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Carotid StentingIntroductionCarotid Artery Atherosclerotic DiseaseCarotid artery stenosis is responsible for 20-30% of ischemic stroke.Cerebrovascular disease affects 750,000 people in US each yearStroke is 3rd leading cause of death in North America168,000 deaths in US/yearTreatment:Medical therapyAspirin, plavix, statinsRisk factor modificationCarotid Endarterectomy (CEA)Carotid artery stenting (CAS)

Carotid artery stenosis is responsible for 20-30% of ischemic stroke."1 The natural history of the disease is directly related to the severity of the lesion. Patients with hemodynamically significant carotid artery stenosis (>75% stenosis) have a 2% to 5% risk of suffering an ischemic stroke during the first year/2-45 Among patients with symptomatic (i.e., with previous stroke or transient ischemic attack), the risk of subsequent stroke is 12% to 13% during the first year and 30% to 37% within 5 years.(5'6) The pattern of progression of asymptomatic carotid artery stenosis to occlusion is unpredictable, and can be disastrous; at the time of occlusion, disabling stroke may occur in 20% of patients, and thereafter in 1.5% to 5% annually.(7) Nearly 80% of strokes due to artery-to- artery embolization in the carotid distribution may occur as the initial event without warning, emphasizing the need for prevention and treatment of carotid artery stenosis.70%2226 patients with stenosis < 70%Patients: 60% stenosis In centers with low peri-operative mortality and stroke rates (90% with >75% stenosisSignificantly more prior CEA or stent in the CAS arm

Peri-operative stroke or death:CEA: 2.4% CAS: 2.1%4 year follow up results:Any stroke:CEA 9.6%, CAS 8.6%Death/ non-fatal stroke:CEA 26.5%, CAS 21.8%Restenosis:Significantly higher in CAS armConclusion:Proof of principle that CAS with distal protection should be compared to CEA in a broad patient sample in a randomized trialJ Endovasc Ther 2003 & 20096Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk Patients (SAPPHIRE)Principle:The NASCET and ACAS trials exclude high risk patientsThese patients are being operated on in clinical practiceMulti-center randomized trial29 centers334 patients randomizedPatients:Patients were randomized if the team agreed that either CEA or CAS was appropriate At least one comorbidity that would deem them high risk for CEADuplex US:Symtomatic patients: >50%Asymptomatic patients: >80%

Procedures:All patients started on aspirinPlavix:CAS: plavix 24hrs pre-op & for 2-4wksCEA: No plavixCAS:Nitinol stent with distal cerebral protection deviceCEA:Not standardizedResults:Primary end point (death/ stroke/ MI at 30 days or death from neurologic cause w/in 1 yr)CAS 12% vs. CEA 20.1% (p=0.05)Conventional end-point (as above subtracting MI data)No differenceConclusion:CAS is not inferior to CEA for patients considered high risk for CEANEJM 20047Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Senting Study)Randomized controlled trial multicenter trial50 centers from Europe/ Australia/ Canada/ New Zealand1713 patients randomizedPatients:Included if >50% stenosis w/ symptoms attributable to the carotid diseaseExclusion:Massive strokePrevious CEA or stent on affected sidePlanned CABG or other surgery or contraindication to treatmentTreating physicians had to agree that either method would be suitableProcedures:CAS:Any trademarked device could be usedEmbolic protection device recommended but not mandatoryUse of aspirin/ plavix and heparinization recommendedCEA:Technique at the discretion of surgeonLancet 20108Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Senting Study)

Outcomes between initiation of treatment and 30 days

Outcomes between randomization of treatment and 120 days9

10Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Senting Study)Conclusions:Carotid endarterectomy is safer than carotid stenting in patients being treated for symptomatic carotid artery stenosis3.3% higher risk of stroke, death, or procedural MI within 120 daysThis is mainly due to a higher risk of non-disabling strokesRate of disabling stroke or death not significantly differentMore cranial nerve palsy and hematoma formation in CEA groupThe Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)Multi-center randomized trial comparing CEA to CAS in severe carotid stenosis117 sites in North America2522 patients randomized

Patients:Symptomatic with >50% by angio or >70% by US/ CTA/ MRIAsymptomatic with >60% by angio, >70% by US, or >80% by CTA/ MRIHigh risk patients remain eligible for the study; however, 4 year life expectancy requiredOctogenarians excluded in mid-trial due to stroke/ death rate

Outcomes released in press release form Composite endpoint (stroke, death, or MI w/in 30 days)CEA 6.8%, CAS 7.2%Any stroke w/in 30 days:CEA 2.3%, CAS 4.1%Major stroke < 1% for bothMICEA 2.3%, CAS 1.1%MI resulted in better quality of life than strokeIpsilateral stroke w/in 2 yrsEquivalentCEA 2.4%, CAS 2.0%J Stroke & Cerebrovasc Dis 2010, Stroke 201012ConclusionsCarotid endarterectomy has been established as the gold standard for treatment of carotid artery stenosisNASCET and ACAS trials

Carotid stenting remains to be proven as a viable alternative to endarterectomy in all patients

SAPPHIRE results suggest that CAS is at least equivalent to CEA in high risk patients

ICSS results suggest that CAS may cause higher peri-operative morbidity in symptomatic patients

CREST results suggest equivalency of CAS to CEA for all patients with carotid stenosis for composite endpoint of death / stroke/ MIHowever, stroke is more common in CAS, and has a greater impact on quality of life, that MI

13Future DirectionsNASCET and ACAS studies compared CEA to best medical treatmentAspirin utilized in bothPlavix and statins used at the discretion of the treating physicianStatins in only 14% of patients in NASCETStatins have subsequently been associated with decreased incidence of stroke29% relative reduction in stroke in one large meta-analysisJAMA 1997Risk ratio of 0.82 [95% CI 0.76 0.90] for fatal or non-fatal stroke in another large meta-analysisAm J Med 2004Future studies needed to re-assess CEA and CAS in light of optimal medical management

PathophysiologyCarotid disease is mostly due to atherosclerosis buildup of cholesterol and fibrotic tissue in the arterial wall results from both genetic and environmental influences Usually unifocal, 90% of lesions are located within 2 cm of the ICA origin. The degree of carotid stenosis stroke risk. Other uncommon causes: dissection, vasculitis, fibromuscular dysplasiasymptoms :progressive carotid stenosis leading to in-situ occlusion and hypoperfusion, intracranial arterial occlusion resulting from embolization (more common)

Natural History and Risk StratificationPatients with asymptomatic carotid bruits are more common than patients with symptomatic carotid stenosis. A carotid bruit is identified in 4% to 5% of patients age 45 to 80 years, (carotid stenosis 75%). Carotid stenoses 50% have been identified in 7% of men and 5% of women older than 65 years.Bruit may be absent if there is slow flow through a severe stenosis. The risk of progression of carotid stenosis is 9.3% per year; risk factors for progression include ipsilateral or contralateral ICA stenosis greater than 50%, ipsilateral ECA stenosis greater than 50%, systolic blood pressure greater than 160 mm Hg.

Stroke Risk In Symptomatic PatientsRisk of stroke in the first year11% for carotid stenosis 70% to 79%35% for carotid stenosis greater than or equal to 90%.Patients with carotid stenosis 70% to 99% had a 2-year ipsilateral stroke risk of 26%. Patients with near-occlusion have a lower stroke risk, ranging from 8% at 5 years to 11% at 1 year.Stroke Risk In Asymptomatic PatientsAnnual stroke risk is much lower than in symptomatic patients, less than 1 % for carotid stenoses less than 60% 1% to 2.4% for carotid stenoses greater than 60%.ACST (Asymptomatic Carotid Surgery Trial) no relationship between the risk of stroke and increasing stenosis severity from 60% to 99%.Patients referred for CABG high incidence of asymptomatic carotid stenosis (17% to 22% for stenosis > 50% and 6% to 12% for stenosis > 80%.) The risk of perioperative stroke after CABG 2% for carotid stenosis < 50%, 10% for carotid stenosis 50% - 80%, 19% for carotid stenosis > 80%.

Other factors that influence the risk of stroke include the clinical manifestations of TLA, prior silent stroke, contralateral disease, intracranial disease, intracranial collaterals, and plaque morphology. In the NASCET study, the 3-year risk of ipsilateral stroke was 10% after retinal TIAs and 20.3% after hemispheric TIAs.(33) The presence of concomitant intracranial disease raised the 3-year risk of stroke from 25% to 46% in patients with carotid stenosis 85% to 99%.(34) The prevalence of silent cerebral infarction in patients with asymptomatic carotid stenosis is estimated to be 15% to 20%