The consensus statement  was proposed by the chairperson in the session, Professor Jesper Swedenborg, Stockholm and the session secretary dr Konstantinos Kostulas, Stockholm, together with the speakers in the session. The statement was then finally approved by the participants of the meeting, after listening to the different presentations.

The speakers in this session were Professor Martin Brown, London, Professor Michael Hennerici, Mannheim and Professor Jean-Louis Mas, Paris

Based on the results of the SPACE study and the EVA-3S study, is the recommendation to

- continue to evaluate angioplasty/stenting in RCT:s, but not recommend routine use?

- NOT recommend continued RCT:s, and not recommend routine use?

- recommend routine use, and if so

- which patients should be recommended for endarterectomy and which for angioplasty/stenting?

Surgery for symptomatic patients
(Update of statement from 2004).

Carotid endarterectomy (CEA) has been shown in two major trials, ECST (1-2) and NASCET (3-4), to reduce the risk of stroke in patients with carotid territory TIA or non-disabling ischaemic stroke in the previous 6 months having a severe stenosis of the ipsilateral carotid artery. The individual patient data from these two trials have been pooled with a third trial, VA 309 (5), using the NASCET method of measuring stenosis which is also used below.  There is now substantial evidence (grade A) that in symptomatic patients the benefit of CEA increases with the degree of stenosis, and is substantial for 70-99% stenosis of the symptomatic carotid artery: six patients were needed to treat to prevent one ipsilateral stroke (NNT=6; 95% CI 5-9) or any stroke or surgical death (NNT=6; 95% CI 5-10) (1-5). Patients with near occlusion (post-stenotic collapse or pseudo-occlusion) may not benefit from CEA (1-5). There is also grade A evidence that the benefit from CEA is lower in patients with 50-69% stenosis than for severe stenosis; twenty-four patients were needed to treat to prevent one ipsilateral ischaemic stroke (NNT=24; 95% CI 13-50), or fourteen to prevent one stroke of any origin, including surgical death (NNT=14; 95% CI 9-35) (1-3). For patients with 30-49% stenosis there is no benefit while surgery is actually harmful for patients with <30% stenosis (1-5). The studies show that the benefit from CEA is highly dependent on the duration of time since the presenting symptom. The absolute risk reduction from CEA is reduced by half if surgery is delayed beyond 2 weeks and further reduced by half if it is delayed beyond 4 weeks. Other variables in addition to the degree of stenosis and time may be useful in the selection of patients for surgery. This is particularly important for patients with 50-69% stenosis. The benefit is greater in men and patients aged 75 years or older (6-7).

Asymptomatic stenosis

Based on the pooled analysis there is grade A evidence that surgery is effective for asymptomatic stenosis (8-9), even though the absolute benefit is far less than for severe symptomatic stenosis  The large ACST-trial (8) has confirmed the findings of ACAS (9): In asymptomatic patients up to the age of 75, immediate CEA reduces the stroke risk within 5 years from 11.8% to 6.4% (net gain/absolute risk reduction 5.4%, 95% CI 3.0-7.8; p<0.0001; inclusive of 3% (NNT = 20 at five years for any stroke or surgical death; 95% CI=14-50). When the ten-year follow-up is completed we will be able to determine if surgery is worthwhile in the long term. Present data indicates that the benefit is questionable for women and patients aged above 75 years (6-7).

Who should perform CEA?

The present data suggests that surgery should be restricted to centres where the practice and complication rates are regularly monitored by surgeons and neurologists/ stroke physicians, and where complication rates of surgery are lower or at least comparable to those found in the clinical trials demonstrating efficacy. Monitoring should be prospective and independent of the surgeon involved and should be done with consideration of the applied indications for surgery and the resulting case mix at each centre.

Carotid angioplasty in Symptomatic Carotid Stenosis

There is no conclusive evidence from randomised trials including CAVATAS (10), EVA-3S (11) and SPACE (12), showing that carotid stenting is as safe as carotid endarterectomy in patients with symptomatic carotid stenosis, In addition there is very little data showing long term effectiveness of carotid stenting. At present, there is insufficient data supporting the use of carotid stenting in asymptomatic carotid stenosis.

Clinicians should be encouraged to enter patients into one of the on-going randomised trials. Until the final results of the on-going trials are available for a combined meta-analysis of safety and long-term effectiveness, stenting should not be routinely offered to patients suitable for carotid endarterectomy outside randomised trials.

Diagnosis of carotid stenosis

      Patients with carotid TIA or non disabling stroke require urgent specialist investigation. This should include medical history, neurological and cardiovascular examination, and imaging of the carotid arteries and the brain. Although trial evidence is based on catheter angiography, most centres now use duplex ultrasonography as a screening test in the diagnosis of carotid artery stenosis.
Ultrasound findings should to be supplemented with another non-invasive method (13).
   
Abbreviations:
ACAS, Asymptomatic carotid atherosclerosis study
ACST, Asymptomatic carotid surgery trial
CAS, Carotid artery stenting
CAVATAS, Carotid and Vertebral Artery Transluminal Angioplasty Study
CEA, carotid endarterectomy
CI, confidence interval
CT, computer tomography
ECST, European Carotid Surgery Trial
EVA-3S, Endarterectomy vs. Angioplasty in Patients with Symptomatic Severe Carotid Stenosis
ICA, internal carotid artery
MR, magnetic resonance
NASCET, North American Symptomatic Carotid Endarterectomy Trial
NNT, number needed to treat
PSV, Peak systolic velocity
SPACE, Stent-protected angioplasty versus carotid endarterectomy
TCD, transcranial Doppler
TIA, transient ischaemic attack
VA 309, the Veterans Administration (VA) Symptomatic Trial (Cooperative Studies Program 309 of the Department of Veterans Affairs)

References

1. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (0-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialist’s Collaborative Group. Lancet 1991; 337: 1235-1243.

2.European Surgery Trialist’s Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351: 1379-1387.

3. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325: 445-453.

4. North American Symptomatic Carotid Endarterectomy Trialist’s Collaborative Group. The final results of the NASCET trial. N Engl J Med 1998; 339: 1415-1425.

5. Mayberg MR, Wilson SE, Yatsu F, Weiss DG, Messina L, Hershey LA, Colling C, Eskridge J, Deykin D, Winn HR. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group, JAMA. 1991 Dec 18;266(23):3289-94.

6. Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ; Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004 Mar 20;363(9413):915-24.

7. Bond R, Rerkasem K, Cuffe R, Rothwell PM.  A systematic review of the associations between age and sex and the operative risks of carotid endarterectomy. Cerebrovasc Dis. 2005;20(2):69-77. Epub 2005 Jun 21. 

8. Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, Thomas D; MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004 May 8;363(9420):1491-502. Erratum in: Lancet. 2004 Jul 31;364(9432):416.  

9. No authors. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995 May 10;273(18):1421-8.

10. No authors. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet. 2001 Jun 2;357(9270):1729-37.

11. Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, Larrue V, Lièvre M, Leys D, Bonneville JF, Watelet J, Pruvo JP, Albucher JF, Viguier A, Piquet P, Garnier P, Viader F, Touzé E, Giroud M, Hosseini H, Pillet JC, Favrole P, Neau JP, Ducrocq X, for the EVA-3S Investigators. Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. N Eng J Med 2006; 355:1660-71..

12.SPACE Collaborative Group, Ringleb PA, Allenberg J, Bruckmann H, Eckstein HH, Fraedrich G, Hartmann M, Hennerici M, Jansen O, Klein G, Kunze A, Marx P, Niederkorn K, Schmiedt W, Solymosi L, Stingele R, Zeumer H, Hacke W.  30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006 Oct 7;368(9543):1239-47. Erratum in: Lancet. 2006 Oct 7;368(9543):1238. 

13. Wardlaw JM, Chappell FM, Stevenson M, De Nigris E, Thomas S, Gillard J, Berry E, Young G, Rothwell P, Roditi G, Gough M, Brennan A, Bamford J, Best J. Accurate, practical and cost-effective assessment of carotid stenosis in the UK. Health Technol Assess. 2006 Aug;10(30):iii-iv, ix-x, 1-182.