Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.

Department of Neurology, School of Medicine, Emory University, Atlanta, USA.
New England Journal of Medicine (Impact Factor: 54.42). 04/2005; 352(13):1305-16. DOI: 10.1056/NEJMoa043033
Source: PubMed

ABSTRACT Atherosclerotic intracranial arterial stenosis is an important cause of stroke. Warfarin is commonly used in preference to aspirin for this disorder, but these therapies have not been compared in a randomized trial.
We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin (target international normalized ratio, 2.0 to 3.0) or aspirin (1300 mg per day) in a double-blind, multicenter clinical trial. The primary end point was ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke.
After 569 patients had undergone randomization, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin. During a mean follow-up period of 1.8 years, adverse events in the two groups included death (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group; hazard ratio for aspirin relative to warfarin, 0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02), major hemorrhage (3.2 percent vs. 8.3 percent, respectively; hazard ratio, 0.39; 95 percent confidence interval, 0.18 to 0.84; P=0.01), and myocardial infarction or sudden death (2.9 percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.02). The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group (P=0.16); the rate of death from nonvascular causes was 1.1 percent and 3.8 percent, respectively (P=0.05). 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 (hazard ratio, 1.04; 95 percent confidence interval, 0.73 to 1.48; P=0.83).
Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial. Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from its early stages and to identify new potential therapeutic targets for this condition.
    BMC Neurology 02/2011; 11:22. · 2.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intracranial atherosclerotic disease (ICAD) is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%-99%) stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population.
    Stroke research and treatment. 01/2011; 2011:282845.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To test whether symptomatic severe intracranial atherosclerotic stenosis was associated with a higher subsequent stroke risk than moderate stenosis after elective angioplasty with a balloon-expandable stent and to explore which factors were associated with the subsequent stroke. Between September 2001 and June 2005, there were 220 symptomatic intracranial atherosclerotic stenoses in 213 patients undergoing elective stenting at our institute. Of these stenoses, 126 in 121 patients were > or =70% severe stenoses, and 94 in 92 patients were 50% to 69% moderate stenoses. Primary endpoints included lesion-related ischemic stroke, and symptomatic brain or subarachnoid hemorrhage. Ten primary endpoint events occurred in the severe stenosis group (six within 30 days and four in mean follow-up of 26.0 months after 30 days), and seven occurred in the moderate stenosis group (four within 30 days and three in mean follow-up of 27.6 months after 30 days). There was no significant difference in cumulative probability of primary endpoints between the severe (7.2% at 1 year and 8.2% at 2 years) and moderate (5.3% at 1 year and 8.3% at 2 years) stenosis groups. No single factor was found to be associated with primary endpoints in the moderate stenosis group. Multivariable analysis revealed that stent failure was the only predictor of primary endpoints in the severe stenosis group (hazard ratio 5.31, 95% CI 1.35 to 20.91). Symptomatic severe intracranial atherosclerotic stenosis did not present a higher subsequent stroke risk than moderate stenosis after elective angioplasty with a balloon-expandable stent. Patients with severe stenosis may benefit from successful stent placement, and randomized trials are necessary to demonstrate this possible benefit.
    Neurology 02/2007; 68(6):420-6. · 8.30 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014