doi:10.1016/j.jacc.2007.10.052 2008;51;979-985 J. Am. Coll. Cardiol.

and L. Nelson Hopkins Elad I. Levy, J. Mocco, Rodney M. Samuelson, Robert D. Ecker, Babak S. Jahromi,

Optimal Treatment of Carotid Artery Disease

This information is current as of March 16, 2008

http://content.onlinejacc.org/cgi/content/full/51/10/979located on the World Wide Web at:

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STATE-OF-THE-ART PAPER

Optimal Treatment of Carotid Artery Disease

Elad I. Levy, MD,*†‡ J Mocco, MD, MS,*‡ Rodney M. Samuelson, MD,*‡ Robert D. Ecker, MD,*‡Babak S. Jahromi, MD, PHD,*‡ L. Nelson Hopkins, MD*†‡

Buffalo, New York

Extracranial carotid artery disease accounts for approximately 25% of ischemic strokes. Although carotid endar-terectomy (CEA) is the established gold standard for carotid revascularization, carotid artery angioplasty andstenting (CAS) is continually developing into a safer and more efficacious method of stroke prevention. Embolicprotection, improving stent designs, and ever-increasing surgeon experience are propelling CAS towards equi-poise with and possible superiority to CEA. One multicenter randomized trial and several nonrandomized regis-tries have successfully established CAS as an accepted treatment for high-risk patients. Clinicians must strive toperform well-designed clinical trials that will continue to aid understanding and improve application of both en-dovascular and open techniques for extracranial carotid revascularization. We review the data published to dateregarding the indications for and recent developments in the use of CAS. (J Am Coll Cardiol 2008;51:979–85)© 2008 by the American College of Cardiology Foundation

ublished by Elsevier Inc. doi:10.1016/j.jacc.2007.10.052

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arotid artery angioplasty and stenting (CAS) has steadilyeveloped over the preceding decade. Current data regard-

ng CAS and carotid endarterectomy (CEA) suggest thatAS is quickly gaining ground on CEA as a first-line

reatment of extracranial carotid stenosis. Clinicians mustontinue to refine their understanding of the appropriatendications for both CAS and CEA. This is done throughigorous, well-designed research. We review the data sup-orting the implementation of CAS for extracranial athero-cclusive carotid artery disease.

ackground

ndications for and outcomes of CEA have been extensivelytudied. The support for CEA utilization is generated from 4ell-designed multicenter, randomized clinical trials—ASCET (North American Symptomatic Carotid Endarter-

ctomy Trial) (1,2), ECST (European Carotid Surgery Trial)3,4), ACAS (Asymptomatic Carotid Atherosclerosis Study)5), and ACST (Asymptomatic Carotid Surgery Trial) (6).he NASCET (1,2) and ECST (4) trials addressed the use of

rom the *Departments of Neurosurgery and Toshiba Stroke Research Center andDepartment of Radiology, School of Medicine and Biomedical Sciences, Universityt Buffalo, State University of New York, Buffalo, New York; and the ‡Departmentf Neurosurgery, Millard Fillmore Gates Hospital, Kaleida Health, Buffalo, Nework. Dr. Hopkins receives grant support from Boston Scientific, Cordis, and Micrusndovascular and honoraria from Bard, Boston Scientific, Cordis, and Medsn; owns

tock in APW Holding, Inc., Boston Scientific, and Micrus Endovascular; is aonsultant for Abbott, Bard, Boston Scientific, and Cordis; and is a board member,rustee, or officer with Access Closure, market Rx, and Micrus Endovascular. Dr.evy receives grant support and honoraria from Boston Scientific and Cordis, patent

oyalties from Zimmer Spine, and financial support from Abbott Vascular and ev3 forarotid stent training. Dr. Mocco is supported by a research grant from the Brain

pneurysm Foundation.Manuscript received October 26, 2007; accepted October 31, 2007.

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EA for symptomatic patients with 70% to 99% carotidtenosis or selected patients with 50% to 69% stenosis. Thesetudies resulted in class IA indications for the use of CEA inymptomatic patients meeting appropriate criteria (7). How-ver, it is important to realize that the general population ofatients with carotid stenosis has substantially different demo-raphics than those patients who met the strict eligibilityriteria for these studies (8). For instance, NASCET excludedatients �80 years old and those with intracranial carotidtenosis more severe than the surgically accessible lesion; liver,idney, or lung failure; cardiac valve or rhythm disorder;revious ipsilateral CEA; uncontrolled hypertension or diabe-es; recent myocardial infarction (MI); or major surgery (1).uch patients were considered to have excessive perioperativeorbidity (i.e., high risk). Since NASCET was published,

atients considered for carotid revascularization are oftenivided into low- and high-risk groups, and, in fact, recentAS trial investigators have used such surgical risk stratifica-

ion as an integral part of their study design.The ACAS (5) and the ACST (6) trials addressed the use

f CEA for asymptomatic patients. The degree of benefitrom CEA for asymptomatic lesions is substantially less,nd the indications for revascularization are still debated.he ACAS and ACST trials demonstrated a 5.4% to 5.9%

bsolute risk reduction over 5 years (5,6). Therefore,eriprocedural risks are particularly relevant to the decisionnalysis for treatment of asymptomatic patients, with aorbidity of �3% minimizing any benefit. Despite this,ith the publication of ACAS, nearly 75% of CEAs in the.S. are performed on asymptomatic patients (9).In the aforementioned trials, carefully selected low-risk

atients were treated by highly experienced surgeons atby Michael Jaff on March 16, 2008

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high-volume medical centers.The low complication rates seenin NASCET and ACAS are of-ten not obtained in the generalpopulation. Studies have demon-strated perioperative stroke anddeath to range from 0% (10) to11.1% (11) for symptomatic pa-tients and 0% (12) to 5.5% (11)for asymptomatic patients. Infact, a study of Medicare mortal-ity data from hospitals participat-ing in NASCET and ACASdemonstrated a 1.4% periopera-tive mortality (8) compared with

.6% reported in NASCET (1) and 0.1% reported in ACAS5). Perhaps equally concerning, CEA-related mortalityates have been demonstrated to be higher (2.5%) forow-volume hospitals (8), although other studies have ar-ued that only small differences exist between mortalityates at high- and low-volume hospitals (13).

Treatment decisions are also dependent on patient-pecific factors. The presence of comorbidities has signifi-ant impact on outcome after CEA. Perioperative strokend death rates for common comorbidities include conges-ive heart failure, 8.6% (14,15); age over 75 years, 7.5%14,15); post-endarterectomy restenosis, 10.8% (16); ipsi-ateral carotid siphon stenosis, 13.9% (14); intraluminalhrombus, 10.7% to 17.9% (14,17); contralateral carotidcclusion, 14.3% (18); and CEA combined with coronaryrtery bypass grafting, 16.4% to 26.2% (19,20). It is impor-ant to note that in the presence of such comorbidities theatural history of carotid disease itself is more grim. The

nvestigators of the ACSRS “natural history” study followedp 1,115 patients with asymptomatic internal carotid arterytenosis treated with medical therapy alone (21) and iden-ified significant differences in patient subgroups with re-pect to stroke and death risk. The highest risk group (82%o 99% stenosis by NASCET criteria [1], history of con-ralateral transient ischemic attack [TIA], and serum cre-tinine level �0.085 mmol/l) had a 4.3% annual ipsilat-ral stroke rate compared with 0.7% in the lowest riskroup (21,22).It should also be noted that since the aforementionedajor randomized CEA trials were begun, best medical

herapy has improved. In NASCET, the primary medicalntervention was 1,300 mg of aspirin per day (1). This dosef aspirin is no longer used because lower doses are provenqually efficacious with fewer side effects (23–25). Otherntiplatelet drugs, such as clopidogrel and ticlopidine, arelso now available (26,27); and the aspirin-dipyridamoleombination was shown to be more efficacious than aspirinlone (28). Methods for blood pressure control were notpecified in NASCET, whereas it is now known that bloodressures below 120 to 130/70 mm Hg are optimum for

Abbreviationsand Acronyms

ACE � angiotensin-converting enzyme

CAS � carotid arterystenting

CEA � carotidendarterectomy

DWI � diffusion-weightedimaging

MI � myocardial infarction

TIA � transient ischemicattack

ardiovascular risk reduction in patients with medical co- r content.onlinejacc.orgDownloaded from

orbidities (7,29,30) and that for primary stroke prevention10-mm Hg reduction in systolic blood pressure produces31% relative risk reduction for stroke (31). For secondary

troke prevention, angiotensin-converting enzyme (ACE)nhibitors (29,32) and the combination of a thiazide diureticith an ACE inhibitor (32) have now been proven effective.dditionally, in the past decade, statins have assumed arominent role in cerebrovascular and cardiovascular riskodification (33–37). In a study of patients receiving medical

reatment for severe carotid artery disease, statin use wasssociated with significantly lower rates of stroke, MI, or death38). It is likely that medical therapy improvement for carotidtherosclerotic disease and related comorbidities shouldrompt periodic re-evaluation and risk-benefit analysis fine-uning for medical therapy versus surgical intervention.

With the great deal of complexity regarding risk assess-ent in this complex patient population, current standards

re limited to minimizing overall surgical risk in order toaximize the likely benefit from surgery. Currently, the

uidelines of the American Heart Association (7) and theanadian Neurosurgical Society (39) establish an upper

imit of 6% for perioperative risk in symptomatic patients7) and a 3% upper limit in asymptomatic patients, assum-ng a life expectancy of �5 years (20).

ublished Data Regarding CAS

he first randomized trial comparing endovascular and surgicalreatments for carotid stenosis patients, CAVATAS (CArotidnd Vertebral Artery Transluminal Angioplasty Study) (40),hich was published in 2001, included 504 patients enrolledetween 1992 and 1997 and was designed to comparealloon angioplasty alone versus CEA. Stents, when theyecame available, were incorporated as well but only ac-ounted for 26% of cases. Twenty-four centers in Europe,ustralia, and Canada participated, and like previous CEA

rials, high-risk surgical patients were excluded from enroll-ent—including those with recent MI, poorly controlled

ypertension or diabetes mellitus, renal disease, respiratoryailure, inaccessible carotid stenosis, or severe cervical spon-ylosis. The CAVATAS trial demonstrated no statisticallyignificant difference between endovascular and surgicalreatment in the rate of disabling stroke or death within 30ays (6.4% CAS vs. 5.9% CEA) and no significant differ-nce in the 3-year ipsilateral stroke rate. These earlyncouraging results generated a great deal of interest inAS, and further studies were undertaken.The Wallstent trial (41,42), the first multicenter random-

zed trial designed from inception to evaluate CEA andAS equivalence, enrolled a total of 219 symptomaticatients with 60% to 99% stenosis. Thirty-day stroke oreath rates were 12.1% with CAS and 4.5% with CEA (p �.049). Additionally, 12.1% of CAS patients suffered ipsi-ateral stroke, procedure-related death, or vascular death at

year versus 3.6% of CEA patients (p � 0.022), and, as a

esult, the trial was halted by the Data Safety and Moni-by Michael Jaff on March 16, 2008

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981JACC Vol. 51, No. 10, 2008 Levy et al.March 11, 2008:979–85 Optimal Treatment of Carotid Artery Disease

oring Committee after an interim analysis demonstratedorse outcomes for the CAS group. Critical to interpreting

hese results is the fact that the Wallstent trial did notmploy the use of distal protection devices. A significantortion of major CAS neurological complications are due totheromatous material embolization (43–46). Devices thatapture embolic debris released during CAS have signifi-antly improved procedural safety (43,46–50).

One of the first trials to utilize embolic protection wasaRESS (Carotid Revascularization Using Endarterectomyr Stenting Systems) (51,52), a multicenter, nonrandom-zed, prospective study comparing CAS with embolic pro-ection (n � 143) and CEA (n � 254) in symptomatic32%) and asymptomatic (68%) patients with low- andigh-surgical risk. An important feature of CaRESS washat the treatment procedure was chosen by the treatinghysician and the patient, not randomized. Although thistudy design likely introduced selection bias, the CaRESSrial represents a generalized perspective on carotid revas-ularization and more closely represents its ‘real world’pplication. Baseline group demographics were similar,xcept patients with previous carotid intervention moreften received CAS. No statistically significant differenceetween 30-day and 1-year death or stroke rates existedetween CAS and CEA (2.1% vs. 3.6% and 10.0% vs.3.6%, respectively), nor did significant differences exist forestenosis, residual stenosis, repeat angiography, and needor carotid revascularization. Overall morbidity and mortal-ty approached NASCET (1,2) and ACAS (5) standardsnd represented the lowest rates among the major CASrials to date. The low stroke and death rates may bettributable to the ability of the treating physician toonsider patient-specific factors and successfully assign eachatient to the safest therapy.Carotid artery stenting was well established as a treat-ent option for high-risk patients by SAPPHIRE (Stent-

ng and Angioplasty with Protection in Patients at Highisk for Endarterectomy) (53), a randomized, multicenter

rial to determine CAS noninferiority to CEA in high-riskatients. Eligible patients (n � 344) had symptomatictenosis of at least 50% or asymptomatic stenosis of at least0%. The 30-day MI, stroke, or death rate was 4.8% forAS and 9.8% for CEA (p � 0.09). Much of this differenceas secondary to MIs in the CEA group, and although not

eported in SAPPHIRE, the 30-day rate of stroke andeath was �4.8% for CAS patients and �5.6% for CEAatients. At 1 year, 12.2% of CAS patients had sufferedtroke, MI, or death versus 20.1% of CEA patients (non-nferiority analysis: p � 0.004; superiority analysis:ntention-to-treat p � 0.053, as-treated p � 0.048). Myo-ardial infarction and major ipsilateral stroke rates wereignificantly better after CAS versus CEA (2.5% vs. 8.1%,� 0.03; 0% vs. 3.5%, p � 0.02; respectively).As SAPPHIRE had shown such clear noninferiority in

igh-risk patients, the SPACE (Stent-supported Percuta-

eous Angioplasty of the Carotid artery versus Endarterec- r

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omy) trial (54) set out to establish noninferiority for CASompared with CEA in patients with low risk. A multi-enter trial, SPACE compared safety and efficacy of CASnd CEA in 1,183 randomized patients with symptomaticarotid artery stenosis (�70% by duplex ultrasonography,50% by NASCET criteria [1], or �70% by ECST criteria

3]). The 30-day rates of ipsilateral stroke or death were.84% for CAS and 6.34% for CEA (p value not significant)54). It is important to note that embolic protection was notequired and was only used in 27% of cases, though aubgroup analysis did not demonstrate a significant differ-nce between patients with embolic protection versus thoseithout. Despite these encouraging results, “SPACE failed

o prove the noninferiority of carotid-artery stenting” (54)tatistically. This is because the trial was halted more than00 patients shy of its goal enrollment of 1,900 patients ashe result of an interim analysis demonstrating that 2,500atients would be needed to reach significance given theesults up to that point. The Steering Committee acknowl-dged a “lack of funds” (54) to expand the trial to annrollment of 2,500 patients and therefore halted the trial.n essence, the study was underpowered to demonstrateoninferiority due to incorrect estimation of the anticipatedffect sizes. Still, although its a priori goals were notealized, the observed 0.51% difference in perioperativetroke or death between CAS and CEA was not statisticallyignificant and is well within the published differencesetween individuals, institutions, and variations of CEA.The results mentioned in the preceding text, although

hey were negative, were still quite encouraging to CASroponents. Unfortunately, a second multicenter, random-zed trial to assess the noninferiority of CAS versus CEA inatients with �60% stenosis, EVA-3S (Endarterectomyersus Angioplasty in Patients with Symptomatic Severearotid Stenosis), was ended after interim analysis (n �27) demonstrated a 30-day rate of any stroke or death to beignificantly higher in the CAS group (9.6%) than the CEAroup (3.9%) (p � 0.01) (55). Importantly, early in the trial,he use of embolic protection was not required. Patientsreated without embolic protection experienced a 25%0-day rate of stroke or death (5 of 20 patients), promptingrotocol changes by the EVA-3S safety committee. Addi-ionally, EVA-3S compared groups of physicians withnequal experience. Surgeons performing CEA had per-ormed at least 25 endarterectomies in the year before trialntry, yet endovascular physicians were certified after com-leting as few as 5 to 12 CAS procedures (5 CAS among at

east 35 stent procedures to supra-aortic vessels or 12 CAS).ndovascular physicians were also allowed to enroll studyatients while simultaneously undergoing training and cer-ification. Subgroup analysis based upon CAS physicianxperience demonstrated a 12.3% stroke and death ratemong endovascular physicians tutored in CAS during therial (55), compared with 7.1% among those tutored in CASuring their endovascular training and 10.5% among expe-

ienced CAS physicians. The resulting overall rate of strokeby Michael Jaff on March 16, 2008

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nd death (9.6%) is substantially higher than in otherandomized trials. Therefore, it is hard to accept such anlevated complication rate as representative of the practicef CAS in general. It is more likely that EVA-3S empha-izes the importance of embolic protection as well asigorous training and credentialing for CAS physicians. Themplied importance in EVA-3S of embolic protection haseen further supported by numerous radiologic studiesxamining the frequency of (mostly small, asymptomatic)schemic (DWI [diffusion-weighted imaging]) lesions onost-operative magnetic resonance imaging. These studiesave demonstrated the following: a reduction in the fre-uency of DWI lesions with distal embolic protection (49%s. 67%) (48) and fewer DWI lesions after CEA than CAS11.6% vs. 42.6%, no significant clinical difference) withurrent embolic protection devices (56), and a low frequencyf DWI lesions with more recent embolic protection de-ices, such as the NeuroProtection System (W.L. Gore &ssociates, Flagstaff, Arizona) (57), at a rate not signifi-

antly different from that incurred by diagnostic cerebralngiography alone (18.2% vs. 11.5%) (58).

Carotid registries (CABERNET [Carotid Artery Revascu-arization using the Boston Scientific FilterWire EX/EZ andhe EndoTex NexStent], ARCHeR [ACCULINK for Revas-ularization of Carotids in High-Risk patients], CREATECarotid Revascularization with ev3 Arterial Technology Evo-ution], CAPTURE [Carotid Acculink/Accunet Post Ap-roval Trial to Uncover Unanticipated or Rare Events],EACH [Boston Scientific EPI: A Carotid Stenting Trial forigh-Risk Surgical Patients], CASES-PMS [Carotid Artery

tenting with Emboli protection Surveillance—Post Market-ng Study], and ALKK [Arbeitsgemeinschaft Leitende Kardi-logische Krankenhausarzte]) are nonrandomized outcomeecords for symptomatic and asymptomatic high-risk CASatients. Although registries do not provide direct comparisonata, they do help establish true adverse event rates in high-riskAS patients and are a crucial component in improving ournderstanding concerning the risks of CAS. The collaboratorsf CABERNET (n � 462 patients) found a 3.9% 30-day ratef stroke or death (59), whereas the investigators of ARCHeRn � 581 patients) found a 30-day stroke or death rate of 6.9%s well as a 1-year composite outcome (30-day rate of MI,troke, or death plus the 1-year rate of ipsilateral stroke) of.6% (60). The CREATE registry (n � 419 patients) dem-nstrated a 6.2% 30-day rate of MI, stroke, and death (61).he CAPTURE registry (n � 3,500) determined that post-AS incidence of stroke, MI, and death was 6.3% for patients

reated with the Acculink/Accunet CAS system (Abbott Vas-ular, Santa Clara, California), as well as a rate of major stroker death of 2.9% (62,63). The BEACH investigators (n � 747atients) found a 30-day MI, stroke, or death rate of 5.8% (64).hese results were similar to those in the CASES-PMS

egistry (5.0%), which examined the use of distal protection byndovascular carotid surgeons who either had previous experi-nce with the device (Angioguard XP, Cordis Endovascular,

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,493) (65). Under these rigorous conditions, the 30-day majordverse event rate did not vary significantly between symptom-tic and asymptomatic patients and among physicians withigh- and low-volume or differing level of experience with thepecific distal protection device. The German ALKK registryn � 1,888 patients), which included patients with standardisk, demonstrated an in-hospital death and stroke rate of 3.8%66). Interestingly, when this risk was stratified by time, thenvestigators saw improvement from 6.3% in 1996 to 1.9% in004 (p � 0.021). Continued effort to maintain rigorousegistries like the above are critical to our eventual understand-ng of appropriate patient selection and procedural risks.

urrent Trials

he 2 major ongoing, randomized trials of CAS versusEA are CREST (Carotid Revascularization Endarterec-

omy versus Stent Trial) and ICSS (International Carotidtenting Study). The CREST trial is an ongoing, Nationalnstitutes of Health-funded, multicenter randomized trialeeking to enroll 2,500 patients with �50% symptomaticarotid stenosis or �70% asymptomatic stenosis for ran-omization to CEA or CAS. Primary end points includeeath, stroke, or MI at 30 days, and ipsilateral stroke within0 days. The CREST trial maintains a rigorous credential-ng phase for CAS providers (67), requiring up to 20

onitored procedures. During its lead-in phase, CRESTemonstrated a 4.6% 30-day stroke and death rate, withI, stroke, and death rates of 5.7% for symptomatic

atients and 3.5% for asymptomatic patients. Similar strokend death rates were observed for both men and women68), as well as those treated with or without embolicrotection (69). However, patients �80 years (70,71) expe-ienced a 30-day stroke and death rate of 12.1%, signifi-antly higher than for patients age 60 to 69 years (1.3%) and0 to 79 years (5.3%) (p � 0.0006) (70).The ICSS study resulted from the favorable results of

AVATAS and is also known as CAVATAS-2 (72). It ismultinational prospective trial randomizing symptomatic

atients equally suited for CAS or CEA. Additionally,essons learned from EVA-3S are being applied. Atten-ance at a CAS training course is required, as well asandatory proctoring for centers with limited experience

dmitted to the trial on a probationary status. Further,mbolic protection is recommended whenever the endovas-ular physician believes a protection device can be safelyeployed.An additional ongoing study is ACT I (Asymptomatic

arotid Stenosis, Stenting versus Endarterectomy Trial), aandomized trial of low-risk patients with asymptomatic0% to 99% carotid stenosis at multiple centers across Northmerica (73,74). The primary outcomes will be 30-day MI,

troke, and death rates and 5-year stroke-free survival. TheACIT (Transatlantic Asymptomatic Carotid Interventionrial) will randomize standard- and high-risk patients with

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ptimal medical therapy only (antiplatelet, antilipidemic,ntihypertensive, strict diabetes control, and smoking ces-ation), optimal medical therapy plus CEA, or optimaledical therapy plus CAS with embolic protection (75,76).lanned enrollment is 2,400 patients with a primary endoint of stroke and death occurrence at 3 years. Secondarynd points include rates of TIA and MI, economic cost,uality-of-life analysis, neurocognitive function, and carotidestenosis. Continued effort and the eventual completion ofhese trials will improve our understanding of the relativendications and contraindications of CAS and CEA.

ptimal Treatment Selection

iven the existence of surgical and endovascular therapiesor patients with carotid stenosis, optimal treatment selec-ion for each given patient will be the eventual method byhich the lowest morbidity rates with the most favorableutcomes are achieved. Fundamental to treatment selections an understanding of the demographics used to categorizeatients as high risk. High-risk demographics are previouslyefined in large surgical studies, such as NASCET (1) andCAS (5). These demographic criteria include:

Anatomical: 1) restenosis after CEA; 2) contralateralocclusion; 3) previous neck radiation or surgery; 4)surgically inaccessible lesions (e.g., located above theC-2 level, below the clavicle); 5) neck immobility; 6)tracheostomy; 7) contralateral laryngeal palsy; 8) bi-lateral severe stenotic lesions requiring treatment; and9) severe intracranial stenosis.

Medical comorbidities: 1) unstable angina; 2) poorcardiac ejection fraction; 3) congestive heart failure; 4)planned coronary artery bypass operation; 5) obstruc-tive pulmonary disease; and 6) advanced age (�75 or80 years, depending on the trial).

Given the continually mounting evidence, it appearsppropriate to offer CAS over CEA to all patientseeting the above high-risk categorizations, symptom-

tic or asymptomatic. However, whether patients do oro not strictly meet the above criteria, other characteris-ics need to be taken into account. For instance, patientsith heavily calcified plaques, a complex aortic arch,

xcessively tortuous vessels, or internal carotid arteriesith lumen diameters smaller than 3 mm are likely better

erved with endarterectomy (77– 85). This is becauseeavily calcified plaques often result in insufficient endo-ascular revascularization secondary to their being refrac-ory to balloon remodeling; loops and significant vesselortuosity make stable guide catheter placement as well aslter and stent deployment excessively difficult, and

umen diameters smaller than 3 mm do not safely

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onclusions

arotid artery stenting is continually developing into a safernd more efficacious therapy for extracranial carotid arterytenosis. The greater weight of the evidence, as confirmed inCochrane review (86), suggests no significant difference

etween CAS and CEA. However, CAS is still a burgeon-ng technology with many questions still needing to benswered. Future clinical research should address many ofhese questions. As we move towards the future, theuestion posed should now be “what is the optimal treat-ent for carotid artery stenosis in this patient?” not “what is

he optimal treatment for carotid artery stenosis?” Endovas-ular physicians must rigorously apply the lessons learnedrom previous well-designed trials to avoid treating patientsho are at higher risk for complications with CAS. Con-

inued enrollment in rigorously randomized trials such asREST will provide a great deal of insight into suchatient-specific risk factors. The use of CAS and CEA asomplementary therapies, while optimizing current medicalreatments, will provide the greatest likelihood of minimiz-ng poor patient outcomes.

eprint requests and correspondence: Dr. Elad I. Levy, Univer-ity at Buffalo Neurosurgery, Millard Fillmore Gates Hospital, 3ates Circle, Buffalo New York 14209. E-mail: elevy@buffns.com.

EFERENCES

1. North American Symptomatic Carotid Endarterectomy Trial Collab-orators. Beneficial effect of carotid endarterectomy in symptomaticpatients with high-grade carotid stenosis. N Engl J Med 1991;325:445–53.

2. Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotidendarterectomy in patients with symptomatic moderate or severestenosis. North American Symptomatic Carotid Endarterectomy TrialCollaborators. N Engl J Med 1998;339:1415–25.

3. European Carotid Surgery Trialists’ Collaborative Group. MRCEuropean Carotid Surgery trial: interim results for symptomaticpatients with severe (70–99%) or with mild (0–29%) carotid stenosis.Lancet 1991;337:1235–43.

4. MRC European Carotid Surgery Trialists. Randomised trial of end-arterectomy for recently symptomatic carotid stenosis: final results ofthe MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–87.

5. Executive Committee for the Asymptomatic Carotid AtherosclerosisStudy. Endarterectomy for asymptomatic carotid artery stenosis.JAMA 1995;273:1421–8.

6. Halliday A, Mansfield A, Marro J, et al. Prevention of disabling andfatal strokes by successful carotid endarterectomy in patients withoutrecent neurological symptoms: randomised controlled trial. Lancet2004;363:1491–502.

7. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention ofstroke in patients with ischemic stroke or transient ischemic attack: astatement for healthcare professionals from the American HeartAssociation/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Interven-tion: the American Academy of Neurology affirms the value of thisguideline. Stroke 2006;37:577–617.

8. Wennberg DE, Lucas FL, Birkmeyer JD, Bredenberg CE, Fisher ES.Variation in carotid endarterectomy mortality in the Medicare popu-lation: trial hospitals, volume, and patient characteristics. JAMA1998;279:1278–81.

9. Halm EA, Chassin MR, Tuhrim S, et al. Revisiting the appropriate-ness of carotid endarterectomy. Stroke 2003;34:1464–71.

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doi:10.1016/j.jacc.2007.10.052 2008;51;979-985 J. Am. Coll. Cardiol.

and L. Nelson Hopkins Elad I. Levy, J. Mocco, Rodney M. Samuelson, Robert D. Ecker, Babak S. Jahromi,

Optimal Treatment of Carotid Artery Disease

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