High-dose aspirin is just as effective as warfarin in treating intracranial arterial stenosis, and appears much safer, Marc Chimowitz, M.B., and colleagues have reported.
“The common practice of administering warfarin rather than aspirin for symptomatic intracranial arterial stenosis is not supported by the results of this trial,” said Dr. Chimowitz of Emory University, Atlanta.
Enrollment in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial ended early because of the high rate of serious adverse events in the warfarin patients. In addition to being safer for patients, the researchers said, aspirin therapy did not require constant monitoring of international normalized ratios (INRs) and treatment of warfarin-associated bleeding. Aspirin also is much cheaper, they noted (N. Engl. J. Med. 2005;352:1305-16).
Ralph Sacco, M.D., an investigator in the Northern Manhattan Stroke Study, noted in an interview that the WASID trial's findings add to existing data to dispel beliefs about the benefit of warfarin for certain stroke populations.
The conclusion that warfarin provides no survival benefit over aspirin, but confers added risk, is more expensive, and requires intensive monitoring, should reshape its risk/benefit profile for some patients, said Dr. Sacco, professor of neurology and epidemiology at Columbia University, New York.
Dr. Chimowitz and his associates reported on the trial's final analysis that included 569 patients with symptomatic intracranial arterial stenosis who were randomized to either warfarin 5 mg daily or aspirin 650 mg twice daily.
The patients' mean age was about 63 years; about 61% were men. All had a history of either stroke or transient ischemic attack caused by 50%-90% stenosis of a major intracranial artery. The mean follow-up was 1.8 years.
The primary outcome—stroke, brain hemorrhage, or death from vascular causes other than stroke—occurred in 22% (62) of the aspirin patients and 21.8% (63) of the warfarin patients. Myocardial infarction or sudden death occurred significantly more often in the warfarin group than in the aspirin group (7.3% vs. 2.9%).
The overall rate of death was significantly higher in the warfarin group than in the aspirin group: 5.9% (17) vs. 4.3% (12). However, chance probably accounted for some of the deaths that were higher in the warfarin group, especially the six cancers. Major hemorrhages occurred significantly more often in the warfarin group (8.3% vs 3.2%).
Dr. Sacco noted that warfarin is “clearly indicated” for cardioembolic stroke. “This has been made clear in multiple studies, which were actually so positive that they were the springboard for these other studies looking at warfarin in different populations.”