Status:
Trial complete. Results published in March 2005.
Purpose:
To compare the prophylactic efficacies of warfarin and aspirin against stroke and vascular death in patients with symptomatic stenosis of a major intracranial artery.
Location(s):
Alabama, Arizona, Arkansas, California, Quebec, Ontario, British Columbia, Florida, Georgia, Illinois, Indiana, Louisiana, Maine, Maryland, Massachusetts, Michigan, Mississippi, Missouri, New York, North Carolina, Ohio, Pennsylvania, Rhode Island, Tennessee, Texas, Virginia, Wisconsin
Year Started:
2000
Design:
Prospective, double-blind, randomized, multi-center trial.
Inclusion Criteria
Patients who present within 90 days of a transient ischemic attack (TIA) or non-severe stroke attributed to angiographically-proven high-grade (50 - 99%) stenosis of a major intracranial artery (internal carotid artery, middle cerebral artery stem, vertebral artery, or basilar artery), and who have a modified Rankin Scale (MRS) score > 3, are eligible for this study.
Exclusion Criteria
Females of childbearing potential and persons with > 50% stenosis of the ipsilateral external carotid, isolated stenosis of the anterior cerebral artery, posterior cerebral artery, middle cerebral artery (MCA) division, or a distal branch of the MCA, who have intracranial or extracranial arterial dissection, Moya Moya disease, vasculitis, radiation-induced vasculopathy, or fibromuscular dysplasia, who have any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, or left atrial spontaneous echo contrast, who have any of the following contraindications to the use of either warfarin or aspirin: active peptic ulcer disease, active bleeding diathesis, platelets < 100,000/mm3, hematocrit < 30, a clotting factor abnormality that increases the risk of bleeding, alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic hemorrhage within the past year, severe liver impairment (SGOT > 3x normal, cirrhosis), allergy to aspirin or warfarin, uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115mm Hg), positive stool GUAIAC that is not attributable to hemorrhoids, or plasma creatinine > 3.0, who require intravenous heparin after randomization, who have a severe neurological deficit, dementia, or psychiatric problem that precludes living independently and reliably following an outpatient program, who have a co-morbid conditions that may limit survival to less than 5 years, or who are enrolled in another study, will be excluded from this trial.
Patient Involvement:
All participants must undergo conventional angiography to determine the degree af arterial stenosis. Eligible patients will be randomized to receive either aspirin 1300 mg/day or warfarin, titrated to an International Normalized Ratio (INR) of 2 - 3. All patients will receive monthly bloodtests, and will be evaluated by a neurologist every four months, until the end of the trial.
Primary Outcome:
Incidence of ischemic stroke, hemorrhagic stroke, and vascular death.
Secondary Outcome:
Incidence of vascular death and disabling stroke, all stroke, all ischemic stroke, myocardial infarction, major systemic hemorrhage, intracranial hemorrhage, and ischemic stroke in the territory of the stenotic intracranial artery.
Results:
For the primary endpoints; there was 4.3% rate of death in the aspirin group and a 9.7% rate in the warfarin group (P=0.02); there was a 3.2% rate of major hemorrhage in the aspirin group and a 8.3% rate in the warfarin group (P=0.01); and there was a 2.9% rate of myocardial infarction or sudden death in the aspirin group vs. a 7.3% rate in the warfarin group (P=0.02). For all vascular deaths, there was a 3.2% rate in the aspirin group and a .9% rate in the warfarin group (P=0.16). The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group (P=0.83).
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Source of Information:
NIH Grants Database and presented at the 25th International Stroke Conference (February 2000). Stroke. 2000;31:2536. Published report.
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