Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
New England Journal of Medicine (Impact Factor: 55.87). 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.

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Available from: Vicki S Hertzberg, Sep 26, 2015
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    • "Intracranial atherosclerotic stenosis is one of the most common causes of ischaemic stroke worldwide [1]. Symptomatic intracranial atherosclerotic stenosis of ≥70% is associated with a high risk of recurrent stroke despite aggressive medical therapy [2], [3], [4]. As a means of preventing recurrent stroke, endovascular treatment remain to be considered potentially beneficial for patients with severe intracranial stenosis with insufficient collateral or with vulnerable plaque [5], [6], [7]. "
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    ABSTRACT: Objectives To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. Methods From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. Results Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5%) with acute thrombosis, 5 patients (1.8%) with subacute thrombosis, 17 patients (6.2%) with stroke, and 2 death (0.7%) in low-dose aspirin group, compared with no patient (0%) with acute thrombosis, 2 patient (2.1%) with subacute thrombosis, 6 patients (6.2%) with stroke, and 2 death (2.1%) in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. Conclusion Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.
    PLoS ONE 08/2014; 9(8):e105252. DOI:10.1371/journal.pone.0105252 · 3.23 Impact Factor
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    • "The warfarin–aspirin symptomatic intracranial disease (WASID) study showed that the role of medical therapy for intracranial atherosclerosis (≥70%) is less effective, with the 1-year risk of ischemic stroke remaining as high as 23% in patients who presented with stroke and 14% in patients who presented with transient ischemic attack (TIA) (2). Inspired by experience from the treatment of the coronary artery disease, Chinese doctors began treating patients with symptomatic intracranial artery stenosis refractory to medical therapy with endovascular treatment since the 1990s. "
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    ABSTRACT: Intracranial atherosclerotic disease (ICAD) accounts for 33-50% of all ischemic strokes in the Asian population (1) and represents an important public health issue in China. The results of the SAMMPRIS trial alarmed most experienced interventionalists in China for two reasons. Firstly, the high complication rate in the stenting arm (20% the first year) was higher than expected. Secondly, the recurrent stroke rate in the aggressive medical treatment arm at 12.2% during the first year was unacceptably high, not to mention the fact that such tight vascular risk factor control is difficult to achieve for many patients in real life clinical experience, at least in China. The experience of treating ICAD in China, gained over the last two decades, is very rich and promising. We intend to highlight these past experiences and address future trials and trends in China. We will also address our criticism of the SAMMPRIS trial design in order to better design a future trial.
    Frontiers in Neurology 07/2014; 5:129. DOI:10.3389/fneur.2014.00129
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    • "Researchers in WASID carried on a investigation, which prompted that in the case of intracranial artery stenosis, the involved vertebral basilar artery was 35–40% (12). There were also many limitations in studies of outcomes of posterior circulation atherosclerosis. "
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    ABSTRACT: Intracranial atherosclerotic disease was very common among stroke patients of Asians, Blacks, and Hispanics ancestry. Furthermore, stroke patients with intracranial atherosclerosis (ICAS) have higher recurrence rate of cerebral ischemia and death than those without ICAS. However, the natural history of intracranial atherosclerotic disease is still in controversy. Most of the studies were retrospective and randomized controlled trial of drugs. This review summarized the prognosis of symptomatic and asymptomatic intracranial atherosclerotic disease in order to guide clinical decision-making and further clinical research.
    Frontiers in Neurology 07/2014; 5:125. DOI:10.3389/fneur.2014.00125
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