After a decade of earlier research that verified the benefit of the blood thinner warfarin, physicians now routinely prescribe the drug to prevent first and recurrent strokes in individuals who have atrial fibrillation, a condition characterized by an irregular and rapid rhythm in the atrial chambers of the heart.
People with atrial fibrillation are at risk for stroke because pooled blood in their hearts can lead to clots, which, when dislodged and carried to the brain in a process known as embolism, can occlude brain arteries and block blood flow. The resultant brain damage is known as an ischemic stroke.
Because warfarin use can produce complications, such as hemorrhage, many physicians have been hesitant to use it even in atrial fibrillation. Until now, though, no research has compared warfarin's value with aspirin in the prevention of stroke in people who do not have atrial fibrillation yet who have had an ischemic stroke.
Approximately 8 percent of patients with ischemic stroke who do not have atrial fibrillation but who take aspirin get a recurrent stroke within a year's time.
A study that began eight years ago, led by Dr. J. P. Mohr, the Sciarra Professor of Clinical Neurology at Columbia University College of Physicians & Surgeons and head of the Neurovascular Center at Columbia-Presbyterian Medical Center of NewYork-Presbyterian Hospital, aimed to determine if warfarin-- successful with atrial fibrillation patients in stroke prevention--might do better than aspirin in preventing recurrent ischemic stroke in patients without atrial fibrillation.
The results of the study, however, show no significant difference between the two drugs in their ability to prevent recurrent strokes in patients who have had an ischemic stroke but who did not have atrial fibrillation. The findings of the $35 million study, which followed patients for two years, are being reported in the Nov. 15th issue of the New England Journal of Medicine.
The study followed 2,206 individuals who had suffered from an ischemic stroke due either to local blockage in the brain vessels from hardening of the arteries or from a clot arising from a source outside the brain carried through arteries to the brain vessels.
The study did not include patients whose stroke was associated with atrial fibrillation (approximately 15 percent of all cases of stroke) or from any form of hemorrhage (approximately 20 percent of all cases of stroke). Ischemic stroke patients without atrial fibrillation represent approximately 65 percent of all cases of stroke.
In the double-blind study, the pills were indistinguishable so that neither patients nor investigators knew who received which medication. Since individuals who take warfarin need to have their blood monitored for its ability to clot, the investigators were sent true laboratory values for patients actually on warfarin and false values for the aspirin recipients.
After analyzing the data, the researchers found no statistically significant differences between the two groups of patients in the risk in having a subsequent stroke. No statistically significant difference was seen in the risk of major bleeding in either of the two groups.
Aspirin, with its low cost, wide availability, ease of use, and lack of need for monitoring compared to warfarin, may remain the most widely used of two drugs, Dr. Mohr says. Aspirin's use in combination with other drugs having a similar anti-clotting action seems promising in preventing stroke, he adds. However, he also stressed that earlier concerns that warfarin was more hazardous than aspirin because of warfarin's potential for hemorrhage proved unfounded at the doses used in the study.
Those physicians having other indications for warfarin therapy, such as in patients who have artificial heart valves or pulmonary embolism, should take comfort in its comparative safety and efficacy even when no atrial fibrillation is present and have no reason to switch to aspirin should a stroke occur, Mohr says.
Although both drugs provide a reduction in the risk of having another stroke, this study showed that at least 8 percent of the patients taking either warfarin or aspirin still will get another stroke in a year's time. Dr. Mohr says further research at Columbia and elsewhere is ongoing to develop new methods to reduce this continuing recurrence rate.
·Stroke is the third largest cause of death in the United States, ranking behind "diseases of the heart" and all forms of cancer, according to the American Heart Association.
·Stroke is a leading cause of serious long-term disability in the United States, the heart association says.
·The heart association says approximately 500,000 people suffer a new stroke each year; an additional 100,000 cases are recurrent attacks.
·The National Institute of Neurological Disorders and Stroke funded the trial.
·Bayer provided aspirin and placebo aspirin at no cost for the study.
·DuPont donated the warfarin and placebo-warfarin and provided $600,000 for the formulation of both medications used in the trial.
Journal
New England Journal of Medicine