"Warfarin vs. Aspirin in Patients with Recurrent Ischemic Stroke".The New England Journal of Medicine. 2001. 345(20):1444-1451.PubMed•Full text•PDF

Contents

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 Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with prior noncardioembolic ischemic stroke, is warfarin superior to aspirin in preventing recurrent ischemic stroke or death?

Bottom Line

In patients with prior noncardioembolic ischemic stroke, warfarin was not superior to aspirin in preventing recurrent ischemic stroke or death and both were considered reasonable therapeutic alternatives.

Major Points

Guidelines

As of 2001, guidelines have not been updated to reflect the results of this trial.

Design

- Multicenter, double-blind, randomized trial
- N=2,206 patients with recent ischemic stroke
- Warfarin (target INR 1.4 to 2.8)
- Aspirin (325 mg per day)
- Enrollment: 1993-2000
- Mean follow-up: 2 years
- Analysis: Intention-to-treat
- Primary outcome: Composite of recurrent ischemic stroke or death from any cause within two years

Population

Inclusion Criteria
- Age 30-85 years
- Acceptable candidates for warfarin therapy
- Had an ischemic stroke within the previous 30 days
- Glasgow Outcome Scale score of 3 or higher

Exclusion Criteria
- Baseline INR >1.4
- Stroke due to high-grade carotid stenosis planned for surgery
- Stroke associated with inferred cardioembolic source, e.g., atrial fibrillation

Baseline Characteristics
- Similar between both treatment groups

Interventions

- Warfarin dose adjusted to maintain an INR 1.4 to 2.8
- Aspirin 325 mg daily

Outcomes

Primary Outcome
- No significant difference in the rate of recurrent ischemic stroke or death between warfarin and aspirin (17.8% with warfarin vs. 16.0% with aspirin, P=0.25)

Secondary Outcomes
- Rates of major hemorrhage were low and not significantly different between treatment groups
- Minor hemorrhages were more frequent in the warfarin group

Criticisms

- The study did not have sufficient power to show differences in treatment effects among various clinically identified stroke subtypes.

Funding

Supported by a grant from the National Institute of Neurological Disorders and Stroke. Medications and placebos were supplied by Dupont Pharmaceuticals and Bayer.

Further Reading

The original publication and accompanying editorial in "The New England Journal of Medicine" are suggested for further reading.