Aspirin Found to Beat Warfarin for One Kind of Stroke

Aspirin is as good as the anticoagulant drug warfarin at preventing strokes caused by partial blockage of arteries in the brain, and it is much safer, according to the first clinical trial comparing the two treatments.

The trial was halted prematurely, in fact, because of hemorrhaging and deaths associated with using warfarin, researchers report today in the New England Journal of Medicine.

The partial blockage, called intracranial arterial stenosis, causes about 90,000 strokes among Americans every year -- about 10% of all strokes.

Currently, physicians prescribe the two drugs equally to treat such patients, but the new findings should tip the balance strongly in favor of aspirin, said Dr. Marc I. Chimowitz of Emory University, who led the study.

Dr. Stanley N. Cohen, director of the stroke program at Cedars-Sinai Medical Center, said he had already switched to using aspirin as a first-line treatment.

“Now we know we are not doing patients any good” by using warfarin, he said.

Physicians said the findings should have no effect on other uses for warfarin. It is more effective at treating strokes caused by atrial fibrillation, a fluttering of the heart’s atrial valve that can produce blood clots that may cause a stroke when they enter the brain. Warfarin’s effectiveness is one reason why neurologists prescribe it to treat strokes caused by stenosis, said Dr. Michael R. Frankel of Emory, one of the study’s co-authors. Doctors assumed that if it was good for the heart, it was good for the brain. Early studies seemed to back that conclusion.

Researchers were surprised to find that their assumption was incorrect.

In a study sponsored by the National Institute of Neurological Diseases and Stroke, the team enrolled 569 patients who had suffered either a transient ischemic attack -- a so-called mini-stroke that is often a precursor of a more serious stroke -- or a non-disabling stroke. All patients had at least a 50% blockage in a major intracranial artery.

Half the patients received 1,300 milligrams of aspirin per day (a normal tablet has 325 milligrams) and half received a conventional dosage of warfarin.

After about 1.8 years of follow-up, 20.7% of those receiving aspirin had a stroke, compared to 17.6% of those receiving warfarin. But 8.3% of those receiving warfarin had a major bleeding incident and 9.7% died, compared to 3.2% and 4.3% of the aspirin users, respectively.

The increased risks from warfarin led Chimowitz and his colleagues to stop the trial.

In an editorial in the same issue of the journal, Dr. Walter J. Koroshetz of Massachusetts General Hospital in Boston applauded the findings but noted that the study’s physicians had difficulty maintaining the proper level of warfarin in patients’ bloodstreams. A therapeutic level was maintained 63% of the time.

But that is exactly the point, Cohen said. Warfarin requires constant monitoring to assure that the proper amount is in the blood, he said. If levels are too low, the drug is ineffective. If they get too high, massive bleeding can result. Some foods, particularly those containing vitamin K, also can interfere with the drug.

Even with the close monitoring required by the study, doctors achieved the correct level 63% of the time, Cohen said.

“In the real world, you are not going to get close to that,” he said. “But even if you forget your aspirin sometimes and only take it three days a week, you’ve got enough,” Cohen said.