroke was reache d by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 11 03 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfar in with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The r ates of major hemorrhage were low (2.22 per 100 patient-years in the warfar in 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 ti me to the primary end point or major hemorrhage according to the cause of t he initial stroke. Conclusions: Over a two-year period, 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 as pirin as reasonable therapeutic alternatives.