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Neurosurgery:
doi: 10.1227/01.neu.0000375271.39513.b2
Science Times

Carotid Endarterectomy Vs Endovascular Stenting: Recent Results From ICSS and CREST

KOMOTAR, RICARDO J.; STARKE, ROBERT M.; CONNOLLY, E. SANDER

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In both symptomatic and asymptomatic patients with significant extracranial carotid stenosis previous trials have demonstrated a significant benefit of carotid endarterectomy (CEA) over best medical treatment.1–5 A number of studies have investigated endovascular treatment (angioplasty with or without stenting) as an alternative to CEA.6–10 Originally, it was felt that endovascular treatment may be an alternative treatment in high risk patients. Although studies have demonstrated endovascular treatment results in fewer cranial nerve injuries and significant hematomas, 2 large randomized clinical trials comparing these treatments have failed to demonstrate decreased stroke or mortality rates in patient receiving endovascular treatment.7–10 In the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial symptomatic patients did not show non-inferiority of stenting compared with endarterectomy within 30 days after treatment.7,10 This trial was stopped early for reasons of futility and cost. The Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial was also stopped early, this time because of a significantly lower rate of periprocedural stroke or death in the endarterectomy group than in the stenting group.8,9

Recently, short-term results (120 days) of the International Carotid Stenting Study (ICSS), a randomized multicentrer, international, controlled trial with blinded adjudication of outcomes comparing stenting vs endarterectomy for recently symptomatic carotid artery stenosis demonstrated no significant difference in disabling stroke or death in patients receiving stenting (4.0%) as compared with CEA (3.2%; hazard ratio [HR] 1.28; 95% confidence interval [CI] 0.77–2.11).11 The incidence of stroke, death, or procedural myocardial infarction was significantly higher in the stenting group compared with the endarterectomy group (8.5% vs 5·2%; HR 1.69; 1.16–2.45, P = .006). Risks of any stroke (HR 1.92; 1.27–2.89) and all-cause death (HR 2.76; 1.16–6.56) were also higher in the stenting group than in the endarterectomy group. The rate of any stroke or death within 30 days of treatment in the stenting group was more than twice the rate recorded in the CEA group and there were also more fatal strokes and fatal myocardial infarctions in the stenting group. As expected, cranial nerve deficits and hematomas were significantly more common in the CEA group.

Meta-analysis of the EVA-3S, SPACE, and ICSS results demonstrate a 1.73 decreased risk of stroke, death, or myocardial infarction within 30 days in patients receiving carotid endarterectomy (95% CI 1.29–2.32).11 Although we are awaiting long-term results, one can only conclude from this preliminary data demonstrates that in the meantime, CEA should remain the treatment of choice for patients suitable for surgery.

Recently, results of the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), were presented at the International Stroke Conference.12 Subjects with symptomatic carotid stenosis (> 50% by angiography, > 70% by ultrasound (U/S), or >70% by computer tomography angiography [CTA]/magnetic resonance angiography [MRA]) or asymptomatic carotid stenosis (>60% by angiography, >70% by U/S, or >80% by CTA/MRA) were randomized to CEA or CAS (1:1) and were followed up to 4 years with neurological exams, best medical and risk factor management. The primary endpoint was a composite of any stroke, myocardial infarction, or death within 30 days, or ipsilateral stroke in follow up. Secondary endpoints contrast CAS and CEA by symptomatic status, sex, restenosis, health related quality of life and cost. There were 1326 symptomatic and 1196 asymptomatic subjects (35% female; 9.3% minorities) at 117 North American sites randomized to CAS or CEA (1:1).12 Primary analysis revealed no significant difference in the primary outcome between patients receiving stent-assisted carotid angioplasty and CES. It appears that results in patients are similar and certainly better than maximal medical therapy regardless of invasive intervention.11,12

Currently, we are awaiting final outcomes and subgroup analysis. Specific treatments may be more beneficial in patient subgroups according to age, sex, significant cardiac or pulmonary disease or history, history of radiation, presence of contralateral stenosis, severe tandem lesions, high cervical lesions, previous CEA, etc. Long-term outcomes will be necessary to assess the long term impact of recanalization rates in endovascular treated patients. In-depth functional outcomes may also be important in weighing the risks and benefits of treatments. Previous studies have shown significantly increased rates of non-disabling stroke in patients receiving endovascular therapy,11,13 and recent studies show that these strokes may have significant long-term impact on development of dementia.14 Furthermore, new stents coming to the market already raise the question as to whether results will already be outdated by the time of CREST publication.

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In conclusion, the new data from ICSS and CREST continue to support the practice that most patients with carotid stenosis are best treated with endarterectomy, but that stenting is a safe and efficacious alternative in those patients who are deemed poor candidates for surgery.

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RICARDO J. KOMOTAR

ROBERT M. STARKE

E. SANDER CONNOLLY

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REFERENCES

1. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273(18):1421–1428.

2. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351(9113):1379–1387.

3. Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998;339(20):1415–1425.

4. Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363(9420):1491–1502.

5. Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 2009;8(11):1006–1018.

6. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet. 2001;357(9270):1729–1737.

7. Eckstein HH, Ringleb P, Allenberg JR, et al. Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial. Lancet Neurol. 2008;7(10):893–902.

8. Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006;355(16):1660–1671.

9. 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;7(10):885–892.

10. Ringleb PA, Allenberg J, Bruckmann H, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006;368(9543):1239–1247.

11. International Carotid Stenting Study investigators, Dobson EJ, Featherstone RL, et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet. 2010;375(9719):985–997.

12. CREST: The Randomized Carotid Revascularization Endarterectomy vs Stenting Trial: Primary Results. Presented at International Stroke Conference, San Antonio, Texas, February 26, 2010.

13. Ederle J, Bonati LH, Dobson J, et al. Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol. 2009;8(10):898–907.

14. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003;361(9352):107–116.

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