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Preventing Stroke: The Choice Between Aspirin and Warfarin


For release: Tuesday, April 21, 1998

A new study outlines the criteria for identifying hundreds of thousands of Americans who have the most or least to gain from the use of anticoagulants such as warfarin to prevent stroke. The study identifies certain patients with a common type of irregular heartbeat called atrial fibrillation, and a low-risk for stroke who fare well by taking aspirin instead of warfarin to prevent stroke. Previous studies have shown that warfarin can cut by two-thirds the stroke risk in patients with atrial fibrillation who are at high risk for stroke. However, because treatment with aspirin carries a lower risk of bleeding and requires less medical monitoring than warfarin, doctors have been interested in identifying the specific group of patients who would do well on aspirin alone.

People with atrial fibrillation are six times more likely to have a stroke than people without, and account for as many as 80,000 strokes a year.

The findings are from Part III of a decade-long study called Stroke Prevention in Atrial Fibrillation (SPAF), designed to find the best way to reduce strokes in the 2 million Americans who have atrial fibrillation. This series of clinical trials is funded by the National Institute of Neurological Disorders and Stroke (NINDS). All of the SPAF studies look at preventive treatment with aspirin and warfarin, both of which lessen the tendency of blood to clot. The latest research appears in the April 22, 1998, issue of The Journal of the American Medical Association.* SPAF is coordinated by Robert G. Hart, M.D., and David G. Sherman, M.D., from the University of Texas Health Sciences Center at San Antonio.

"Stroke prevention research is absolutely vital. The number of strokes has risen so dramatically in recent years that we must find ways to stop strokes from happening in the first place," said Audrey Penn, M.D., Acting Director of the NINDS.

A group of 892 low-risk atrial fibrillation patients in the study took a daily dose of adult aspirin and were evaluated for an average of 2 years to see if they had a stroke or developed a systemic embolism, a clot causing sudden blockage of arterial blood supply to a limb or body organ (blood clots are the cause of 80 percent of all strokes). Investigators found that the rate of ischemic stroke or embolism among these patients was 2.2 percent a year, only slightly higher than the 1 percent rate experienced by the general population in this age range. However, for patients with hypertension, but none of the four other risk factors, the rate of strokes or embolism was significantly higher -- 3.6 percent. The rate of disabling stroke, however, was low in both groups.

The researchers concluded that, while hypertension in atrial fibrillation patients is a significant predictor of stroke, it remains to be seen whether these patients should take aspirin or warfarin. The final treatment decision should be made between the physician and the patient after considering the individual's risk for stroke, benefits from treatment, and personal preferences.

Higher-risk patients, who have one or more specified risk factors, suffer strokes at a rate of 8 percent a year, and through previous SPAF studies have been shown to benefit greatly from treatment with warfarin.

The study estimates that for every 1,000 atrial fibrillation patients in the low risk category, about five ischemic strokes would be prevented among those taking aspirin and three major hemorrhages would occur. If these same patients were given warfarin instead of aspirin over a 1-year period, about 10 ischemic strokes would be prevented, but the treatment might cause 10 to 12 major hemorrhages.

"When someone is prescribed warfarin for stroke prevention, it often means a 20-year commitment to taking the drug, and the risk of bleeding goes up every year you're on it," said Dr. Sherman. "For this reason, we have been eager to find exactly which patients will do well on aspirin therapy and I think this study identifies them with certainty."

In people with atrial fibrillation, blood clots can form in the upper chambers of the heart. These clots can break loose, be pumped into the bloodstream, and carried to the brain where they can cause a stroke. Atrial fibrillation primarily affects people over the age of 60 and is diagnosed by electrocardiogram. While some people have no symptoms, most experience a sensation of rapid heart beats or skipped beats.

The SPAF trials, which started in 1987, have involved about 4,000 patient volunteers with atrial fibrillation at 25 medical centers in the United States and Canada. Results from SPAF I, reported in 1990, found an 80 percent reduction in stroke risk for persons with atrial fibrillation who receive treatment with aspirin or warfarin. The SPAF II study, reported in 1994, identified the 60 percent of people with atrial fibrillation for whom a daily adult aspirin provides adequate protection against stroke with minimal complications. This group consists of those younger than 75 and those older than 75 with no additional stroke risk factors such as high blood pressure or heart disease. SPAF III studied the remaining 40 percent of atrial fibrillation patients who had additional risk factors for stroke.

The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system and is a lead agency for the Congressionally designated Decade of the Brain.

Stroke Prevention in Atrial Fibrillation Investigators. "Prospective Identification of Patients with Nonvalvular Atrial Fibrillation at Low Risk of Stroke During Treatment with Aspirin: Stroke Prevention in Atrial Fibrillation III Study." JAMA, Vol. 279, No. 16, April 22/29, 1998, pp. 1273-1277.

Originally prepared by Margo Warren, NINDS Office of Communications and Public Liaison.

Last Modified August 7, 2009