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 led by researchers in the Emory University Schools of Medicine and Public Health and published in the New England Journal of Medicine on March 31, 2005.
Funded by the National Institute of Neurological Disorders and Stroke (NINDS), 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 WASID or Warfarin-Aspirin Symptomatic Intracranial Disease study.
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 U.S. 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.
Marc Chimowitz, MD, a professor of neurology at Emory University School of Medicine, led the WASID study. "Our goal was to answer a question that has been asked by neurologists for over 20 years: Is warfarin more effective than aspirin for preventing stroke related to narrowed brain arteries?" says Dr. Chimowitz. "Uncertainty about the answer is reflected in a recent survey we conducted which suggests that about 50 percent of neurologists in the U.S. use warfarin as first-line treatment for this disease and 50 percent use aspirin or another anti-platelet agent."
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, though 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.
"This study was planned and implemented so, in the end, physicians would better know how to advise patients who may be at risk of stroke related to narrowed brain arteries," says Michael Lynn, M.S., Department of Biostatistics in the Rollins School of Public Health at Emory, who led the data analysis and management team. "Because of the excellent work by all of the centers involved and dedicated participants willing to contribute to our research effort, we were able to conduct a scientifically rigorous study."