National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), have shown for the first time that aspirin works as well as warfarin in reducing blood clotting. Until now doctors have lacked good evidence for choosing one therapy over the other.
For many years aspirin and warfarin have been used in order to reduce the risk of stroke, partial blockage of arteries in the brain (intracranial stenosis). Now, results of a double-blind, randomized clinical trial show for the first time that aspirin works as well as warfarin with fewer side effects.
John R. Marler, M.D., the Associate Director for Clinical Trials at NINDS says the trial is good news in that a simple low-cost drug works just as well as one that requires complicated and expensive monitoring and dose adjustments. The study appears in the March 31, 2005, issue of the New England Journal of Medicine.
Intracranial stenosis is caused by atherosclerosis - fatty deposits that build up on the inner walls of the arteries and restrict blood flow and 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. Studies in the 1950s suggested that anticoagulants (a class of drugs that reduce blood clotting), such as warfarin, can reduce the risk of stroke in people with this disease.
In the new study, called the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial, investigators at 59 medical centres across the United States, led by Marc I. Chimowitz, M.D., of Emory University in Atlanta, compared warfarin to 1300 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 enrolment in the study.
They found that about 22 percent of the patients had a subsequent ischemic stroke (caused by blockage of an artery), brain haemorrhage, or death from other blood vessel-related causes, regardless of whether they received aspirin or warfarin. However, the rates of major haemorrhage and death from all causes were significantly higher in the patients treated with warfarin. The safety of the patients given warfarin did cause the study to be terminated earlier than originally planned on the recommendation of an independent Data and Safety Monitoring Board.
Dr. Chimowitz estimates that as the 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. He says the results are only relevant to people with intracranial stenosis and 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.
The dose of aspirin used in this study - 1300 mg - is much higher than the daily doses typically prescribed and while there is some concern that doses may increase the risk of gastrointestinal bleeding, this dose was used because it was the only one known to be as effective as warfarin for this disease and was similar to the major bleeding risk in other stroke trials that have evaluated lower doses of aspirin.
Most experts believe there are no advantages to aspirin doses greater than 325 mg for stroke prevention, and the FDA's 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.
The researchers say that 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.