EVA3S: Endarterectomy Versus Angioplasty in Patients With Severe Symptomatic Carotid Stenosis

• - Any stroke or death within 30 days of the procedure
• - Any stroke or death within 30 days of the procedure plus ipsilateral stroke during the follow-up period (2 to 4 years).

• Clinical: Myocardial infarction within 30 days of the procedure [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Clinical: Myocardial infarction within 30 days of the procedure
• Other complications within 30 days of the procedure: cerebral (transient ischemic attack [TIA]) [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Other complications within 30 days of the procedure: cerebral (transient ischemic attack [TIA])
• locoregional (e.g. cranial nerve palsy, complications at the site of puncture) [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  locoregional (e.g. cranial nerve palsy, complications at the site of puncture)
• General: Any disabling stroke or death within 30 days of the procedure plus disabling or fatal ipsilateral stroke during the follow-up period [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  General: Any disabling stroke or death within 30 days of the procedure plus disabling or fatal ipsilateral stroke during the follow-up period
• Any stroke or death within 30 days of the procedure plus any stroke (or any stroke or death) during the follow-up period [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Any stroke or death within 30 days of the procedure plus any stroke (or any stroke or death) during the follow-up period
• TIA during the follow-up period [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  TIA during the follow-up period
• Functional status at the end of the study [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Functional status at the end of the study
• Anatomical: Carotid restenosis (> 70% on carotid ultrasound) [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Anatomical: Carotid restenosis (> 70% on carotid ultrasound)
• Integrity of the stent 2 years after the procedure (on cervical radiogram) [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Integrity of the stent 2 years after the procedure (on cervical radiogram)

• Clinical
• · Myocardial infarction within 30 days of the procedure.
• · Other complications within 30 days of the procedure: cerebral (TIA); locoregional (e.g. cranial nerve palsy, complications at the site of punction); general.
• · Any disabling stroke or death within 30 days of the procedure plus disabling or fatal ipsilateral stroke during the follow-up period. Any stroke or death within 30 days of the procedure plus any stroke (or any stroke or death) during the follow-up peri
• · TIA during the follow-up period.
• · Functional status at the end of the study.q Anatomical
• · Carotid restenosis (> 70% on carotid ultrasound).
• · Integrity of the stent 2 years after the procedure (on cervical radiogram).

The purpose of this study is to evaluate whether carotid angioplasty with stent (CAS) is as safe and effective as carotid surgery in regards to:

1. the risk of stroke and death within 30 days of the procedure;
2. the long-term risk of ipsilateral carotid territory stroke, in patients with recently symptomatic, severe carotid stenosis suitable for both CAS and carotid endarterectomy.

Findings from two large randomized clinical trials - NASCET and ECST - have established endarterectomy as the standard treatment for severe symptomatic carotid artery stenosis. Compared to endarterectomy, stenting with or without cerebral protection has the advantage of avoiding general anesthesia and incision in the neck that could lead to nerve injury and wound complications. The costs may be less than those of surgery, mainly because of a shorter hospital stay. However, stenting also carries a risk of stroke and local complications. Unlike endarterectomy, which has known long-term benefits, stenting does not remove the atheromatous plaque, and the long-term efficacy of this technique needs also to be assessed. Several trials are in progress in Europe and the United States.

We established this trial to evaluate whether stenting is not inferior to endarterectomy concerning (a) the risk of stroke or death within 30 days of procedure and (b) the long-term risk of ipsilateral stroke, in patients with recently symptomatic, severe carotid stenosis.

• Transient Ischemic Attack
• Carotid Stenosis
• Atherosclerosis

• Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, Larrue V, Lievre M, Leys D, Bonneville JF, Watelet J, Pruvo JP, Albucher JF, Viguier A, Piquet P, Garnier P, Viader F, Touze E, Giroud M, Hosseini H, Pillet JC, Favrole P, Neau JP, Ducrocq X; EVA-3S Investigators. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006 Oct 19;355(16):1660-71.
• Rantner B, Goebel G, Bonati LH, Ringleb PA, Mas JL, Fraedrich G; Carotid Stenting Trialists' Collaboration. The risk of carotid artery stenting compared with carotid endarterectomy is greatest in patients treated within 7 days of symptoms. J Vasc Surg. 2013 Mar;57(3):619-626.e2; discussion 625-6. doi: 10.1016/j.jvs.2012.08.107. Epub 2012 Dec 11.
• Mas JL, Trinquart L, Leys D, Albucher JF, Rousseau H, Viguier A, Bossavy JP, Denis B, Piquet P, Garnier P, Viader F, Touzé E, Julia P, Giroud M, Krause D, Hosseini H, Becquemin JP, Hinzelin G, Houdart E, Hénon H, Neau JP, Bracard S, Onnient Y, Padovani R, Chatellier G; EVA-3S investigators. 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 Oct;7(10):885-92. Epub 2008 Sep 5.

Inclusion Criteria:

• In brief, patients are eligible if they have experienced a carotid TIA or non disabling stroke within 4 months before randomisation and if they have an atherosclerotic stenosis of the region of the ipsilateral carotid bifurcation of 60% or more, as determined by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method, that investigators believe is suitable for both carotid endarterectomy and endovascular treatment. The degree of stenosis warranting treatment initially set at 70% or more was subsequently set at 60% or greater to reflect current generally accepted practice in the treatment of symptomatic carotid stenosis. The presence of a 60% or more ipsilateral carotid stenosis has to be confirmed by conventional digital subtraction angiography or the combination of carotid Duplex scanning and magnetic resonance angiography, provided the results of these non-invasive techniques are concordant.

Exclusion Criteria:

• Patients cannot be included if they have a disabling stroke (mRS >=3), a non atherosclerotic carotid disease, a severe intracranial carotid artery stenosis, contra-indications to heparin, ticlopidine or clopidogrel.
• There is no age limit.
• The presence of contralateral occlusion and/or the angiographic appearance of the stenotic lesion are not factors in treatment selection. The randomisation algorithm takes centre and degree of stenosis (more or less than 90% stenosis) into account. Patients must be treated as soon as possible after random assignment, in any case within 2 weeks of randomisation.