CREST
(2010)Objective
Carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in symptomatic and asymptomatic carotid artery stenosis.
Study Summary
Intervention
Carotid artery stenting (CAS) vs. carotid endarterectomy (CEA).
Inclusion Criteria
Patients with symptomatic (TIA, minor stroke, or amaurosis fugax in prior 180 days) or asymptomatic carotid stenosis. Symptomatic stenosis: ≥50% on angiography, 70% on ultrasound, or 50-69% on ultrasound with CTA/MRA showing ≥70%. Asymptomatic stenosis: ≥60% on angiography, 70% on ultrasound, or 50-69% on ultrasound with CTA/MRA showing ≥80%.
Study Design
Arms: CAS vs. CEA
Patients per Arm: 2502 total patients (split between CAS and CEA)
Outcome
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.
Major Points
- Largest randomized comparison of carotid artery stenting (CAS) vs carotid endarterectomy (CEA). 2,502 patients with symptomatic (≥50% stenosis, TIA/stroke within 180 days) or asymptomatic (≥60% stenosis) carotid disease at 117 U.S./Canadian centers.
- Composite of 47% symptomatic and 53% asymptomatic patients — mixed population is a key design feature.
- Primary composite endpoint (stroke, MI, or death periprocedurally 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.
- 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.
- Critical age interaction (P=0.02): CAS favored in patients <70 years (HR 0.69), CEA favored in patients ≥70 years (HR 1.66). Crossover age was ~70 years.
- Devices: RX Acculink nitinol stent + Accunet embolic protection device (Abbott Vascular). Operators required lead-in phase of ≥10 cases with ≤6% complication rate.
- CREST-2 (ongoing) is testing CAS vs intensive medical management alone (without CEA comparator) and CEA vs intensive medical management alone for asymptomatic carotid stenosis.
- Long-term follow-up (10 years, published 2016): composite endpoint remained similar. Restenosis was higher after CAS (6.0% vs 3.3%) but did not translate to more ipsilateral strokes.
Study Design
- Study Type
- Randomized, controlled, open-label, blinded-endpoint trial
- Randomization
- Yes
- Blinding
- Blinded endpoint adjudication
- Sample Size
- 2502
- Follow-up
- Median 2.5 years (up to 4 years)
- Centers
- 117
- Countries
- USA, Canada
Primary Outcome
Definition: Any stroke, MI, or death during the periprocedural period or ipsilateral stroke within 4 years
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 6.8% | 7.2% | 1.11 (0.81–1.51) | 0.51 |
Limitations & Criticisms
- Single stent system (RX Acculink + Accunet) — newer-generation stents with mesh protection (CGuard, GORE Flow Reversal) may have better outcomes.
- Highly credentialed operators with lead-in phase — community results may be worse, especially for CAS.
- Mixed symptomatic/asymptomatic cohort (47%/53%) dilutes power for each subgroup — cannot draw firm conclusions for either group alone.
- No medical therapy-only comparator arm — cannot assess whether either procedure is superior to optimal medical therapy alone (being addressed by CREST-2).
- Inclusion of MI in the composite endpoint is controversial — strokes had greater impact on quality of life than MIs in post hoc analyses.
- Long enrollment period (2000–2008) — medical therapy and stent technology evolved significantly during this time.
- Age interaction (P=0.02) is the key finding but was based on a continuous interaction test — the 70-year cutoff is approximate.
Citation
N Engl J Med 2010; 363:11–23. doi:10.1056/NEJMoa0912321