A double-blind, randomized clinical trial funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), shows for the first time that aspirin works as well as warfarin, but with fewer side effects.

"This trial is good news," says John R. Marler, M.D., the Associate Director for Clinical Trials at NINDS. "A simple, low-cost drug works just as well as one that requires complicated and expensive monitoring and dose adjustments."

Intracranial Stenosis

Intracranial stenosis is caused by atherosclerosis -- fatty deposits that build up on the inner walls of the arteries and restrict blood flow. Intracranial stenosis causes about 10 percent of the 900,000 strokes and transient ischemic attacks (TIAs) in the United States each year.

TIAs are transient strokes that last only a few minutes and occur when the blood supply to part of the brain is briefly interrupted. People with a stroke or TIA due to intracranial stenosis have a greatly increased risk of a second stroke -- as much as 15 percent per year.

Studies in the 1950s suggested that anticoagulants (a class of drugs that reduce blood clotting), such as warfarin, could reduce the risk of stroke in people with this disease.

Higher Death Rates with Warfarin

In the new study, the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial, Marc I. Chimowitz, M.D., of Emory University in Atlanta led a team of investigators at 59 medical centers across the United States who compared warfarin to 1,300 milligrams (mg) per day of aspirin in a total of 569 patients for an average of 1.8 years.

All of the patients had a greater than 50 percent blockage of a major intracranial artery and had experienced a TIA or non-disabling stroke within the 90 days prior to their enrollment in the study.

The investigators found that about 22 percent of the patients had a subsequent ischemic stroke (caused by blockage of an artery), brain hemorrhage, or death from other blood vessel-related causes, regardless of whether they received aspirin or warfarin.

However, the rates of major hemorrhage and death from all causes were significantly higher in the patients treated with warfarin (event rates for aspirin compared to warfarin, respectively, were 3.2 percent vs. 8.3 percent for major hemorrhage and 4.3 percent vs. 9.7 percent for death).

Enrollment in the study was terminated earlier than originally planned on the recommendation of an independent Data and Safety Monitoring Board because of concern for the safety of the patients given warfarin.

Only Relevant to Intracranial Stenosis

Since warfarin treatment is a more expensive and complicated therapy than aspirin, not using warfarin and preventing the bleeding complications associated with it would save more than $20 million per year in the United States, Dr. Chimowitz estimates.

"The results of this study are only relevant to people with intracranial stenosis," Dr. Chimowitz notes. People who are receiving warfarin for other conditions, such as an irregular heart rhythm (called atrial fibrillation) or clots in the legs or lung, should not stop taking the drug, as studies have found that it is the best option in those conditions, he cautions.

The dose of aspirin used in this study -- 1,300 mg -- is much higher than the daily doses typically prescribed, which range from 81 to 325 mg.

While there is some concern that doses of 1,300 mg aspirin may increase the risk of gastrointestinal bleeding, the investigators chose this dose because it was the only amount for which earlier studies had provided good preliminary data.

"This is the only dose we know is as effective as warfarin for this disease, since it was the only dose studied. We just don't know how other doses of aspirin would stack up," says Dr. Chimowitz.

The major bleeding risk on high-dose aspirin in WASID was similar to the major bleeding risk in other stroke trials that have evaluated lower doses of aspirin (e.g. 325 mg per day), he adds.

Most experts believe there are no advantages to aspirin doses greater than 325 mg for stroke prevention, and the US Food and Drug Administration-approved dose of aspirin for prevention of vascular events is 50-325 mg. Patients should consult their physicians before beginning any long-term or high-dose aspirin treatment regimen.

Better Therapies Needed

Even with treatment, the rates of ischemic stroke in this clinical trial were substantially higher than in stroke-prevention trials that have evaluated aspirin and warfarin in patients with other causes of stroke.

This underscores that patients with intracranial stenosis are at particularly high risk for stroke and that better therapies are needed, the investigators note.

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system.