Revascularisation in carotid artey stenosis Journal Review

INTRODUCTION The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery and the carotid bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. Leads to ischemic stroke or transient ischemic attack (TIA) from embolization or thrombosis.

MANAGEMENT OF CAROTID STENOSIS CAROTID ENDARTERECTOMY CAROTID STENTING MEDICAL MANAGEMENT

ASYMPTOMATIC CAROTID DISEASE CAROTID ENDARTERECTOMY

Randomized controlled trials have established that carotid endarterectomy (CEA) is beneficial for patients with asymptomatic internal carotid artery stenosis of 60 to 99 percent The degree of benefit is not as good as for symptomatic carotid stenosis The evidence supporting CEA for asymptomatic carotid disease is less for women than for men

Asymptomatic Carotid Atherosclerosis Study (ACAS) Asymptomatic Carotid Surgery Trial (ACST)

10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST) Whether the addition of CE to aspirin plus risk factor modifications will affect the incidence of TIA or infarctions in patients with asymptomatic but haemodynamically significant carotid stenosis . This study randomly assigned patients during 1993-2003 to immediate CEA or deferral of any carotid artery procedure until a more definite indication was thought to have arisen, and followed them up until 2006-08 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

126 centers in 30 countries participated. Patients were eligible if: (1) they had severe unilateral or bilateral carotid artery stenosis (carotid artery diameter reduction at least 60%) (2) this stenosis had not caused stroke, transient cerebral ischaemia, or any other relevant neurological symptoms in the past 6 months

A total of 3120 patients entered the study between April 1993, and July 2003, with no significant differences in baseline characteristics between those randomly allocated immediate CEA and deferral.

560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure.

Medication was similar in both groups throughout the study Most were on antithrombotic and antihypertensive therapy. Net benefits were significant, both for those on lipid-lowering therapy and both for men and for women up to 75 years of age at entry.

Successful CEA for asymptomatic patients younger than 75 years of age reduces 10 year stroke risks. Half this reduction is in disabling or fatal strokes. For men and women younger than 75 years with asymptomatic stenosis,successful carotid surgery is beneficial.

Endarterectomy for Asymptomatic Carotid Artery Stenosis-ACAS Trial Objective To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis Prospective, randomized, multicenter trial. Thirty-nine clinical sites across the United States and Canada. December 1987 to December 1993 Total of 1662 patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter were randomized Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995

At baseline, recognized risk factors for stroke were similar between the two treatment groups. Intervention.  Daily aspirin administration and medical risk factor management for all patients; carotid endarterectomy for patients randomized to receive surgery. Main Outcome Measures Any transient ischemic attack, stroke, or death occurring in the perioperative period.

Results After a median follow-up of 2.7 years, the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 5.1% for surgical patients and 11.0% for patients treated medically (aggregate risk reduction of 53% [95% confidence interval, 22% to 72%]).

Conclusion Patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors

Degree of stenosis Data regarding degree of stenosis and stroke risk in asymptomatic carotid disease are conflicting Major asymptomatic CEA trials (ACAS and ACST) have not found a correlation between degree of stenosis and risk of stroke for patients with asymptomatic 60 to 99 percent stenosis.

Lewis RF, Abrahamowicz M, Côté R, Battista RN Lewis RF, Abrahamowicz M, Côté R, Battista RN. Predictive power of duplex ultrasonography in asymptomatic carotid disease. Ann Intern Med 1997; 127:13. The study analyzed the natural history of asymptomatic carotid disease in 714 patients who had serial carotid ultrasound examinations biannually for a mean follow-up of 3.2 years Progression to carotid stenosis of ≥80 percent was associated with a significantly higher risk for cerebrovascular events and death.

MEDICAL MANAGEMENT  Medical therapy that includes rigorous and compliant use of statins and antiplatelet agents, along with treatment of hypertension, cigarette smoking, and diabetes  Medical management may be a reasonable alternative to endarterectomy in patients with asymptomatic carotid disease.

A prospective population-based study identified 101 patients with an asymptomatic ≥50 percent carotid stenosis who were treated with intensive medical management. Over a mean follow-up of three years, there was only one minor ipsilateral stroke, for an average annual stroke rate of 0.34 percent (95% CI 0.1-1.87) By comparison, ipsilateral annual stroke rates in patients assigned to medical therapy in the major endarterectomy trials were approximately 2 to 3 percent Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke 2010; 41:e11.

Spence JD, Coates V, Li H, et al Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch Neurol 2010; 67:180. A prospective study from a single tertiary center compared treatment and outcome for two groups of patients with asymptomatic carotid stenosis of ≥60 percent: 199 patients who were enrolled from 2000 through 2002 and 269 patients who were enrolled from 2003 through 2007  At baseline, a reduction in the proportion of patients with intracranial microemboli detected by transcranial Doppler ultrasound (12.6 versus 3.7 percent)

In the first year of follow-up, a lower rate of carotid plaque progression (69 versus 23%) noted. In the first two years of follow-up, a decrease in the composite cardiovascular event endpoint of stroke, death, myocardial infarction, or CEA after development of symptoms (17.6 versus 5.6 percent)

Stenting trials Cochrane systematic review identified ten randomized controlled trials with 3178 patients that compared CEA with CAS in patients with symptomatic or asymptomatic carotid disease During long-term follow-up, the overall analysis found no significant difference between CEA and CAS in the risk of stroke or death

Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis-CREST Study Design CREST is a randomized, controlled trial 108 centers in the United States and 9 in Canada. Centers were required to have a team consisting of a neurologist, an interventionist, a surgeon, and a research coordinator Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11

Selection of Study Patients Considered to be symptomatic if they had had a transient ischemic attack amaurosis fugax, minor nondisabling stroke involving the study carotid artery within 180 days before randomization. Eligibility criteria were stenosis of 50% or more on angiography 70% or more on ultrasonography 70% or more on computed tomographic angiography or magnetic resonance angiography

Eligibility was extended in 2005 to include asymptomatic patients, for whom the criteria were stenosis of 60% or more on angiography, 70% or more on ultrasonography, or 80% or more on computed tomographic angiography or magnetic resonance angiography. Patients were excluded if they had had a previous stroke,chronic atrial fibrillation, myocardial infarction within the previous 30 days, or unstable angina.

At least 48 hours before carotid-artery stenting, patients received aspirin, at a dose of 325 mg twice daily, and clopidogrel at a dose of 75 mg twice daily. After the procedure, patients received 325-mg doses of aspirin daily for 30 days and either clopidogrel, 75 mg daily, or ticlopidine, 250 mg twice daily, for 4 weeks. At least 48 hours before carotid endarterectomy, patients received 325 mg of aspirin daily and continued to receive that dose for a year or more

The primary end point was the composite of any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization From December 2000 through July 2008, a total of 2522 patients were randomly assigned to one of the two treatments Dyslipidemia was more common among patients in the endarterectomy group than among those in the stenting group (85.8% vs. 82.9%, P=0.048), more than 80% of patients had severe stenosis

Primary End Point There was no significant difference in the estimated 4-year rates of the primary end point between carotid-artery stenting and carotid endarterectomy (7.2% and 6.8%, respectively; hazard ratio for stenting, 1.11; 95% confidence interval 0.81 to 1.51; P=0.51)  During the periprocedural period, the incidence of the primary end point was similar with carotid-artery stenting and carotid endarterectomy (5.2 and 4.5%, respectively; hazard ratio for stenting, 1.18; 95% CI, 0.82 to 1.68; P=0.38)

An interaction between age and treatment efficacy was detected (P=0 Crossover noted at an age of approximately 70 years. Carotid-artery stenting show greater efficacy at younger ages, and carotid endarterectomy at older ages. Cranial-nerve palsies were less frequent during the periprocedural period with carotid-artery stenting (0.3%, vs. 4.7% with carotid endarterectomy; hazard ratio, 0.07; 95% CI, 0.02 to 0.18).

CREST results indicate that carotid-artery stenting and carotid endarterectomy were associated with similar rates of the primary composite outcomes- periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke — among men and women with either symptomatic or asymptomatic carotid stenosis. The incidence of periprocedural stroke was lower in the endarterectomy group than in the stenting group The incidence of periprocedural myocardial infarction was lower in the stenting group.

SAPPHIRE The SAPPHIRE trial tested the hypothesis that CAS is not inferior to CEA in patients considered at high risk for carotid surgery who had either symptomatic or asymptomatic carotid stenosis Randomly assigned 334 patients to either CAS or CEA; both symptomatic patients with ≥50 percent carotid stenosis and asymptomatic patients with ≥80 percent carotid stenosis by angiography or ultrasound were enrolled.

More than 70 percent of patients had asymptomatic carotid disease. The stent used employed a distal embolic protection device Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004; 351:1493

The primary end point of SAPPHIRE was the cumulative incidence of a major cardiovascular event at one year, which included a composite of periprocedural death, stroke, or myocardial infarction (within 30 days after the procedure), and/or death or ipsilateral stroke between 31 days and one year. There was significant reduction in the primary composite end point for CAS compared with CEA (12.2 versus 20.1 percent, absolute difference 7.9 percent, 95% CI -0.7 to 16.4 percent)

There was no significant difference in the major secondary end point (ie, primary end point events plus death or ipsilateral stroke between one and three years) for CAS compared with CEA (24.6 versus 26.2 percent)  CONCLUSION CAS is not inferior to CEA in patients with asymptomatic disease 

Stenting in specific subgroups Elderly patients appear to do worse with CAS than with CEA In the prospective CREST trial, the rate of poor outcome in patients age 70 and older was higher with stenting than with endarterectomy.  In a meta-analysis of 41 studies of either CEA or CAS in patients ≥80 years old, the relative risks of death or myocardial infarction at 30 days were similar for patients having CAS and CEA, but the stroke rate was significantly higher for CAS (7.0 versus 1.9 percent) .

Pooled relative risk (RR) was more than three-fold higher for stroke after CAS (RR 2.18 versus 0.63 with CEA) Usman AA, Tang GL, Eskandari MK. Metaanalysis of procedural stroke and death among octogenarians: carotid stenting versus carotid endarterectomy. J Am Coll Surg 2009; 208:1124

PRACTICE GUIDELINES Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals American Heart Association/American Stroke Association. Stroke 2011; 42:517

Patients with asymptomatic carotid artery stenosis should be screened for other treatable risk factors for stroke with institution of appropriate lifestyle changes and medical therapy. Selection of asymptomatic patients for carotid revascularization should be guided by an assessment of comorbid conditions and life expectancy, and should include a thorough assessment of the risks and benefits of the procedure The use of aspirin in conjunction with CEA is recommended unless contraindicated.

Prophylactic CEA performed with <3 percent morbidity and mortality can be useful in highly selected patients with an asymptomatic carotid stenosis (minimum 60 percent by angiography, 70 percent by Doppler ultrasound).

Prophylactic CAS might be considered in highly selected patients with an asymptomatic carotid stenosis (≥60 percent on angiography, ≥70 percent on Doppler ultrasonography, or ≥80 percent on CT angiography or MR angiography). The usefulness of CAS as an alternative to CEA in asymptomatic patients at high risk for the surgical procedure is uncertain.

SYMPTOMATIC CAROTID STENOSIS

DEFINITION OF SYMPTOMATIC DISEASE “Focal neurologic symptoms that are sudden in onset and referable to the appropriate carotid artery distribution (ipsilateral to significant carotid atherosclerotic pathology), including one or more transient ischemic attacks characterized by focal neurologic dysfunction or transient monocular blindness, or one or more minor (nondisabling) ischemic strokes” 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

Vertigo and syncope are not caused by carotid stenosis The definition is includes only carotid symptoms within the previous six months

NASCET trial NASCET was initiated in the mid-1980s To investigate the efficacy of CEA compared with medical treatment in patients with symptomatic carotid atherosclerotic disease  Prospective, multi-center trial enrolled 659 patients who had had a hemispheric or retinal TIA or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic (ipsilateral) carotid artery. 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.

The study was prematurely terminated because of evidence that surgery was beneficial in this selected group of patients Patients followed up for a mean of 18 months Significant benefits for CEA A lower risk of any stroke or death (15.8 versus 32.3 percent) A lower risk of any ipsilateral stroke (9 versus 26 percent) A lower risk of major or fatal ipsilateral stroke (2.5 versus 13.1 percent) A lower risk of any major stroke or death (8.0 versus 19.1 percent)

CONCLUSION CEA was highly beneficial for patients with recent TIAs or nondisabling strokes with ipsilateral stenosis of 70 to 99 percent 

Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST) To assess the risks and benefits of carotid endarterectomy, primarily in terms of stroke prevention, in patients with recently symptomatic carotid stenosis. Multicentre, randomised controlled trial Enrolled 3024 patients. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet 1991

Enrolled men and women of any age, who within the previous 6 months had had at least one transient or mild symptomatic ischaemic vascular event in the distribution of one or both carotid arteries. Between 1981 -1994, allocated 1811 (60%) patients to surgery and 1213 (40%) to control Follow-up was until the end of 1995 (mean 6·1 years), and the main analyses were by intention to treat.

Findings The overall outcome (major stroke or death) occurred in 669 (37·0%) surgery-group patients and 442 (36·5%) control-group patients. The risk of major stroke or death complicating surgery (7·0%) did not vary with severity of stenosis. The risk of major ischaemic stroke ipsilateral to the unoperated symptomatic carotid artery increased with severity of stenosis, particularly above about 70—80% of the original luminal diameter .

The immediate risk of surgery was worth taking against the long-term risk of stroke without surgery when the stenosis was greater than about 80% diameter

Interpretation Carotid endarterectomy is indicated for most patients with a recent non-disabling carotid-territory ischaemic event when the symptomatic stenosis is greater than about 80%

Timing of surgery  After mild stroke or TIA — A pooled analysis of the NASCET and the ECST trials,found that CEA within two weeks of a nondisabling stroke or TIA significantly improved outcomes compared with later surgery In the subgroup of patients with 70 percent or greater carotid stenosis, CEA was associated with a 30.2 percent reduction in absolute risk of stroke in patients randomized within two weeks of their last event

Rothwell PM, Eliasziw M, Gutnikov SA, et al Rothwell PM, Eliasziw M, Gutnikov SA, et al. Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke. Stroke 2004; 35:2855 For patients with 50 to 69 percent stenosis, clinically important benefits from CEA were noted only in patients randomized within two weeks of their last event The decline in benefit of CEA over time was more rapid in women than in men. Surgical benefit in women was confined to those who had CEA within two weeks after their last event, irrespective of the degree of stenosis. CEA within two weeks of a nondisabling hemispheric stroke was not associated with an increased operative risk

After moderate to severe stroke The benefit of CEA for patients with moderate to severe ischemic stroke has not been evaluated in randomized clinical trials, as patients who have disabling stroke were not eligible for NASCET or ECST.

Emergency CEA for progressing/fluctuating stroke or crescendo TIA A 2009 systematic review identified 47 nonrandomized studies of CEA for recently symptomatic carotid stenosis that reported data on time from presenting event to CEA (including 18 studies that stratified emergent and nonemergent CEA. ) The rate of perioperative stroke or death was significantly higher with emergent CEA (14 versus 4 percent for nonemergency CEA) Rerkasem K, Rothwell PM. Systematic review of the operative risks of carotid endarterectomy for recently symptomatic stenosis in relation to the timing of surgery. Stroke 2009; 40:e564.

Gender Benefit of CEA may be greater for men than for women The risk of stroke ipsilateral to a symptomatic carotid stenosis is significantly lower for medically treated women than men, while the perioperative risk of death from CEA is significantly higher in women than in men. CEA is beneficial for women with 70 to 99 percent symptomatic carotid stenosis, and the five-year absolute risk reduction in stroke is similar for men and women

CEA is not beneficial for most women with 50 to 69 percent symptomatic carotid stenosis Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363:915. Alamowitch S, Eliasziw M, Barnett HJ, et al. The risk and benefit of endarterectomy in women with symptomatic internal carotid artery disease. Stroke 2005; 36:27

Contralateral carotid stenosis or occlusion CEA is likely to be beneficial for patients who have symptomatic ipsilateral carotid stenosis and coexisting severe contralateral carotid stenosis or occlusion. They are at higher perioperative risk than those without a severe contralateral carotid artery stenosis.

Gasecki AP, Eliasziw M, Ferguson GG, et al Gasecki AP, Eliasziw M, Ferguson GG, et al. Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. J Neurosurg 1995; 83:778 Medically treated patients with an occluded contralateral carotid were twice likely to have an ipsilateral stroke compared with those with severe or mild to moderate disease (hazard ratio 2.36 and 2.65). Among surgically treated patients, the perioperative risk of stroke and death was higher in those with a totally occluded or mild to moderately stenotic contralateral vessel (4 and 5 percent, respectively) compared with those without contralateral disease. Patients who had CEA had a significantly better outcome than patients treated medically.

CAROTID STENTING

ICSS trial (CAVATAS 2) 1713 adults (age >40 years) with symptomatic carotid artery stenosis were randomly assigned to treatment with either CEA or CAS  All patients had carotid stenosis that was >50 percent by noninvasive imaging such as duplex ultrasound. International Carotid Stenting Study investigators, Ederle J, Dobson J, 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; 375:985

Interim analysis at 120 days The proportion of patients who reached the combined endpoint of stroke, death, or myocardial infarction was significantly higher for the stenting group than the endarterectomy group (8.5 versus 5.2 percent, hazard ratio 1.69, 95% CI 1.16-2.43) The stenting group also had significantly higher rates for the endpoints of any stroke (7.7 versus 4.1 percent), any stroke or death (8.5 versus 4.7 percent), and all cause death (2.3 versus 0.8 percent) There was no significant difference between the stenting and endarterectomy groups for the endpoint of disabling stroke (4.0 versus 3.2 percent)

A subanalysis of 231 patients in the ICSS -brain MRI found that the proportion of patients with new ischemic brain lesions on diffusion-weighted MRI at a median of one day after treatment was significantly higher in the stenting group than in the endarterectomy group (50 versus 17 percent, odds ratio 5.2, 95% CI 2.8-9.8)  International Carotid Stenting Study investigators, Ederle J, Dobson J, 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; 375:985. Bonati LH, Jongen LM, Haller S, et al. New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS). Lancet Neurol 2010; 9

SPACE The SPACE trial was a multicenter European study designed to test the hypothesis that CAS is not inferior to CEA for the treatment of severe symptomatic carotid stenosis  Assigned 1183 patients to either CAS or CEA Excluded high-risk patients with uncontrolled hypertension or severe concomitant disease and recurrent carotid stenosis after surgery or stenting. SPACE Collaborative Group, Ringleb PA, Allenberg J, 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; 368:1239.

At 30 days - no significant difference between CAS and CEA in the primary composite outcome measure, death or ipsilateral ischemic stroke (6.8 versus 6.3 percent No statistically significant difference between CAS and CEA in the composite endpoint of any periprocedural stroke or death and ipsilateral ischemic stroke up to two years after the procedure Recurrent carotid stenosis ≥70 percent was significantly more frequent in the CAS group

Use of embolic protection devices with stenting was optional Used in only 27 percent of patients treated with CAS . No significant difference in the primary outcome of death or ipsilateral ischemic stroke at 30 days between patients treated with and without embolic protection (7.3 and 6.7 percent, respectively, 90% CI 0.53-2.25).

EVA-3S  Hypothesis - CAS is not inferior to CEA for the treatment of severe symptomatic carotid stenosis  Randomly assigned 527 patients with this condition to CAS or CEA. The study excluded high-risk patients with unstable angina, uncontrolled diabetes, or uncontrolled hypertension, and patients with previous carotid revascularization ( recurrent carotid stenosis). Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006

The incidence of any stroke or death at 30 days, the composite primary outcome measure, was significantly higher with stenting than with CEA (9.6 versus 3.9 percent, relative risk 2.5, 95% CI 1.2-5.1). The trial was stopped prematurely due to an excess number of deaths in the CAS group. The prespecified main secondary outcome (any periprocedural stroke or death and any non-periprocedural ipsilateral stroke occurring in up to four years of follow-up) was also significantly higher with stenting than with CEA (11.1 versus 6.2 percent, hazard ratio 1.97, 95% CI 1.06-3.67) .

The risk of ipsilateral stroke after the periprocedural period was low, and similar in both treatment groups. The main criticism of EVA-3S -heterogeneity of operator experience, stent types (Interventional clinicians were required to have performed only two stenting procedures with any new device before its use in EVA-3S,five different stents and seven different protection devices were used in the trial )

CREST  A secondary analysis showed that for the subgroup of patients with symptomatic carotid disease, the periprocedural rate of stroke and death was significantly higher for those assigned to stenting compared with endarterectomy (6.0 versus 3.2 percent, HR 1.89, 95% CI 1.1-3.2)

Effect of age 2010 meta-analysis of the three largest trials of patients with symptomatic carotid disease (ICSS, EVA-3S, and SPACE)-estimated risk of stroke or death for patients age 70 and older was approximately two-fold higher for the carotid stenting group compared with the endarterectomy group (103 of 856 versus 51 of 865 [12.0 versus 5.9 percent], risk ratio 2.04, 95% CI 1.48—2.82) . The estimated risk of stroke or death for patients age 69 and younger was similar for the carotid stenting and endarterectomy groups (50 of 869 versus 48 of 843 [5.8 versus 5.7 percent], risk ratio 1.00, 95% CI 0.68—1.47). Carotid Stenting Trialists' Collaboration, Bonati LH, Dobson J, et al. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data. Lancet 2010; 376:1062.

CREST trial- the rate of adverse events in patients age 70 and older was significantly higher with stenting than with endarterectomy

MEDICAL MANAGEMENT These therapies include aggressive treatment with statins, antiplatelet agents, and antihypertensive agents Statin treatment can also reduce the incidence of first and recurrent stroke. Guidelines issued in 2011 by the AHA/ASA recommend optimal medical therapy for all patients with carotid artery stenosis and a TIA or stroke, including antiplatelet therapy, statin therapy, and risk factor modification 

Embolic protection devices Subdivided into distal and proximal types. Distal EPDs are more commonly used

Embolic protection device

Distal devices Devices that occlude or filter distal blood flow are designed to catch debris dislodged during stent placement. Deploy distal filters or balloons Disadvantages They must pass across the stenosis-may dislodge emboli. Tight lesions may require predilatation before the distal device can be placed. The presence of the EPD in the distal carotid artery may induce vasospasm that can severely narrow the outflow and cause stroke if prolonged. Distal EPDs may cause complications related to vessel wall injury or to difficulty with removal of the distal device itself

Proximal devices Deploy occlusion balloons in the external carotid artery and the common carotid artery Following stent insertion, the proximal internal carotid artery is suctioned to remove debris prior to deflating the occlusion balloon Disadvantages They are larger than distal devices. Cerebral ischemia may occur Injury to the common and external carotid arteries may occur with balloon inflation

Benefit from EPDs has not been established in randomized controlled trials Data from existing randomized controlled trials suggest that EPDs are not effective for preventing symptomatic stroke or new ischemic brain lesions on MRI (butconclusion is based upon subgroup analyses with relatively small numbers of patients and events) 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.

A prespecified subgroup analysis of patients assigned to CAS in the SPACE trial showed no significant difference in the 30-day outcome of ipsilateral stroke or death between those who were treated with (n = 151) or without (n = 416) embolic protection (7.3 and 6.7 percent, respectively)  SPACE Collaborative Group, Ringleb PA, Allenberg J, 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; 368:1239.

A 2007 meta-analysis, with data available from two randomized trials, found no significant difference for the combined endpoint of death or any stroke comparing treatment with or without cerebral protection (odds ratio 0.77, 95% CI 0.41-1.46) Ederle J, Featherstone RL, Brown MM. Percutaneous transluminal angioplasty and stenting for carotid artery stenosis. Cochrane Database Syst Rev 2007

A systematic literature review of observational studies published in 2008 reported 700 patients who had CAS with MRI data available . The rate of new ipsilateral DWI lesions on diffusion weighted MRI was lower for CAS procedures using an EPD compared with those done without an EPD (33 versus 45 percent) Schnaudigel S, Gröschel K, Pilgram SM, Kastrup A. New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature. Stroke 2008; 39:1911.

Many prospective stent registries and case series show that the periprocedural risk of stroke after CAS is significantly lowered with the use of an EPD. Brown MM. Carotid artery stenting--evolution of a technique to rival carotid endarterectomy. Am J Med 2004; 116:273. Theron JG, Payelle GG, Coskun O, et al. Carotid artery stenosis: treatment with protected balloon angioplasty and stent placement. Radiology 1996; 201:627.

PRACTICE GUIDELINES Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals American Heart Association/American Stroke Association. Stroke 2011; 42:517

For patients with recent TIA or ischemic stroke within the past six months and ipsilateral severe (70 to 99 percent) carotid artery stenosis, CEA is recommended if the perioperative morbidity and mortality risk is estimated to be <6 percent. For patients with recent TIA or ischemic stroke and ipsilateral moderate (50 to 69 percent) carotid stenosis, CEA is recommended depending on patient-specific factors, such as age, sex, and comorbidities, if the perioperative morbidity and mortality risk is estimated to be <6 percent.

When the degree of stenosis is <50 percent, there is no indication for carotid revascularization by either CEA or CAS. When CEA is indicated for patients with TIA or stroke, surgery within two weeks is reasonable rather than delaying surgery

CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the lumen of the internal carotid artery is reduced by >70 percent by noninvasive imaging or >50 percent by catheter angiography.

CAS may be considered among patients with symptomatic severe stenosis (>70 percent) in whom stenosis is difficult to access surgically medical conditions are present that greatly increase the risk for surgery radiation-induced stenosis restenosis after CEA.

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