While use of warfarin for prevention of stroke in patients with atrial fibrillation has become more widely accepted, its role has not been as clear in the much larger group of stroke patients who do not have atrial fibrillation or other embolic risk sources. A previous trial of warfarin anticoagulation for stroke prevention, in which the target International Normalized Ratio (INR) was 3.0 to 4.5, was stopped early when it showed higher rates of major hemorrhage.

Mohr and associates describe a large trial comparing aspirin with warfarin anticoagulation, with a lower INR target of 1.4 to 2.8. In a double-blind, randomized trial, 2,206 patients with nonembolic stroke were assigned to receive aspirin in a dosage of 325 mg once daily, or warfarin. To best preserve blinding, patients randomized to aspirin had fake INR values reported that were adjusted as needed. Patients were followed for two years, comparing rates of recurrent stroke, death from any cause, and bleeding complications. Fewer than 2 percent of study participants in both groups were lost to follow-up.

Recurrent stroke or death occurred in 17.8 percent of patients taking warfarin versus 16.0 percent of those taking aspirin, a difference that was not statistically significant. In addition, there were no differences in subgroups based on gender, race, or cause of previous stroke. Minor bleeding was more common with warfarin than with aspirin (20.8 vs. 12.9 percent), but major bleeding rates were low and similar (2.2 vs. 1.5 percent).

The authors conclude that warfarin anticoagulation with a target INR of 1.4 to 2.8 provided no advantage over aspirin in preventing recurrent stroke.

editor's note: Many medical journals are biased toward the reporting of positive results (i.e., treatment X is better than treatment Y, or treatment Z is deadly for these reasons). Negative results (i.e., no difference) seldom receive much press attention, yet are just as important in making rational clinical decisions. While this study is not likely to make headlines, the findings are no less relevant to any patient or physician trying to make an informed decision about medications for recurrent stroke prevention.—b.z.