Aspirin more effective than warfarin for some patients

Washington -- A new study comparing treatments to reduce the risk of stroke due to blockage of the brain's arteries may tip the balance toward using aspirin and away from the more expensive and complex warfarin regimen.

Results of a double-blind, randomized clinical trial published in the March 31 New England Journal of Medicine found that aspirin is safer than warfarin and just as effective for treating intracranial stenosis.

"The trial is good news. A simple, low-cost drug works just as well as one that requires complicated and expensive monitoring and dose adjustments," said John R. Marler, MD, the associate director for clinical trials at the National Institute of Neurological Disorders and Stroke, which funded the study.

Intracranial stenosis causes about 10% of the 900,000 strokes and transient ischemic attacks that occur in the United States each year. People who have a stroke or a TIA due to this condition, which is particularly common among blacks and Asians, also have an increased risk of a second stroke -- as great as 15% each year after the first incident occurs.

The trial came at a good time, said lead author Dr. Marc I. Chimowitz, a professor of neurology at Emory University School of Medicine in Atlanta. About 50% of the neurologists in the country use warfarin, or coumadin, and 50% use aspirin, he said. "No one really knew what the right answer was."

Plus the finding actually runs counter to that of a pilot study that found warfarin was the preferred treatment, he added.

Dr. Chimowitz's Warfarin Aspirin Symptomatic Intracranial Disease -- WASID -- trial settled the matter in his view. "I will not use warfarin anymore as a first-line therapy. I am now recommending 1,300 mg of aspirin per day, which is four enteric-coated, regular aspirin."

Acknowledging that a 1,300 mg dose of aspirin is high, Dr. Chimowitz said that when the trial was begun in 1999, such doses were generally more acceptable. "Since that time the pendulum has swung and more people would like to use low-dose aspirin. But we still think there are some theoretical reasons why high-dose aspirin may be best for this disease." Overcoming aspirin resistance is one of those reasons, he said.

The trial enrolled 569 people at 59 medical centers across the United States and Canada where investigators compared treatment with warfarin and treatment with aspirin for an average of 1.8 years. All those enrolled had a greater than 50% blockage of a major intracranial artery and had experienced a TIA within 90 days prior to their study enrollment.

The trial was to have enrolled more than 800 patients but safety concerns led the study's independent monitoring committee to stop enrollment at 569. Specifically, investigators found that while about 22% of the patients had a subsequent ischemic stroke, brain hemorrhage or death from other blood-vessel-related causes, regardless of whether they received aspirin or warfarin, the rates of major hemorrhage and death from all causes were significantly higher in the patients treated with warfarin.

For example, during the follow-up period, 4.3% of patients in the aspirin group had died, compared with 9.7% in the warfarin group. Complications also included higher rates of bleeding in the warfarin group.

Warfarin remains useful

"This study is likely to have a significant impact on physician practices for patients with narrowed blood vessels leading to the brain," said Seemant Chaturvedi, MD, associate professor of neurology at Wayne State University School of Medicine in Detroit. Dr. Chaturvedi led the Detroit-area portion of the study and served on the study's steering committee.

The researchers estimate that a major shift to treatment with aspirin rather than warfarin could save more than $20 million per year in health care expenses.

However, warfarin is still the treatment of choice for patients with other stroke conditions, such as atrial fibrillation or clots in the legs or lungs, the researchers stressed.

Although many physicians had favored treating patients with symptomatic intracranial stenosis with warfarin in the not-too-distant past, a more recent trend was to move away from warfarin, said Rafael H. Llinas, MD, assistant professor of neurology at Johns Hopkins School of Medicine in Baltimore.

The difficulty of monitoring the correct dose of warfarin was a major reason for this shift, he said.

The study results will likely mean that physicians will prescribe warfarin only for people who have failed aspirin therapy or are continuing to have small strokes even though they are on maximum dose aspirin, said Dr. Llinas.

Walter J. Koroshetz, MD, director of stroke services at Massachusetts General Hospital and the author of an editorial that accompanied the March 31 New England Journal of Medicine article, noted that the study data also suggest that participants whose warfarin dose was kept within the correct therapeutic range demonstrated a striking reduction in the risk of cerebrovascular and cardiovascular events.

However, that target range is notoriously difficult to achieve consistently, he said.

The study revealed that patients on long-term warfarin therapy can be expected to be at target range only 63% of the time -- a finding that might be surprising to primary care physicians, said Dr. Koroshetz.