March 31, 2005

http://content.nejm.org/cgi/content/short/352/13/1305

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

ABSTRACT

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.