New England Journal of Medicine
Patients at risk of developing a stroke caused by narrowed brain arteries should take aspirin rather than a well-known anti-clotting medication to prevent a stroke from occurring, according to the results of a major national study published in the New England Journal of Medicine on March 31, 2005.
Seemant Chaturvedi, M.D., Wayne State University associate professor of neurology and director of the university's stroke program, conducted the Detroit-area portion of the study and served on the study's steering committee. The research was led by Dr. Marc Chimowitz of Emory University.
Funded by the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health, the nearly $15 million, five-year study ended early because the anti-clotting drug, warfarin (marketed under the brand name Coumadin ), was associated with more complications while showing no advantages over a high dose of aspirin. The study is known as the Warfarin-Aspirin Symptomatic Intracranial Disease study, or WASID.
Doctors describe narrowed or clogged arteries in the brain as intracranial arterial stenosis, accounting for approximately 90,000 strokes or stroke warning spells (transient ischemic attacks or TIAs) per year in the United States. Patients with this condition are at high risk for another stroke.
Warfarin or similar drugs were first suggested as a treatment for stroke caused by narrowed brain arteries 50 years ago. Previous studies had suggested that warfarin may be superior to aspirin for this cause of stroke, but this finding was inconclusive because of the limitations in the design of those studies.
The WASID study was conducted in a double-blind fashion, meaning that neither participants nor researchers knew which medication (warfarin or aspirin) was being taken until the study ended. Participants took either dose-adjusted warfarin (according to monthly blood tests) or 1300 mg. of aspirin daily (a higher dose than is usually recommended for heart disease and strokes of other causes).
The higher dose of aspirin was chosen because this was the dose for which there was the most reliable data from previous studies. There is some evidence that higher doses of aspirin may be more effective for inhibiting inflammation of blood vessels and preventing platelets (blood cells important for clotting) from sticking to the narrowed artery, although this is controversial. The concern with using higher doses of aspirin is the risk of causing stomach ulcers and bleeding from the gastrointestinal tract.
When the WASID study started in February of 1999, researchers had planned to enroll more than 800 participants over five years at more than 50 sites in the U.S. and Canada. However, after 569 participants were enrolled, NINDS stopped the study early on the recommendation of the independent Data Monitoring Committee because the warfarin group was developing complications at a higher rate than the aspirin group.
Complications included higher rates of major bleeding (8.3 percent of warfarin participants vs. 3.2 percent of aspirin participants) and death (9.7 percent of warfarin participants vs. 4.3 percent of aspirin participants) during an average follow-up time of 1.8 years. The percentages of participants having a stroke during the study were 20.7% on aspirin and 17.6% on warfarin.
"This study is likely to have a significant impact on physician practices for patients with narrowed blood vessels leading to the brain," Dr. Chaturvedi said.
The researchers point out that warfarin is still a useful treatment for a variety of disorders, including atrial fibrillation. Patients who have questions about the use of warfarin should consult their doctors before making any decisions about altering their prescription regimens.
The researchers note that the costs to treat intracranial arterial stenosis would be reduced by using aspirin instead of warfarin. Not only is warfarin more expensive to purchase, repeated blood tests must be also done while taking the drug. Expenses climb again for treatment of increased complications of warfarin compared to aspirin. The researchers estimate that these savings could amount to at least $20 million per year.
The research group is now planning another study that will evaluate the use of stenting (using a device to hold the blocked arteries open) to treat stroke related to narrowed brain arteries, in the hope that it will prove more effective than existing therapies.