ACAS
Endarterectomy for Asymptomatic Carotid Artery Stenosis
Clinical Question
Will carotid endarterectomy added to aggressive reduction of modifiable risk factors and administration of aspirin reduce the 5-year risk of ipsilateral cerebral infarction in individuals with asymptomatic hemodynamically significant carotid artery stenosis?
Study Overview
Objective
To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis
Study Summary
- Carotid endarterectomy reduced 5-year ipsilateral stroke risk by 53% (5.1% vs 11.0%)
- Absolute risk reduction of 5.9% with perioperative mortality/morbidity of 2.3%
- Number needed to treat: 17 patients to prevent one stroke over 5 years
Intervention
Carotid endarterectomy plus daily aspirin (325 mg) and medical risk factor management versus medical management alone
Patients per Arm
1662 randomized (825 surgical, 834 medical); follow-up data available on 1659
Bottom Line
Patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter and whose general health makes them good candidates for elective surgery will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors
Major Points
- Prospective, randomized, multicenter trial; 1662 patients randomized and 1659 analyzed (825 surgical, 834 medical) with asymptomatic carotid stenosis ≥60%
- Median follow-up of 2.7 years with 4657 patient-years of observation
- 53% relative risk reduction in ipsilateral stroke and perioperative stroke/death (5.1% vs 11.0%)
- Absolute 5-year risk reduction of 5.9%, number needed to treat of 17
- Perioperative stroke/death rate of 2.3% in surgical group vs 0.4% in medical group
- Trial stopped early after eighth interim analysis due to efficacy
Design
Study Type: Randomized controlled trial
Randomization: 1
Blinding: Masked outcome assessment with blinded adjudication committee for end points
Enrollment Period: December 1987 to December 1993
Follow-up Duration: Median 2.7 years
Centers: 39
Countries: United States, Canada
Sample Size: 1659
Analysis: Intention-to-treat analysis using Kaplan-Meier estimates with large-sample tests, modified O'Brien-Fleming stopping rule
Inclusion Criteria
- Age between 40 and 79 years
- Asymptomatic carotid artery stenosis ≥60% diameter reduction
- Compatible history and findings on physical and neurological examinations
- Performance of required laboratory and electrocardiographic examinations no earlier than 3 months before randomization
- Patient accessibility and willingness to be followed for 5 years
- Valid informed consent
Exclusion Criteria
- Cerebrovascular events in distribution of study carotid artery or vertebrobasilar system
- Symptoms referable to contralateral cerebral hemisphere within previous 45 days
- Contraindication to aspirin therapy
- Disorder that could seriously complicate surgery
- Condition that could prevent continuing participation or was likely to produce disability or death within 5 years
Arms
| Field | Surgical Group | Control |
|---|---|---|
| Intervention | Carotid endarterectomy within 2 weeks of randomization plus daily aspirin (325 mg) and medical risk factor management | Daily aspirin (325 mg) and aggressive medical risk factor management including hypertension control, diabetes management, lipid control, smoking cessation |
| Duration | 5 years follow-up | 5 years follow-up |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Ipsilateral stroke and any perioperative stroke or death (5-year Kaplan-Meier estimate) | Primary | 92 (11.0%) | 42 (5.1%) | 5.9% | 0.004 |
| Ipsilateral TIA or stroke or any perioperative TIA, stroke, or death (original primary endpoint prior to March 1993) | Secondary | 102 observed; 160 (19.2%) at 5 y | 55 observed; 67 (8.2%) at 5 y | <0.001 | |
| Major ipsilateral stroke or any perioperative major stroke or death | Secondary | 24 observed; 50 (6.0%) at 5 y | 21 observed; 28 (3.4%) at 5 y | 0.12 | |
| Any stroke or any perioperative death | Secondary | 86 observed; 146 (17.5%) at 5 y | 60 observed; 102 (12.4%) at 5 y | 0.09 | |
| Any major stroke or perioperative death | Secondary | 40 observed; 76 (9.1%) at 5 y | 28 observed; 53 (6.4%) at 5 y | 0.26 | |
| Any stroke or death | Secondary | 155 observed; 266 (31.9%) at 5 y | 127 observed; 211 (25.6%) at 5 y | 0.08 | |
| Any major stroke or death | Secondary | 213 (25.5%) at 5 y | 100 observed; 171 (20.7%) at 5 y | 0.16 | |
| Perioperative stroke or death | Adverse | 3 (0.4%) | 19 (2.3%) | ||
| Arteriographic complications | Adverse | Not applicable (medical arm did not undergo protocol arteriography) | 5 of 414 surgical patients undergoing pre-CEA arteriography (1.2%) |
Subgroup Analysis
Men showed 66% risk reduction (95% CI 36% to 82%) while women showed 17% reduction (95% CI -96% to 65%), but difference not statistically significant (P=0.10)
Criticisms
- Only ~4% of screened patients (1662 of >42,000) were randomized, limiting generalizability
- Higher perioperative complication rate in women (3.6% vs 1.7% in men)
- Trial stopped early based on interim analysis
- Median follow-up only 2.7 years with limited 5-year data
- All surgical patients required arteriography with additional 1.2% stroke risk
- Results may not apply to centers with higher perioperative complication rates
Funding
Investigator-initiated research grant (RO1 NS22611) from the US Public Health Service National Institute of Neurological Disorders and Stroke
Based on: ACAS (JAMA, 1995)
Authors: Executive Committee for the Asymptomatic Carotid Atherosclerosis Study
Citation: JAMA. 1995;273:1421-1428
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