PDF: ACST
(2004)Objective
To determine whether immediate carotid endarterectomy plus medical treatment versus medical treatment alone reduces stroke risk in patients with asymptomatic carotid stenosis
Study Summary
• Higher operative risks than ACAS: 3.0% vs 1.5% for stroke/death, 1.11% vs 0.14% for death
• Significant 2.5% reduction in disabling or fatal stroke, confirming CEA benefit in pragmatic setting
Intervention
Immediate carotid endarterectomy plus medical treatment versus medical treatment alone (surgery delayed until necessary)
Inclusion Criteria
Patients with ≥60% mainly asymptomatic carotid stenosis, assessed by Doppler ultrasonography using 'Uncertainty Principle'
Study Design
Arms: Immediate surgery group vs Medical treatment alone/delayed surgery group
Patients per Arm: 1560 per arm (3120 total)
Outcome
• Significant 2.5% reduction in disabling or fatal stroke (P=0.004)
• Greater benefit in men than women (interaction P=0.01)
Bottom Line
In 3,120 patients with asymptomatic carotid stenosis >60%, immediate CEA reduced 5-year risk of any stroke or perioperative death by 5.3% (95% CI 3.0-7.8%) vs medical management. Disabling/fatal stroke reduced by 2.5% (95% CI 0.8-4.3%; P=0.004). 30-day perioperative stroke+death was 3.0%. NNT ~40 to prevent 1 disabling/fatal stroke at 5 years. Benefit significant in men (OR 0.49) but not women (OR 0.96; interaction P=0.01). No benefit gradient with increasing stenosis severity (60-99%).
Major Points
- 5-year ARR for any stroke/perioperative death: 5.3% (95% CI 3.0-7.8%) — similar to ACAS (5.1%).
- First trial to show significant reduction in disabling/fatal stroke: ARR 2.5% (95% CI 0.8-4.3%; P=0.004).
- 30-day perioperative stroke+death: 3.0% — significantly higher than ACAS (1.5%; P=0.04), reflecting more pragmatic surgical standards.
- NNT ~40 to prevent 1 disabling/fatal stroke at 5 years.
- Clear sex difference: men benefited (OR 0.49; 95% CI 0.36-0.66) but women did not (OR 0.96; 95% CI 0.63-1.45); pooled interaction P=0.01.
- No benefit gradient with increasing stenosis (60-99%) — unlike symptomatic trials (NASCET/ECST). Likely due to Doppler measurement and inability to identify near-occlusions.
- Largest RCT of asymptomatic CEA: 3,120 patients, 1993-2003, international.
- Uncertainty Principle enrollment: very few exclusion criteria; enrolled when clinician genuinely uncertain.
- 12% had remote symptoms (>6 months prior) — not truly 100% asymptomatic.
- Medical arm 5-year event rate 11.8% — modest absolute benefit given elective surgery risk.
Study Design
- Study Type
- Randomized controlled trial, pragmatic design
- Randomization
- Yes
- Blinding
- Open-label (pragmatic)
- Sample Size
- 3120
- Follow-up
- 5 years (primary)
- Centers
- Multiple (international, predominantly European, UK-led)
- Countries
- United Kingdom and international
Primary Outcome
Definition: Any stroke or operative death at 5 years
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 11.8% | 6.5% | - (3.0% to 7.8%) | <0.05 |
Limitations & Criticisms
- Higher operative risks than ACAS, questioning generalizability of ACAS results
- No evaluation of ultrasonographer training or centralized audit of performance
- Less stringent surgeon selection compared to ACAS
- Unclear whether benefit exists at all in women
- Number needed to treat remains high (≥40) for disabling/fatal stroke prevention
- No prespecified subgroup analyses in trial protocol
Citation
Lancet. 2004;363:1491-1502