article155

WASID

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with symptomatic intracranial arterial stenosis, which antithrombotic treatment is more effective: aspirin or warfarin?

Bottom Line

Aspirin should be used in preference to warfarin for patients with symptomatic intracranial arterial stenosis as warfarin is associated with higher rates of adverse events and provides no additional benefit over aspirin.

Major Points

Guidelines

As a result of this trial, aspirin is recommended over warfarin in the treatment of symptomatic intracranial arterial stenosis.

Design

Multicenter, double-blind, parallel group, randomized, placebo-controlled trial.

Population

569 patients with symptomatic 50 to 99 percent intracranial arterial stenosis (carotid, middle cerebral, vertebral, or basilar arteries) confirmed by angiography.

Inclusion Criteria
Patients with transient ischemic attack or nondisabling stroke within 90 days before randomization, attributable to angiographically verified 50 to 99 percent stenosis of a major intracranial artery, with a modified Rankin score of 3 or less, and aged at least 40 years.

Exclusion Criteria
Exclusion criteria included tandem 50 to 99 percent stenosis of extracranial carotid artery, nonatherosclerotic stenosis of intracranial artery, cardiac source of embolism, contraindication to aspirin or warfarin therapy, indication for heparin post-randomization, and coexisting condition limiting survival to less than five years.

Baseline Characteristics
Comparable across treatment groups with a mean follow-up period of 1.8 years.

Interventions

Patients were randomly assigned to receive warfarin (target INR, 2.0 to 3.0) or aspirin (1300 mg per day).

Outcomes

Primary Outcomes
- The primary end point occurred in 22.1 percent of the aspirin group and 21.8 percent of the warfarin group (hazard ratio, 1.04; P=0.83).
- Rates of death from any cause were 4.3 percent in the aspirin group versus 9.7 percent in the warfarin group (hazard ratio, 0.46; P=0.02).
- Rates of major hemorrhage were 3.2 percent in the aspirin group versus 8.3 percent in the warfarin group (hazard ratio, 0.39; P=0.01).

Secondary Outcomes
- No significant differences between treatment groups in rates of ischemic stroke in any vascular territory, ischemic stroke in the territory of the stenotic intracranial artery, or composite of ischemic stroke, death from vascular causes other than stroke, or nonfatal myocardial infarction.
- Rate of major cardiac events (myocardial infarction or sudden death) was significantly higher in the warfarin group (hazard ratio, 0.40; P=0.02).

Criticisms

Funding

Funded by a grant from the National Institute of Neurological Disorders and Stroke, National Institutes of Health. Additional local support provided by several NIH-funded General Clinical Research Centers. Medications supplied by Bristol-Myers Squibb and Bayer, without direct funding.