• Acas Carotid Study Questions
• Acas Carotid Study Meaning
• Endarterectomy Vs Stenting

Description:

Carotid endarterectomy for 5-year ipsilateral stroke in asymptomatic patients.

In 1995 the Asymptomatic Carotid Atherosclerosis Study (ACAS) demonstrated that patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter benefited from endarterectomy, having a reduced 5-year risk of ipsilateral stroke 4.

The Asymptomatic Carotid Atherosclerosis Study Group. Study design for randomized prospective trial of carotid endarterectomy for asymptomatic atherosclerosis. Stroke 1989;20: 844 - 849. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. 1995; 273(18):1421-8 (ISSN: 0098-7484) 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. For asymptomatic carotid stenosis, ACAS (Asymptomatic Carotid Atherosclerosis Study) and ACST-1 (Asymptomatic Carotid Surgery Trial) established the benefit of CEA over medical therapy alone in patients with 60%–99% carotid stenosis.38 39 However, both studies started before the era of modern OMT, the widespread use of which has reduced the. The Asymptomatic Carotid Atherosclerosis Study (ACAS) established that the long-term risk of ipsilateral stroke in neurologically asymptomatic patients with a $60% carotid stenosis was reduced by carotid endarterectomy. The 5-year estimated risk for ipsilateral stroke was 11.0% and 5.1% for the medical and surgical groups, respectively, ie, a.

Hypothesis:

Carotid endarterectomy, added to aggressive reduction of modifiable risk factors and administration of aspirin would reduce the 5-year risk of ipsilateral cerebral infarction in individuals with asymptomatic, hemodynamically significant carotid artery stenosis.

Study Design

Study Design:

Patients Screened: 42,000
Patients Enrolled: 1,662
NYHA Class: Not given
Mean Follow Up: 2.7 years
Mean Patient Age: 67
Female: 36
Mean Ejection Fraction: Not given

Patient Populations:

> 40 and < 79 years of age
Compatible history and findings on physical and neurological examinations
Unilateral or bilateral surgically accessible stenosis of the common or internal carotid artery of at least 60% by arteriography; Doppler exam with velocity greater than instrument-specific cut point with 95% PPV; or Doppler exam with velocity greater than instrument-specific cut point with 90% PPV confirmed by ocular pneumoplethysmographic exam.
Accessibility and willingness to be followed for 5 years
Informed consent.

Exclusions:

Cerebrovascular events in the study artery distribution or in the vertebrobasilar arterial system
Symptoms referable to the contralateral cerebral hemisphere within preceding 45 days
Contraindication to aspirin therapy
Disorders that would seriously complicate surgery
Condition that would prevent continuing participation or likely to produce disability or death within 5 years.

Primary Endpoints:

In March 1993, the primary outcome measures were changed to cerebral infarction in the distribution of the study artery or any stroke or death occurring in the perioperative period.
Initially defined as TIA or infarction in the distribution of the study artery and any TIA, stroke, or death in the perioperative period.

Secondary Endpoints:

Any stroke and perioperative death
Any stroke and any death
Any ipsilateral TIA or stroke
Any perioperative TIA, stroke, or death.

Drug/Procedures Used:

Carotid endarterectomy.

Concomitant Medications:

Aspirin, 325 mg qd (all patients).

Acas Carotid Study Questions

Principal Findings:

Lower Kaplan-Meier estimated 5-year risk of ipsilateral stroke and any perioperative stroke or death for the surgical group (5.1%) vs medical therapy (11.0%). The reduction in 5-year ipsilateral stroke risk in the surgical group was 53% of the estimated 5-year risk in the medical group (95% CI, 22% to 72%), p = 0.004.
For the primary endpoint of ipsilateral stroke and any perioperative stroke or death, the survival curves cross near 10 months and become significantly reduced in the surgical group by 3 years (p < 0.05).
The original primary endpoint (ipsilateral TIA or stroke or any perioperative TIA, stroke or death) showed a 57% reduction in 5-year risk for the surgery group (95% CI, 39% to 70%).
The surgical group had a 20% reduction in any stroke or death compared to medical therapy, which was not statistically significant (95% CI -2% to 37%).
Subgroup analysis by gender showed no statistically significant difference between genders, although the 5-year event rate reduction was greater for men (66%, 95% CI, 36% to 82%) than for women (17%, 95% CI, -96% to 65%).
Silent infarction among the ACAS patients is not uncommon, but rarely sizable, and of unknown clinical significance.
In cost-effectiveness analyses, surgical treatment improved quality-adjusted life expectancy from 7.82 to 8.12 QUALYs, at an incremental lifetime cost of $2041. This yielded an incremental cost-effectiveness ratio of $8,000 per QUALY saved by surgical compared to medical treatment. Carotid endarterectomy was cost-effective for the ACAS population; however, it did not appear to be cost-effective for very elderly patients, in settings of high operative stroke risk, or in patients with very low stroke risk without surgery.

Interpretation:

The NASCET and ECST trials have shown benefit for symptomatic patients from carotid endarterectomy. ACAS demonstrated that the incidence of cerebral infarction can be reduced by endarterectomy, and forms the foundation for current clinical guidelines for asymptomatic patients. Four other randomized prospective studies of carotid endarterectomy for asymptomatic carotid artery stenosis have been reported. One did not include stenosis exceeding 90% [CASSANOVA, Stroke 1991; 22:1229-1235], another was terminated early because of excess cardiac events [Mayo Clin Proc 1992; 67:513-8]. The European Asymptomatic Carotid Surgery Trial is ongoing [ Eur J Vasc Surg 1994; 8:703-10]. The Veterans Affairs Cooperative trial of 444 men published results based on a mean follow-up of 47.9 months [N Engl J Med 1993; 328:221-7]. Following publication of ACAS, endarterectomy rates have dramatically increased in Florida [Stroke 1998; 29:1099-105] and in the Veterans Administration hospital system [Archives of Surgery 1997; 132:1134-9.]

References:

1. Stroke 1989; 20: 844-849 Study design and organization
2. Stroke 1994; 25: 1122-1129 Baseline silent cerebral infarction
3. JAMA 1995; 273:1421-8 Primary results
4. J Vasc Surg 1996; 23:323-8 Surgeon selection process
5. Stroke 1996; 27:1951-7 Doppler ultrasound as screening tool
4. Stroke 1997; 28:1648 Perioperative surgical morbidity and mortality
5. Neurology 1997; 48:346-51 Validation of ACAS TIA/stroke algorithm
6. J Vasc Surg 1997; 25:298-309 Cost-effectiveness analysis

Clinical Topics:Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Interventions and Vascular Medicine

Keywords:Stroke, Platelet Aggregation Inhibitors, Endarterectomy, Carotid, Life Expectancy, Constriction, Pathologic, United States Department of Veterans Affairs, Carotid Artery, Internal, Neurologic Examination, Cerebral Infarction, Florida, Carotid Stenosis, Informed Consent

• 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

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%

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

Acas Carotid Study Meaning

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)

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)

Endarterectomy Vs Stenting

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.

Further Reading