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ACST

Medical Research Council Asymptomatic Carotid Surgery Trial

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Year of Publication: 2004

Authors: A. Halliday, A. Mansfield, J. Marro, ..., D. Thomas

Journal: Lancet

Citation: Lancet. 2004;363:1491-1502

Link: https://www.ahajournals.org/doi/10.1161/...141706.50170.a7

PDF: https://www.ahajournals.org/doi/pdf/10.1...141706.50170.a7

Clinical Question

Does immediate carotid endarterectomy plus medical treatment versus medical treatment alone reduce stroke risk in patients with asymptomatic carotid stenosis in a more pragmatic clinical setting?

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.

      

Design

Study Type: Randomized controlled trial, pragmatic design

Randomization: 1

Blinding: Open-label (pragmatic)

Enrollment Period: 1993-2003

Follow-up Duration: 5 years (primary)

Centers: Multiple (international, predominantly European, UK-led)

Countries: United Kingdom and international

Sample Size: 3120

Analysis: Intention-to-treat

Inclusion Criteria

Carotid stenosis >60% (Doppler ultrasonography).
Mainly asymptomatic (12% had symptoms >6 months prior).
Uncertainty Principle: enrolled when clinician genuinely uncertain about benefit of surgery.
Surgeon required evidence of ≤6% operative risk for last 50 asymptomatic CEA patients.

Exclusion Criteria

Very few exclusion criteria mentioned
Recent neurological symptoms (within 6 months for 12% of patients)

Baseline Characteristics

Characteristic	Control	Active
5-year stroke risk	11.8%
Stenosis assessment	Doppler ultrasonography	Doppler ultrasonography
No centralized audit	of ultrasonographer performance
Required operative risk		≤6% for last 50 asymptomatic CEA patients
Surgeon exclusions		None based on operative risk during trial

Arms

Field	Immediate Surgery Group	Control
Intervention	Immediate carotid endarterectomy plus medical treatment	Medical treatment alone or until operation became necessary (delayed surgery)
Duration	5 years follow-up	5 years follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Any stroke or operative death at 5 years	Primary	11.8%	6.5%	5.30%	<0.05
Disabling or fatal stroke	Secondary	Not specified	2.5% absolute reduction		0.004
30-day operative mortality	Secondary	0%	1.11% (95% CI 0.6% to 1.8%)		0.02 vs ACAS
30-day stroke and death	Secondary	0%	3.0% (95% CI 2.1% to 4.0%)		0.04 vs ACAS
Perioperative stroke/death	Adverse	Not applicable	3.0% (vs 1.5% in ACAS)		0.04
Perioperative death	Adverse	Not applicable	1.11% (vs 0.14% in ACAS)		0.02

Subgroup Analysis

Surgical benefit greater in men than women across both ACST and ACAS (pooled interaction P=0.01). Benefit in women remains uncertain.

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

Funding

Medical Research Council (UK)

Based on: ACST (Lancet, 2004)