Aspirin effective as warfarin in treating intracranial stenosis
Aspirin showed fewer side effects
Researchers in a new clinical trial say it shows for the first time that aspirin works as well as warfarin (Coumadin) in treating intracranial stenosis — but with fewer side effects.
The study, which was funded by the National Institute of Neurological Disorders and Stroke (NINDS), appeared in the March 31 issue of the New England Journal of Medicine (NEJM).
In the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial, investigators at 59 medical centers across the United States compared warfarin to 1,300 mg per day of aspirin in 569 patients for an average of 1.8 years. All of the patients had a greater than 50% blockage of a major intracranial artery and had experienced a transient ischemic attack (TIA) or nondisabling stroke within the 90 days prior to their enrollment in the study.
The investigators found that 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. 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% vs. 8.3% for major hemorrhage, 4.3% vs. 9.7% for death, and 2.9% vs. 7.3% for myocardial infarction or sudden death). Enrollment in the study was terminated early because of concern for the safety of the patients given warfarin.
The 1,300 mg dose of aspirin given to patients is much higher than the dose typically prescribed, which is usually in the 81 mg to 325 mg range. The researchers had concern about the high dose increasing the risk of gastrointestinal bleeding, but found the dose supported in other studies. "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 Marc I. Chimowitz, MD, an associate professor of neurology at Emory University in Atlanta, in a NINDS statement. 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, he adds.
The results of this trial have important implications for clinical practice, according to the researchers. "First, aspirin (at the 1,300 mg recommended dose), rather than warfarin, should be used to treat intracranial arterial stenosis," they say. "Using aspirin rather than warfarin in these patients will substantially lower the risk of major hemorrhage and eliminate the inconvenience of using warfarin." It also will result in considerable savings by avoiding the costs of warfarin, INR testing, and treatment of warfarin-associated hemorrhages.
The researchers also question the role of vascular imaging of the intracranial vessels as part of the initial evaluation of patients with TIA or stroke, saying the imaging may be unnecessary. But then they reconsider. "On the other hand, identification of patients with intracranial stenosis has important prognostic implications, may influence treatment decisions (such as those regarding high-dose aspirin and aggressive risk-factor management), and may ultimately lead to more effective therapies for this high-risk disease," they say.
In an accompanying editorial in the NEJM, a neurologist agrees with the latter statement. "Concluding, on the basis of the WASID data, that there is no reason to obtain images of the intracranial vessels to diagnose this high-risk condition does not seem warranted, especially since the study did not address management of the commonly unstable, acute phase of symptomatic intracranial stenosis," says Walter J. Koroshetz, MD, director of Stroke Service at Massachusetts General Hospital in Boston and professor of neurology at Harvard Medical School.
The WASID data show that warfarin is not superior to 1,300 mg of aspirin in a population study, he continues. "Because the result may well be related to the inadequate time in the INR target range with warfarin, as opposed to a general ineffectiveness of anticoagulation, it does not preclude a trial of very carefully regulated anticoagulation in patients who continue to have recurrent ischemic events in the territory of the index vessel, despite antiplatelet therapy."
The patients and the investigators deserve a great deal of credit for participating in and carrying out this difficult study, Koroshetz concludes. "The messages at this point are that symptomatic intracranial atherosclerosis is a mark of aggressive vascular disease, that aspirin is an imperfect therapy, and that anticoagulation looks very promising but is difficult to achieve."
Researchers in a new clinical trial say it shows for the first time that aspirin works as well as warfarin (Coumadin) in treating intracranial stenosis but with fewer side effects.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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