Acas Carotid Trial

1. Acas Carotid Trial Meaning
2. Acas Carotid Trial
3. Acas Carotid Trial Procedure
4. Acas Carotid Trial Hearing

Purpose: Proponents of carotid angioplasty and stenting suggest that “high risk” patients, defined as patients excluded from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Asymptomatic Carotid Atherosclerosis Study (ACAS), may have a significantly higher risk of stroke with carotid endarterectomy (CEA). THE NASCET 1 and the ACAS 2 were the largest and best-organized trials affecting the management of extracranial carotid arteriosclerosis. Both trials have clearly defined patient populations that benefit from carotid endarterectomy compared with best medical management.

• 6Population
• 8Outcomes

Clinical Question

Does carotid endarterectomy (CEA) and aggressive medical therapy reduce incidence of cerebral infarction over 5 years in patients with asymptomatic carotid artery stenosis?

Bottom Line

Patients with asymptomatic carotid artery stenosis of 60% or greater who are good surgical candidates have reduced 5-year risk of ipsilateral stroke.

Major Points

While the NASCET trial showed the benefit of CEA for patients symptomatic from carotid artery stenosis, the Asymptomatic Carotid Atherosclerosis Study (ACAS) trial sought to test whether a morbidity and mortality benefit existed for treated asymptomatic patients with CEA. ACAS demonstrated that asymptomatic patients with carotid artery stenosis >60% who undergo CEA have a lower chance of a combined endpoint of ipsilateral stroke, or perioperative stroke or death over 5 years.

Guidelines

No guidelines have been published that reflect the results of this trial.

Design

• 39 center trial
• Non-blinded
• Randomized
• N=1,662
  • Aggressive Medical Therapy alone (n=834)
  • Aggressive Medical Therapy + Carotid Endarterectomy (n=825)
• Enrollment: December 1987 to December 1993.
• Median follow-up: 2.7 years
• Analysis: Intention-to-treat

Population

Inclusion Criteria

• Aged 40-79
• Compatible history and findings on physical and neurological exams
• Performance of required lab and ECG testings no earlier than 3 months prior to randomization
• Patient accessibility and willingness to be followed for 5 years
• Valid informed consent

Acas Carotid Trial Meaning

Exclusion Criteria

• Cerebrovascular events in the distribution of the study carotid artery
• Cerebrovascular events in the distribution of the vertebrobasilar arterial system
• Symptoms referable to the contralateral hemisphere within the previous 45 days
• Contraindications to aspirin
• Disorder that seriously complicate surgery
• Condition that would prevent continuing participation, or that would likely produce disability or death within 5 years)

Baseline Characteristics

• Gender: Approximately 2 Male:1 Female
• Age
  • 40-49: ~2%
  • 50-59: ~14%
  • 60-69: ~48%
  • 70-79: ~37%
• Percent Stenosis
  • 0-59%: NA
  • 60-69%: ~36%
  • 70-79%: ~37%
  • 80-80%: ~25%
  • 90-99%: ~5%

Acas Carotid Trial

Interventions

• 'Aggressive Medical Therapy': 325mg of regular or enteric-coated aspiring daily and 'modification of stroke risk factors'
• 'Aggressive Medical Therapy' Plus Carotid Endarterectomy

Outcomes

Comparisons are Medical versus Surgery

Primary Outcomes

Ipsilateral Stroke or any perioperative stroke or death

11.0% v 5.1% (p=0.004)

Secondary Outcomes

Major Ipsilateral Stroke or any perioperative major stroke or death

6.0% v 3.4% (p=0.12)

Ipsilateral TIA or Stroke or any perioperative TIA or stroke or death

19.2% v 8.2% (p<0.001)

Any stroke or any perioperative death)

17.5% v 12.4% (p=0.09)

Any major stroke or perioperative death

9.1% v 6.4% (p=0.26)

Any stroke or death

31.9% v 25.6% (p=0.08)

Any major stroke or death

25.5% v 20.7% (p=0.16)

Subgroup Analysis

Reduction due to Surgery in 5 year risk as a proportion of risk in the medical group

By Sex

Men: 0.66 (95% CI: 0.36 to 0.82)

Women: 0.17 (95% CI: -0.96 to 0.65)

By Age

< 68 y.o.: 0.60 (95% CI: 0.11 to 0.82)

>= 68 y.o.: 0.43 (95% CI: -0.07 to 0.70)

Acas Carotid Trial Procedure

By history

Bilaterally asymptomatic: 0.46 (95% CI: 0.00 to 0.71)

Previous Contralateral endarterectomy or previous TIA or stroke: 0.65 (95% CI: 0.13 to 0.86)

Protocol adherence

Patients receiving assigned treatment: 0.55 (95% CI: 0.23 to 0.74)

By degree of Stenosis

60-69.9%: 0.45 (95% CI: -0.70 to 0.82)

70-79.9%: 0.67 (95% CI: -0.65 to 0.94)

80-99.9%: 0.45 (95% CI: -2.19 to 0.91)

Criticisms

• This study relied heavily on composite endpoints for all endpoints, which may not be statistically rigorous.
• 'Aggressive Medical Therapy' in 1995 consisted on aspirin alone, whereas modern clinical guidelines demand treating patients with atherosclerotic disease with a statin. Additionally, modern medical therapy includes management of comorbidities such as hypertension and diabetes mellitus, but newer medications have improved efficacy, which may affect how effective medical management can be.

Funding

• This study was funded by the National Institutes of Neurological Disorders and Stroke, NIH.
• A conflict of interest may exist because the study was examining the clinical effectiveness of a surgical intervention by vascular surgeons, when these very physicians are those whose careers will suffer if CEA proved to be inferior.

Acas Carotid Trial Hearing

Further Reading