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ACAS

Endarterectomy for Asymptomatic Carotid Artery Stenosis

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Year of Publication: 1995

Authors: Executive Committee for the Asymptomatic Carotid Atherosclerosis Study

Journal: JAMA

Citation: JAMA. 1995;273:1421-1428

Link: https://pubmed.ncbi.nlm.nih.gov/7723155

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?

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

Baseline Characteristics

CharacteristicOverall cohortControlActive
Mean age67 years
Mean weight81 kg (men), 67 kg (women)
Mean systolic BP146 mm Hg
Mean diastolic BP78 mm Hg
Mean total cholesterol5.90 mmol/L (228 mg/dL)
Prior myocardial infarction21%
Prior coronary artery bypass21%
Age 60-69 y46%50%
Age 70-79 y38%36%
Male sex66%66%
White race95%94%
Coronary artery disease69%69%
Hypertension64%64%
Diabetes mellitus21%25%
Current cigarette smoker24%28%
Ipsilateral bruit74%76%
Contralateral bruit42%44%
Infarct on CT (any location)24%22%
Contralateral occlusion by Doppler9%10%

Arms

FieldSurgical GroupControl
InterventionCarotid endarterectomy within 2 weeks of randomization plus daily aspirin (325 mg) and medical risk factor managementDaily aspirin (325 mg) and aggressive medical risk factor management including hypertension control, diabetes management, lipid control, smoking cessation
Duration5 years follow-up5 years follow-up

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Ipsilateral stroke and any perioperative stroke or death (5-year Kaplan-Meier estimate)Primary92 (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)Secondary102 observed; 160 (19.2%) at 5 y55 observed; 67 (8.2%) at 5 y<0.001
Major ipsilateral stroke or any perioperative major stroke or deathSecondary24 observed; 50 (6.0%) at 5 y21 observed; 28 (3.4%) at 5 y0.12
Any stroke or any perioperative deathSecondary86 observed; 146 (17.5%) at 5 y60 observed; 102 (12.4%) at 5 y0.09
Any major stroke or perioperative deathSecondary40 observed; 76 (9.1%) at 5 y28 observed; 53 (6.4%) at 5 y0.26
Any stroke or deathSecondary155 observed; 266 (31.9%) at 5 y127 observed; 211 (25.6%) at 5 y0.08
Any major stroke or deathSecondary213 (25.5%) at 5 y100 observed; 171 (20.7%) at 5 y0.16
Perioperative stroke or deathAdverse3 (0.4%)19 (2.3%)
Arteriographic complicationsAdverseNot 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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