NASCET
PubMed • Full text • PDF
Clinical Question
In patients with symptomatic stenosis, does CEA reduce risk of death or stroke?
Bottom Line
CEA reduces the 5-year risk of death or stroke by 29% among patients with symptomatic high-moderate (50-69%) carotid stenosis.
Major Points
Prior studies had demonstrated the benefit of carotid endarterectomy (CEA) in patients with severe carotid stenosis, but NASCET was the first large, well-designed trial to study CEA in patients with low-moderate (<50%), high-moderate (50-69%), and severe (≥70%) stenosis. Those with symptomatic 50-69% stenosis had a 29% reduction in the 5-year risk of death or stroke, while those with <50% stenosis had no such benefit. Those with ≥70% stenosis received such a dramatic benefit that this study arm was prematurely stopped and all patients with severe stenosis were subsequently referred for CEA.
Guidelines
- The 2005 American Academy of Neurology guidelines[1] make the following recommendations:
- CEA if symptomatic in previous 6 months and 70-99% stenosis (level A)
- CEA consideration if symptomatic and 50-69% stenosis (level B)
- No consideration for CEA if symptomatic and <50% stenosis (level A)
Design
- Multicenter, parallel-group, randomized controlled trial
- N=2,226
- CEA (n=1,108)
- Medical therapy (n=1,108)
- Setting: 106 centers worldwide
- Enrollment: 1988-1991
- Mean follow up: 5 years
Population
Inclusion Criteria
- Symptomatic stenosis <70% in ipsilateral internal carotid artery imaged within 180 days
- TIA or nondisabling stroke (Rankin score <3) were considered symptoms of stenosis
- Stenosis assessed on selective angiography
- Minimum 2 projections showing cervical and intracranial carotid arteris and major branches
- Ipsilateral atheromatous stenosis must be >30%, <100%, and be technically suitable for CEA
- CT head, carotid doppler US, and CXR required
Exclusion Criteria
- Age >80 years (excluded in first phase only)
- Lack of angiographic evidence of ipsilateral stenosis
- Intracranial stenosis more clinically significant than cervical lesion
- Other lesion limiting life expectancy to <5 years
- Cerebral infarction eliminating useful function in affected vascular distribution
- Nonatherosclerotic carotid disease
- Carotid lesions likely to cause cardioembolism
- History of ipsilateral endarterectomy
Interventions
- Study divided into two phases
- First phase: moderate/severe stenosis
- Second phase: moderate stenosis alone
- Randomized to CEA or medical therapy
- Patients with moderate stenosis who progressed to severe stenosis were offered endarterectomy
- Patients received antiplatelet therapy (typically aspirin, dose adjusted to investigator) and antihypertensive and cholesterol-lowering drugs when indicated
- Surgical technique decided by individual surgeons, but simultaneous vascular procedures were discouraged
- Neurological follow up at 1, 3, 6, 9, and 12 months, then every 4 months
- Carotid doppler ultrasound performed at 1 month, annually, and after cerebrovascular events
Outcomes
Comparisons are CEA vs. medical management.
Primary Outcomes
- Ipsilateral stroke at 5 years
- With 50-69% stenosis
- 15.7% vs. 22.2% (RR 0.71; 95% CI 0.48-0.93; P=0.045), NNT=15
- With <50% stenosis
- 14.9% vs. 18.7% (P=0.16)
Secondary Outcomes
- Death or stroke at 30 days
- With 50-69% stenosis
- 33.2% vs. 43.3% (RR 0.77; P=0.005), NNT 10
- With <50% stenosis
- 36.2% vs. 37% (RR 0.98; P=0.97)
Subgroup Analysis
- Factors predicting perioperative stroke or death (P<0.05):
- Contralateral carotid occlusion
- Left-sided carotid disease
- Taking aspirin <650mg daily
- Absence of MI/angina
- CT or MR imaging evidence of ipsilateral cerebral infarction
- Diabetes
- Hypertension
- Factors predicting durability of CEA benefit (P<0.05):
- Male sex
- Recent stroke
- Recent hemispheric symptoms
- Taking aspirin ≥650mg daily
Funding
Funded by NINDS, with SmithKline Beechman providing aspirin.