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Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis - EVA-3S
Description:
The goal of the trial was to evaluate whether carotid artery stenting (CAS) was noninferior to carotid endarterectomy (CEA) among patients with symptomatic carotid artery stenosis.
Hypothesis:
CAS will be noninferior to CEA.
Study Design
Patients Screened: 527
Patients Enrolled: 527
Mean Follow Up: 7.1 years
Mean Patient Age: 70 years
Female: 25%
Patient Populations:
- Age ≥18 years
- Hemispheric or retinal transient ischemic attack or a nondisabling stroke (or retinal infarct) within 120 days prior to enrollment
- Stenosis of 60%-99% in the symptomatic carotid artery
Exclusions:
- Modified Rankin score of ≥3; nonatherosclerotic carotid disease
- Severe tandem lesions
- Previous revascularization of the symptomatic stenosis
- History of bleeding disorder
- Uncontrolled hypertension or diabetes
- Unstable angina
- Contraindication to heparin, ticlopidine, or clopidogrel
- Life expectancy <2 years
- Percutaneous or surgical intervention within 30 days before or after the study procedure
Primary Endpoints:
Any stroke or death within 30 days of treatment
Secondary Endpoints:
- Myocardial infarction
- Transient ischemic attack
- Cranial-nerve injury
- Major local complications
- Systemic complications within 30 days after treatment
- Composites of any stroke or death within 30 days after treatment plus ipsilateral stroke, any stroke, or any stroke or death within 31 days through 4 years of follow-up
Drug/Procedures Used:
Patients with symptomatic carotid artery stenosis of ≥60% were randomized to CAS (n = 265) or CEA (n = 262). The trial, conducted in 30 centers in France, was publicly funded and not sponsored by a device company. To avoid using sites without experience, the trial required that a minimum number of cases had been performed by both the surgeon and the interventionalist in order to participate in the trial. Following an amendment, stents with cerebral protection devices were to be used.
Concomitant Medications:
At 4 years, for CAS vs. CEA, the use of an antiplatelet agent was 99% vs. 95%, an antihypertensive agent was 87% vs. 86%, and the use of lipid-lowering medication was 82% vs. 83%.
Principal Findings:
The trial was stopped early after an increased hazard was observed with CAS vs. CEA. The primary composite endpoint of death or stroke was more than double in the CAS group compared with the CEA group (9.6% vs. 3.9%, relative risk [RR] 2.5, 95% confidence interval [CI] 1.2-5.1, p = 0.01). Even after the amendment regarding use of stenting with cerebral protection (n = 277), death or stroke was higher with CAS compared with CEA (RR 3.4, 95% CI 1.1-10.0).
Results were similar regardless of physician experience or center volume. Nonfatal stroke was significantly higher in the CAS group (8.8% vs. 2.7%, RR 3.3, 95% CI 1.4-7.5, p = 0.004), including disabling stroke (2.7% vs. 0.4%) and non-disabling stroke (6.1% vs. 2.3%). Mortality did not differ between the groups (0.8% vs. 1.2%, p = 0.68). Bradycardia or hypotension occurred more frequently within the stenting group (4.2% vs. 0%, p < 0.001). Nerve injury was more common in the CEA group (7.7% vs. 1.1%, p < 0.001). At 6 months, the composite of death or stroke remained higher in the stenting group (11.7% vs. 6.1%, p = 0.02).
Type of stent used was Carotid Wallstent Monorail (56.9%), Acculink (28.5%), and Precise RX (10.6%). Cerebral protection was used in 92% of CAS patients.
At 4 years, death or any stroke had occurred in 26.9% of the CAS group vs. 21.6% of the CEA group (p = 0.08), and any ipsilateral stroke had occurred in 11.1% of the CAS group vs. 6.2% of the CEA group (p = 0.03).
The cumulative probability of any ipsilateral stroke or procedural stroke/death at 5 years occurred in 11.0% of the CAS group vs. 6.3% of the CEA group (p = 0.04), whereas the cumulative probability of any ipsilateral stroke or procedural stroke/death at 10 years occurred in 11.5% of the CAS group vs. 7.6% of the CEA group (p = 0.07).
Postprocedural ipsilateral strokes from day 31 to the end of follow-up occurred in six CAS patients vs. eight CEA patients (p = 0.67).
Interpretation:
Among patients with symptomatic carotid artery stenosis, treatment with CAS was associated with a 2.5 times higher rate of death or stroke by 30 days compared with CEA. For every 17 patients treated with stenting rather than endarterectomy, one additional stroke or death occurred. Use of distal protection devices did not appear to alter the early results of the increased hazard with stenting. This hazard was minimized in long-term follow-up.
At 5 years of follow-up, there was an excess of any ipsilateral stroke or procedural stroke/death with CAS vs. CEA. At 10 years, adverse events were still numerically higher with CAS; however, the difference was nonsignificant. Postprocedural ipsilateral strokes were infrequent and occurred at a similar frequency between groups.
The present trial adds to the body of evidence examining the long-term safety of carotid stenting for symptomatic carotid artery stenosis. The recent SPACE trial failed to show that carotid stenting was noninferior to endarterectomy at 30 days, although outcomes were similar by 2 years.
Carotid stenting for treatment of symptomatic carotid artery stenosis was approved by the Food and Drug Administration based mainly on data from the SAPPHIRE trial, the only randomized trial to show noninferiority of carotid stenting compared with endarterectomy. Approximately 30% of the patients in SAPPHIRE were symptomatic and there was no benefit of stenting compared with endarterectomy in this patient subgroup. Since then, large randomized trials have failed to show noninferiority or have shown an increased hazard with carotid stenting in symptomatic patients with early follow-up. With long-term follow-up, the difference between these treatment modalities appears to be minimized.
References:
Mas JL, Arquizan C, Calvet D, et al., on behalf of the EVA-3S Investigators. Long-term follow-up study of endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis trial. Stroke 2014;Jul 31:[Epub ahead of print].
Mas JL, Trinquart L, Leys D, et al. Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial. Lancet Neurol 2008;Sep 5:[Epub ahead of print].
Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006;355:1660-71.
Keywords: Risk, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Endarterectomy, Carotid, Hypotension, Carotid Arteries, Constriction, Pathologic, Stents, Cerebrovascular Disorders, United States Food and Drug Administration, Pharmaceutical Preparations, Bradycardia, Confidence Intervals, Carotid Stenosis
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