PDF: WASID
(2005)Objective
Warfarin versus aspirin in patients with symptomatic intracranial arterial stenosis.
Study Summary
Intervention
Aspirin 1300 mg/day vs. warfarin titrated to INR 2.0–3.0. Blinded medication and INR monitoring through central lab; adverse events closely tracked.
Inclusion Criteria
Age ≥40, TIA or nondisabling stroke within 90 days attributed to 50–99% intracranial stenosis (carotid, MCA, vertebral, or basilar), mRS ≤3, and no cardioembolic source.
Study Design
Arms: Aspirin vs. Warfarin
Patients per Arm: Aspirin: 280, Warfarin: 289
Outcome
Bottom Line
Aspirin is safer and at least as effective as warfarin for preventing stroke and vascular death in patients with symptomatic intracranial stenosis. Warfarin was associated with significantly higher rates of death and major hemorrhage.
Major Points
- Landmark trial for intracranial atherosclerotic disease (ICAD) — 569 patients with symptomatic 50–99% intracranial stenosis randomized at 59 U.S. centers. Predecessor to SAMMPRIS.
- Qualifying vessels: intracranial ICA, MCA (M1 or M2), vertebral artery, or basilar artery — confirmed by conventional angiography. Vessel distribution: ~44% MCA, ~25% intracranial ICA, ~20% vertebral/basilar.
- Compared warfarin (INR 2.0–3.0) vs high-dose aspirin (1300 mg/day) for secondary prevention after TIA or nondisabling stroke within 90 days.
- Primary endpoint (ischemic stroke, brain hemorrhage, or vascular death): 22.1% aspirin vs 21.8% warfarin (HR 1.04, 95% CI 0.73–1.48, P=0.83) — no difference.
- Warfarin arm had significantly higher mortality (9.7% vs 4.3%, P=0.02), major hemorrhage (8.3% vs 3.2%, P=0.01), and MI (5.3% vs 2.1%, P=0.04). Trial stopped early for safety.
- Key secondary finding: 1-year stroke rate in aspirin arm was ~12% for 70–99% stenosis vs ~6% for 50–69% stenosis — established degree of stenosis as the strongest predictor of stroke risk in ICAD.
- WASID established aspirin as preferred over warfarin for ICAD and set the baseline event rates that informed SAMMPRIS design (which then showed aggressive medical management further reduced risk to ~5.8% at 30 days).
Study Design
- Study Type
- Randomized, double-blind, multicenter clinical trial
- Randomization
- Yes
- Blinding
- Patients, clinicians, and outcome assessors were blinded
- Sample Size
- 569
- Follow-up
- Mean 1.8 years (max 2 years)
- Centers
- 59
- Countries
- United States
Primary Outcome
Definition: Ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 22.1% (Kaplan–Meier estimated 2-year rate) | 21.8% | 1.04 (0.73–1.48) | 0.83 |
Limitations & Criticisms
- High-dose aspirin (1300 mg/day) is not commonly used in modern practice — 81–325 mg is standard. Unknown whether modern aspirin doses would show different results.
- Trial terminated early due to safety concerns in warfarin arm — limits power for long-term efficacy comparisons.
- No aggressive risk factor management protocol — unlike SAMMPRIS, WASID did not mandate specific BP or LDL targets, limiting assessment of optimized medical management.
- Conventional angiography was required for stenosis measurement — not reflective of modern practice using CTA/MRA.
- Findings apply to symptomatic ICAD only — cannot extrapolate to asymptomatic intracranial stenosis.
- Racially diverse cohort (27% Black, 13% Asian, 11% Hispanic) but all U.S. sites — may not generalize to East Asian populations where ICAD prevalence is higher.
- Did not test dual antiplatelet therapy (later addressed by SAMMPRIS).
- Mean follow-up only 1.8 years — insufficient for assessing long-term outcomes including stenosis progression.
Citation
N Engl J Med 2005;352:1305–1316