CREST
Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis
Clinical Question
Does carotid-artery stenting differ from carotid endarterectomy in the composite outcome of stroke, MI, or death in patients with symptomatic or asymptomatic carotid stenosis?
Study Overview
Objective
Carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in symptomatic and asymptomatic carotid artery stenosis.
Study Summary
- Risk of stroke, MI, or death did not differ between CAS and CEA groups in patients with symptomatic or asymptomatic carotid stenosis.
- During the periprocedural period, the risk of stroke was higher in the CAS group, while the risk of MI was higher in the CEA group.
- After the periprocedural period, stroke risk was similar between groups.
Intervention
Carotid artery stenting (CAS) vs. carotid endarterectomy (CEA).
Patients per Arm
2522 randomized (1271 CAS, 1251 CEA); 2502 analyzed (1262 CAS, 1240 CEA)
Bottom Line
Carotid-artery stenting and endarterectomy had similar rates of the composite endpoint, but stenting had higher periprocedural stroke risk and lower MI risk. Age influenced relative outcomes with a crossover at approximately 70 years.
Major Points
- Largest randomized comparison of carotid artery stenting (CAS) vs carotid endarterectomy (CEA). 2,522 patients randomized (2,502 analyzed) with symptomatic or asymptomatic carotid disease at 117 U.S./Canadian centers.
- Mixed population: 53% symptomatic and 47% asymptomatic patients — a key design feature.
- Primary composite endpoint (periprocedural stroke, MI, or death OR ipsilateral stroke within 4 years): 7.2% CAS vs 6.8% CEA (HR 1.11, 95% CI 0.81–1.51, P=0.51) — no significant difference. Analyses were aimed at testing for superiority.
- Periprocedural stroke was higher with CAS: 4.1% vs 2.3% (P=0.01). Periprocedural MI was higher with CEA: 2.3% vs 1.1% (P=0.03). Cranial nerve palsy: 0.3% CAS vs 4.7% CEA.
- Age interaction with treatment efficacy (P=0.02): carotid-artery stenting tended to show greater efficacy at younger ages, and carotid endarterectomy at older ages, with a crossover at approximately 70 years (per-age hazard ratios shown graphically in Figure 2B; specific numeric HRs at ages <70 or ≥70 were not reported in the primary paper).
- Devices: RX Acculink nitinol stent + Accunet embolic protection device (Abbott Vascular). Operators (477 surgeons, 224 interventionists) were credentialed and completed a lead-in phase of training; no specific case-number or complication-rate threshold for interventionists is stated in the primary paper.
- CREST-2 (ongoing) is testing CAS vs intensive medical management alone and CEA vs intensive medical management alone for asymptomatic carotid stenosis.
- The primary paper reports median follow-up of 2.5 years (up to 4 years); longer-term outcomes were noted as being assessed out to 10 years but are not reported in the primary paper.
Design
Study Type: Randomized, controlled, open-label, blinded-endpoint trial
Randomization: 1
Blinding: Blinded endpoint adjudication
Enrollment Period: December 2000 – July 2008
Follow-up Duration: Median 2.5 years (up to 4 years)
Centers: 117
Countries: USA, Canada
Sample Size: 2502
Analysis: Intention-to-treat, Kaplan-Meier, proportional hazards modeling with subgroup analyses; testing for superiority
Inclusion Criteria
- Symptomatic patients: TIA, amaurosis fugax, or minor nondisabling stroke involving the study carotid artery within 180 days before randomization
- Symptomatic stenosis: ≥50% on angiography, ≥70% on ultrasound, or 50–69% on ultrasound with CTA/MRA showing ≥70%
- Asymptomatic (added 2005): ≥60% on angiography, ≥70% on ultrasound, or 50–69% on ultrasound with CTA/MRA showing ≥80%
- Clinical and anatomical suitability for either revascularization technique
Exclusion Criteria
- Previous stroke sufficiently severe to confound endpoint assessment
- Myocardial infarction within the previous 30 days, or unstable angina
- Chronic atrial fibrillation, or paroxysmal atrial fibrillation within the preceding 6 months or requiring anticoagulation therapy
Arms
| Field | Carotid Artery Stenting (CAS) | Control |
|---|---|---|
| Intervention | Carotid artery stenting with the RX Acculink nitinol self-expanding stent and Accunet embolic protection device (Abbott Vascular). Pre-procedure (≥48 hours before): aspirin 325 mg twice daily and clopidogrel 75 mg twice daily; if procedure scheduled <48 hours after randomization, 650 mg aspirin and 450 mg clopidogrel ≥4 hours before procedure. During procedure: heparin (86.4%) or bivalirudin (13.6%); embolic protection used in 96.1%. Post-procedure: one or two 325-mg doses of aspirin daily for 30 days plus clopidogrel 75 mg daily (or ticlopidine 250 mg twice daily) for 4 weeks; continuation of antiplatelet therapy beyond 4 weeks was recommended. Interventionists were credentialed and had participated in a lead-in phase of training (primary paper does not specify numeric case or complication-rate thresholds). | Standard carotid endarterectomy per published guidelines. General anesthesia used in 90.0%; surgical technique (patch 62.4%, shunt 56.7%) at operator discretion. Aspirin 325 mg daily started at least 48 hours before endarterectomy and continued for a year or more. Surgeons were selected via a validated process documenting performance of more than 12 procedures per year with rates of complications and death less than 3% among asymptomatic patients and less than 5% among symptomatic patients. |
| Duration | Up to 4 years | Up to 4 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Any stroke, myocardial infarction, or death during the periprocedural period, or ipsilateral stroke within 4 years after randomization | Primary | 6.8% | 7.2% | 1.11 | 0.51 |
| Periprocedural stroke (any) | Secondary | 2.3% | 4.1% | HR 1.79 (1.14–2.82) | 0.01 |
| Periprocedural myocardial infarction | Secondary | 2.3% | 1.1% | HR 0.50 (0.26–0.94) | 0.03 |
| Periprocedural death | Secondary | 0.3% | 0.7% | HR 2.25 (0.69–7.30) | 0.18 |
| 4-year stroke or death (all patients) | Secondary | 4.7% | 6.4% | HR 1.50 (1.05–2.15) | 0.03 |
| Post-periprocedural ipsilateral stroke | Secondary | 2.4% | 2.0% | 0.85 | |
| Any periprocedural stroke (CAS higher) | Adverse | 2.3% | 4.1% | HR 1.79 (1.14–2.82) | 0.01 |
| Periprocedural MI (CEA higher) | Adverse | 2.3% | 1.1% | HR 0.50 (0.26–0.94) | 0.03 |
| Cranial nerve palsy (periprocedural) | Adverse | 4.7% | 0.3% | HR 0.07 (0.02–0.18) | |
| Major ipsilateral stroke (periprocedural) | Adverse | 0.3% | 0.9% | HR 2.67 (0.85–8.40) | 0.09 |
Subgroup Analysis
Age (P=0.02 for interaction): carotid-artery stenting tended to show greater efficacy at younger ages and carotid endarterectomy at older ages, with a crossover at approximately 70 years (per-age hazard ratios shown graphically in Figure 2B; specific numeric HRs for <70 vs ≥70 not reported in primary paper). No significant interaction by sex (P=0.34) or symptomatic status (P=0.84). Symptomatic patients — primary endpoint periprocedural: 6.7% CAS vs 5.4% CEA (HR 1.26, 95% CI 0.81–1.96); 4-year 8.6% CAS vs 8.4% CEA (HR 1.08, 95% CI 0.74–1.59). Asymptomatic patients — primary endpoint periprocedural: 3.5% CAS vs 3.6% CEA (HR 1.02, 95% CI 0.55–1.86); 4-year 5.6% CAS vs 4.9% CEA (HR 1.17, 95% CI 0.69–1.98). Post hoc analyses suggested periprocedural stroke had greater impact on 1-year quality of life (SF-36) than periprocedural MI.
Criticisms
- Single stent system (RX Acculink + Accunet) — newer-generation stents with mesh protection may have different outcomes.
- Highly credentialed operators with lead-in phase — community results may differ, especially for CAS.
- Mixed symptomatic/asymptomatic cohort (53%/47%) dilutes power for each subgroup.
- No medical therapy-only comparator arm (being addressed by CREST-2).
- Inclusion of MI in the composite endpoint is debated — strokes had greater impact on quality of life than MIs in post hoc analyses.
- Long enrollment period (2000–2008) during which medical therapy and stent technology evolved.
- Age interaction (P=0.02) is a key finding but was based on a continuous interaction test — the ~70-year cutoff is approximate.
- Primary paper reports outcomes through median 2.5 years (up to 4 years); longer-term data are not included in this report.
Funding
National Institute of Neurological Disorders and Stroke (NINDS/NIH; R01 NS 038384) with supplemental funding from Abbott Vascular Solutions (formerly Guidant), including donations of Accunet and Acculink systems equivalent to approximately 15% of the total study cost.
Based on: CREST (New England Journal of Medicine, 2010)
Authors: Brott TG, Hobson RW, Howard G, ..., Meschia JF
Citation: N Engl J Med 2010; 363:11–23. doi:10.1056/NEJMoa0912321
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