EMBARGOED FOR RELEASE
Wednesday, November 14, 2001
5:00 p.m. EST
Margo Warren or Marian Emr
"Treatment is far superior to no treatment and treatment with either aspirin or warfarin is safe under carefully monitored conditions," says J. P. Mohr, M.D., director of the Stroke Unit at New York's Columbia University and lead investigator of the trial.
Both drugs slow clotting of the blood, and blood clots are involved in the final stages of the most common type of stroke due to blockage of the vessels that supply oxygen-rich blood to the brain. Aspirin affects the blood platelets, while warfarin inhibits circulating clotting proteins in the blood. Aspirin has been used for over 100 years, but its beneficial effects to prevent stroke and heart attack only started to be recognized in the 1970s. Whether warfarin was superior to aspirin for stroke prevention was unclear prior to WARSS. Numerous previous studies have proven that use of aspirin reduces recurrent stroke by about 25 percent. Part of the controversy about aspirin versus warfarin for stroke prevention has been the thinking among clinicians that warfarin may be a better blood thinner than aspirin to prevent almost all forms of stroke, but that it has greater side effects, increased risk of hemorrhage, and higher costs due to the need for blood tests to monitor the treatment effect for patients.
An earlier NINDS trial, Stroke Prevention in Atrial Fibrillation Study (SPAF), cleared up some of the confusion by showing a distinct benefit of warfarin over aspirin in preventing recurrent stroke in patients whose stroke was related to atrial fibrillation (AF) strokes caused by clots coming from the heart. About 15 percent of stroke patients have this heart rhythm abnormality, a condition in which the two upper chambers of the heart (the atria) do not have a rhythmic, forceful beat, and the pulse is irregular. Although the superior efficacy of warfarin versus aspirin in preventing recurrent stroke in patients with atrial fibrillation was confirmed in SPAF, greater insight was needed to determine optimal therapy in preventing recurrent stroke in the larger number of patients without clots in the heart, which was the purpose of the WARSS study.
"We had evidence that patients with AF should be taking warfarin, but we didn't know which medicine to recommend to stroke patients without AF," said John R. Marler, M.D., Associate Director for Clinical Trials for the NINDS. "This scientifically sound definitive clinical trial provides important information in the fight against stroke. It supports the widespread use of aspirin and other antiplatelet drugs, but it demonstrates an equally efficacious alternative, appropriate for selected patients," he added.
To make the aspirin and warfarin arms of the study as unbiased as possible, the investigators matched both groups of patients for primary stroke severity, age, gender, education, and race/ethnicity. The two groups were also matched for stroke risk factors, including hypertension, diabetes, cardiac disease, smoking, alcohol consumption, and physical activity. The investigators used an aspirin dose of 325 mg/day and a warfarin dose specifically tailored to each individual patient, and a double-blind plan in which neither the treating doctor nor the patient knew which treatment was being received.
The study included patients who had strokes due to small vessel lacunar infarcts, the predominant type of stroke in people with diabetes; strokes due to large artery atherosclerosis (build-up of cholesterol plaques); and cryptogenic stroke of undetermined cause. The study excluded patients with atrial fibrillation, those with a blood clot in the heart, and those eligible for carotid endarterectomy surgery. For these patients, appropriate treatment guidelines already exist from earlier NINDS-sponsored clinical trials. For safety, patients with a history of severe bleeding from any cause and patients whose strokes were related to surgical procedures were not included in the trial.
Several subsets of patients seemed to show slight benefits from one of the two therapies, but neither of the treatments showed a difference greater than would be expected from chance alone. The lacunar infarct and small vessel disease subgroup seemed to fare better with aspirin, as did, to a lesser extent, the large artery disease subgroup. The cryptogenic subgroup appeared to fare better with warfarin, but investigators believe some of these patients have a tendency to form blood clots in the heart. Four parallel studies for WARSS are looking for groups of patients who might gain more benefit from warfarin or aspirin. Additional analysis of the WARSS data may point to differences in the ability of aspirin and warfarin to prevent stroke for some patients. Overall, there was no evidence of significant differences between the two drugs.
Stroke is the third leading cause of death in the United States and the leading cause of serious, long-term disability. Approximately 600,000 new strokes are reported in the United States annually and about 160,000 Americans die each year from stroke.
Bristol-Myers Squibb Company provided an unrestricted educational grant for this study.
The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system. The NINDS is now celebrating its 50th anniversary.
This release will be posted on EurekAlert! at http://www.eurekalert.org and on the NINDS website at http://www.ninds.nih.gov/news_and_events/index.htm.