Diagnosis and management of carotid arte

Diagnosis and Management of Carotid Artery Disease: The Role ofCarotid Artery Stenting Scope of the Problem: Prevalence and Epidemiology 499 Diagnosis of Carotid Artery Stenosis 502 Surg

Diagnosis and Management of Carotid Artery Disease: The Role of

Carotid Artery Stenting

Suhail Allaqaband, MDCardiovascular Disease Fellow University of Wisconsin Medical School Milwaukee, WisconsinRamagopal J Tumuluri, MDCardiovascular Disease Fellow University of Wisconsin Medical School Milwaukee, WisconsinAnil Kumar Goel, MDCardiovascular Disease Fellow University of Wisconsin Medical School Milwaukee, WisconsinKiran Kashyap, MDInterventional Cardiology Fellow University of Wisconsin Medical School Milwaukee WisconsinAnjan Gupta, MD, FACCAssociate Director Cardiovascular Disease Fellowship Training Program

and Clinical Instructor of Medicine University of Wisconsin Medical School Milwaukee, WisconsinTanvir K Bajwa, MD, FACC, FSCAIDirector of the Peripheral Vascular Disease and Cardiac Catheterization Laboratories

Milwaukee Heart Institute of Sinai Samaritan Medical Center

and Clinical Associate Professor of Medicine University of Wisconsin Medical School Milwaukee, Wisconsin

Current Problems in

Volume 26 Number 8 August 2001

Current Problems in

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Diagnosis and Management of Carotid Artery Disease: The Role of

Carotid Artery Stenting

Scope of the Problem: Prevalence and Epidemiology 499

Diagnosis of Carotid Artery Stenosis 502

Surgical Management of Carotid Artery Disease 508

Nonsurgical Treatment of Carotid Artery Stenosis 513Percutaneous Balloon Angioplasty for Carotid Artery Disease 513

Simultaneous Carotid and Coronary Artery Interventions 519Carotid Artery Stenosis With Contralateral Occlusion 520Carotid Artery Stenosis with Prior Radiation Exposure 521Carotid Artery Stenting in Restenotic Lesions after Endarterectomy 522Carotid Artery Stenting for Bilateral Carotid Artery Stenosis 527Carotid Artery Stenting for Surgically Inaccessible Lesions 531

Current Problems in

Carotid Artery Stenting for Takayasu’s Arteritis 532Carotid Artery Stenting In Octogenarians 534Complications Associated with Extracranial Carotid Artery Intervention 536

New Therapies and Devices in Carotid Artery Stenting 537

Use of Glycoprotein IIb/IIIa Receptor Inhibitor 539

Approaches and Devices for Cerebral Protection 541

Filtration Device Placed Distal to the Lesion 543

Carotid Artery Stenting: Ongoing and Future Trials 544

In the August issue of Current Problems in Cardiology, Dr Bajwa and

his colleagues from the Milwaukee Heart Institute and the University ofWisconsin Medical School in Milwaukee provide a comprehensive dis-cussion of the role of carotid artery stenting in the management of patientswith carotid artery disease They discussed the noninvasive and invasivedemonstration of carotid artery disease and the treatment of patients withthis relatively common clinical problem by medical therapy, surgicalmanagement, and percutaneous catheterization techniques

Dr Bajwa and his colleagues have had considerable experience in ing large numbers of patients with carotid artery stenting, and they pro-vide an extremely informative discussion of the indications, contraindica-tions, and results of coronary artery stenting in various groups of low- andhigh-risk patients

treat-I am grateful to Drs Allaqaband, Tumuluri, Goel, Kashyap, Gupta, andBajwa for their contribution to this month’s monograph

Robert A O’Rourke, MD, FACC, MACP

Editor in Chief

Dr Tanvir Bajwa is Director of thePeripheral Vascular Disease and Car-diac Catheterization Laboratories atthe Milwaukee Hear t Institute of SinaiSamaritan Medical Center in Milwau-kee He is a clinical associate profes-sor of medicine at the University ofWisconsin Medical School—Milwau-kee clinical campus and is currently involved in the SAPPHIRE andARCHER trials of carotid ar ter y stenting.

Dr Anjan Gupta is the associate tor of the cardiovascular disease fel-lowship training program and a clinicalinstructor of medicine at the Univer-sity of Wisconsin Medical School—Milwaukee clinical campus

direc-Dr Suhail Allaqaband is a cular disease fellow at the University

cardiovas-of Wisconsin Medical waukee clinical campus

School—Mil-Dr Anil Goel is a cardiovascular ease fellow at the University of Wis-consin Medical School—Milwaukeeclinical campus

dis-Dr Ramagopal Tumuluri is a vascular disease fellow at the Univer-sity of Wisconsin Medical School—Milwaukee clinical campus

cardio-Dr Kiran Kashyap is a four th-yearinter ventional cardiology fellow at theUniversity of Wisconsin MedicalSchool—Milwaukee clinical campus

Diagnosis and Management of Carotid Artery Disease: The Role of

Carotid Artery Stenting

Scope of the Problem: Prevalence and Epidemiology

very year in the United States, stroke kills 160,000 people andaccounts for 1 of every 15 deaths, making it the third leadingcause of death behind heart disease and cancer.1Each year, about600,000 have a new or recurrent stroke, of which approximately 500,000are first attacks and 100,000 are recurrent attacks

Stroke strikes men and women equally, although at all ages, morewomen than men die of stroke On the basis of the National Heart, Lung,and Blood Institute’s Atherosclerosis Risk in Communities study’s2age-adjusted annual incidence rate for stroke, it affects 1.78 white men, 4.44black men, 1.24 white women, and 3.10 black women in every 1000 eachyear Overall, the risk of a first stroke is 38% greater for black people thanfor white people.3

Pathologic Study

In the Framingham Heart Study, the most common type of stroke wasatherosclerotic brain infarction, which accounted for 61% of all strokes,excluding transient ischemic attacks (TIAs) In the National Heart, Lung,and Blood Institute’s Atherosclerosis Risk in Communities study,283% ofall strokes were ischemic, of which 38% were lacunar, 14% were throm-boembolic, and the remainder were large artery strokes

In the 1950s, most brain infarctions were attributed to intracranial rial occlusion.4Over the years, Fisher et al have studied the pathophysio-logic condition and clinical presentation of strokes, leading to greaterunderstanding of the importance of intracranial arterial disease Theyidentified the most common sites as the carotid bifurcation, the internalcarotid arteries, and the proximal vertebral arteries.5,6

arte-Clinical Presentation The clinical manifestations of carotid artery

dis-ease are carotid bruit and symptoms caused by cerebral ischemia; ever, a patient may have significant carotid artery stenosis without anysigns or symptoms

how-Carotid bruit Although cervical bruit is an important sign of carotid

artery disease, in a series of 331 patients referred to a neurology clinic in

E

which half had a carotid bruit, only 37% had a high-grade lesion oncarotid artery duplex ultrasound scanning.7 In an analysis of patientsenrolled in the North American Symptomatic Carotid EndarterectomyTrial (NASCET),8findings of a focal ipsilateral carotid bruit had a sensi-tivity of 63% and specificity of 61% for high-grade stenosis, with a higheryield in patients with symptoms, 75% of whom had moderate-to-severestenosis on diagnostic testing.

The Framingham Heart Study showed that in symptom-free patients acarotid bruit doubled the risk of stroke.9 In another population-basedstudy, in patients who had a bruit, the annual rate for all primary vascularevents was 11% if the stenosis was >50% and only 4.2% if the stenosiswas <50% The annual rate for unheralded stroke was 1.4% in patientswho had stenosis <80% and 4.2% in those who had stenosis >80%.10

Cerebral ischemia or embolization Although patients who have carotid

artery disease can be diagnosed clinically with TIAs (which generally lastfor <24 hours), reversible ischemic deficits (which last from 1 day to 3weeks), stroke, monocular blindness, amaurosis fugax, or aphasia, none

of these is specific for carotid artery disease After the diagnosis of TIA,the patient’s risk of first stroke is 8% in the first month, 12% in the firstyear, and as much as 30% within 5 years.11

Symptoms Increase Risk

In studies that document the risk of stroke in carotid artery disease, therisk for symptomatic carotid artery stenosis (eg, TIAs, nascent monocularblindness, and nondisabling strokes) and for asymptomatic carotid arterystenosis is proportional to the severity of the disease In patients whosestenosis was <75%, the annual rate of stroke was 1.3%, almost tripling to3.3% in those whose stenosis was >75% In a symptom-free populationwhose stenoses were >75%, the annual rate of ipsilateral stroke was2.5%.12

The risk of stroke in patients who have TIAs related to severe carotidartery stenosis is approximately 10% within the first year and 30% to 35%

at the end of 5 years.13In the European Carotid Surgery Trial (ESCT),14the 3-year stroke risk for symptom-free patients who had mild-to-moderate stenosis and were on medical therapy was 2.1%, increasing to9.8% in patients who had 80% to 89% stenosis and to 14.4% in patientswho had 90% to 99% stenosis

NASCET15showed that the 2-year risk for ipsilateral stroke was 26%and 28% for stroke in any territory; it was 28% and 32% for stroke ordeath related to a high-grade stenosis while on medical treatment In thesame study, across all degrees of severity, in patients who were randomly

selected to receive medical treatment alone, the risk of ischemic strokefrom ipsilateral carotid artery stenosis was 7.9% at 2 years and 12.4% at

5 years

Risk Factors Atherogenesis of the carotid arteries is an insidious

process marked by carotid artery wall thickness and reduced ity.16 Of the many risk factors (discussed below) that contribute to andcause atherosclerosis to propagate, some are modifiable (eg, controlled oreliminated through lifestyle changes or by medical intervention), andsome are not, because they are immutable characteristics inherent in aparticular individual.17

distensibil-Nonmodifiable risk factors It goes without saying that age, sex, and

race or ethnicity are nonmodifiable risk factors In adults, the risk ofstroke doubles for each decade of life, and men are at greater risk thanwomen The incidence of stroke is higher in black men.18-20The NorthernManhattan Stroke Study is a new report that America’s rapidly increasingpopulation of Hispanic-Americans also has an increased incidence ofstroke.20

Modifiable risk factors The most eminently treatable causes of

athero-genesis are as follow:

Hypertension Hypertension has been shown to be a major risk factor

for cardiovascular disease, most notably in the Framingham Heart Study,

in which the risk of disease clearly increased as a direct function of thedegree of systolic and diastolic hypertension.21 Analysis of various hyper-tension trials has shown that isolated systolic hypertension is stronglyassociated with the degree and progression of carotid artery stenosis andthat a reduction of 6 to 7 mm Hg in diastolic blood pressure decreases the5-year incidence of stroke by 42%.22,23

Hyperlipidemia Over the years, we have learned that the degree and

progression of atherogenesis is markedly affected by cholesterol levels,especially by elevated levels of low-density lipoprotein (LDL) and byhigh ratios of LDL to high-density lipoprotein; we have also learned thatreducing LDL and total cholesterol decreases carotid artery plaque andstenosis.24,25

Diabetes mellitus For both type 1 and type 2 diabetes mellitus,

inten-sive treatment aimed at reducing blood glucose to near-normal levels cansubstantially reduce the risk of such microvascular complications asretinopathy and neuropathy, but this treatment has conclusively reducedsuch macrovascular complications as stroke.26-29

Smoking Cigarette smoking is an unquestionable risk factor for stroke,

perhaps because it increases the risk of atherogenesis.30,31 A subgroupanalysis in the Cardiovascular Health Study showed that, as smoking

increased, so did significant internal and common carotid artery wallthickening: of those patients smoking at the time of the study, 24% had anundiagnosed stenosis contrasted with 20% in former smokers and 16% in

those who had never smoked (P = 001) The prevalence of a clinically

significant (>50%) internal carotid artery stenosis increased from 4.4% inthose who had never smoked to 7.3% in former smokers and 9.5% in cur-

rent smokers (P < 0001).

Inflammation and chronic infection Recent evidence suggests that

inflammation and systemic infection play a role in atherosclerosis.32In aclinical study of asymptomatic carotid artery atherosclerosis, it was found

that Chlamydia pneumonia strain TWAR had a significant cross-sectional

association This organism may be a contributor to the pathogenesis ofatherogenesis in carotid artery disease.33Patients who have more than one

of these risk factors multiply their chances for development of severecarotid artery stenosis.34

Diagnosis of Carotid Artery Stenosis

Diagnosis of carotid artery disease begins with careful history-takingand thorough physical examination, followed as appropriate by one ormore of the diagnostic tests described below Currently available modali-ties that help confirm a diagnosis of carotid artery disease include bothinvasive tests, such as cerebral angiography, and noninvasive tests, such ascarotid duplex ultrasonography (CDUS) and magnetic resonance angiog-raphy (MRA)

Noninvasive Tests

Carotid Artery Duplex Ultrasonography Combining B-mode

ultra-sound imaging and Doppler ultrasonography to detect carotid arterystenosis, CDUS is currently the most widely used noninvasive test forcarotid artery stenosis B-mode ultrasound scanning typically displays, inreal time, a longitudinal section of the carotid artery, including the com-mon carotid artery, the bifurcation of the carotid artery, and the internaland external carotid arteries Doppler ultrasonography helps to evaluateflow in the carotid artery and thus, on the basis of predetermined parame-ters of flow velocity, helps to estimate the degree of stenosis

CDUS is not only safe because it is noninvasive, but it is also portableand inexpensive Moreover, CDUS can be used to study the composition

of the atherosclerotic plaque

The sensitivity, specificity, and overall accuracy of CDUS are welldefined in the literature Suwanwela et al35showed that findings of a peaksystolic velocity of >440 cm/s had a sensitivity of 58%, an end-diastolic

velocity of >155 cm/s had a sensitivity of 63%, and a carotid artery index(calculated as peak internal carotid artery velocity ÷ common carotidartery velocity) of >10 had a sensitivity of 30%; all 3 measurements had

a specificity of 100% Recently, Huston et al36compared CDUS with ventional angiography in 1218 carotid arteries For patients who had aninternal carotid artery (ICA) stenosis of 70% to 99%, findings of a peaksystolic velocity of >230 cm/s had a sensitivity of 86.4%, a specificity of90.1%, a positive predictive value of 82.7%, and a negative predictivevalue of 92.3% An end-diastolic velocity of >70 cm/s and a carotid arteryindex of >3.2 yielded similar values

con-However, CDUS has limitations It is not as precise in determiningstenoses of 50% or less It can evaluate the extracranial portion of thecarotid arteries but not the intracranial cerebral circulation With CDUS

it may be difficult to distinguish between an occluded artery and a veryhigh–grade stenosis In fact, the risk of misclassifying a high-gradestenosis as occluded has been reported to be as high as 14%.37Finally,the accuracy of CDUS depends highly on the experience of the ultra-sonographer, and there may be considerable variation between laborato-ries (Fig 1)

Magnetic Resonance Angiography MRA is becoming a valuable tool

in the evaluation of carotid artery stenosis The two most commonly used

FIG 1 Carotid duplex ultrasound scan reveals peak systolic velocity of 600 cm/s indicating high-grade stenosis in right ICA.

methods to visualize vascular structures include phase contrast MRA andeither 2- or 3-dimensional time-of-flight (TOF) MRA For carotid arter-ies, the TOF method is used most often.

An important advantage of MRA is that one examination can visualizethe full extent of the carotid circulation from its origin to the intracranialvessels A reproducible MRA image of the carotid arteries has a 75% to90% sensitivity of detecting carotid artery stenosis of 70% to 99%.38-40MRA results are less reliable when blood flow is slow, turbulent, orabsent, and, as a result, the degree of stenosis is consistently overesti-mated, reducing specificity

However, in using the TOF method, Huston et al41have reported betteraccuracy because the method is more sensitive to slow blood flow Withthe higher resolution of 3-dimensional TOF, sensitivity improves greatlyfor differentiating between an occluded artery and one with a high-gradelesion MRA is less operator dependent than CDUS but considerablymore expensive and not practical in critically ill patients, in patients whohave implants (such as pacemakers) that are metallic or have metalliccomponents, or in claustrophobic patients

Other Noninvasive Tests

Computed Tomographic Angiography Computed tomographic

angiog-raphy can obtain images of both cervical and intracranial vasculature; itscapability of distinguishing occlusions from high-grade lesions and itssensitivity and specificity for diagnosing high-grade carotid arterystenoses are comparable to those of CDUS.42Unlike CDUS, the need touse contrast media means that it may be contraindicated in patients whohave renal insufficiency

Transcranial Doppler scanning Transcranial Doppler scanning can be

used in conjunction with CDUS to identify intracranial collateral vesselflow patterns and to evaluate the hemodynamic significance of extracra-nial carotid artery stenoses

Power Doppler imaging Power Doppler imaging is a new sonographic

technique that has vascular applications because it can clearly defineintravascular surfaces, and it seems to be highly sensitive when there islow blood flow In a study by Steinke et al,43more power Doppler imag-ing displays of the intravascular lumen were rated either “good” or

“excellent” than displays by color-flow Doppler imaging (92% vs 79%)

Invasive Tests

Conventional Contrast Angiography Since its introduction,

conven-tional contrast angiography (CCA) has been the gold standard for

obtain-ing images of the carotid arteries Recent improvements, such as use ofsmaller and softer catheters, the Seldinger technique, and the transfemoralapproach, have reduced its complications and have significantly improvedimage resolution.

All major carotid endarterectomy (CEA) trials have relied on CCA to tify candidates because this method visualizes both the extracranial carotidarteries and the intracranial vasculature, including branches of the circle ofWillis It also visualizes vertebrobasilar circulation and provides informationabout plaque structure, plaque ulceration, and plaque dissection

iden-Its disadvantage is invasiveness NASCET and other prospective studiesreport a 4% risk of all neurologic complications and a 1% risk of a majorstroke or death.44,45

Another limitation is the lack of uniformity in measuring carotid arterystenoses This problem became evident in the two major randomized tri-als of CEA that used two different methods to measure carotid arterystenosis by use of CCA (Fig 2)

NASCET compared the measurement of the residual lumen diameter atthe most stenotic portion of the vessel with that of the lumen diameter in

a normal portion of the ICA distal to the stenosis.46 On the other hand, theEuropean Carotid Surgery Trial (ECST) measured this most stenotic por-tion of the vessel against the diameter of the carotid bulb, which was esti-mated visually by presuming that the unseen carotid artery had a normal

FIG 2 Drawing compares NASCET (left) and ECST (right) methods of measuring degree of carotid artery

stenosis from carotid angiogram.

diameter Consequently, a diagnosis with the NASCET method wouldindicate lesser severity than one with the ECST method For example, a50% stenosis by the NASCET method would be classified as 70% to 80%

by the ECST method.47 The NASCET method is generally consideredmore reliable because it is generally considered more accurate, is easilylearned, and is reproducible with little interobserver variability

Choice of Imaging Study

Although invasive and risky, CCA is the gold standard for diagnosingcarotid artery disease However, because of its associated morbidity anddeath, CCA should be preceded by noninvasive studies

A number of studies have compared the sensitivity, specificity, andaccuracy of CCA with that of CDUS, MRA, and computed tomographyangiography In a study of results in 42 patients, Riles et al48reported thatMRA correlated exactly with CCA in 52% of patients and that CDUS cor-related with CCA in 65% of patients Both MRA and CDUS yieldedexaggerated estimates of the degree of stenosis compared with CCA Themost egregious errors were 3 readings of occlusions on MRA in vesselsfound to be patent on CCA

Serfaty et al49 assessed the accuracy of 3-dimensional enhanced MRA used alone or in combination with CDUS for evaluatingextracranial carotid arteries They found that MRA alone had a sensitivity

gadolinium-of 94% and a specificity gadolinium-of 86% for detecting carotid artery stenosis gadolinium-of70% to 99%.49When combined with CDUS, MRA had 100% sensitivityand specificity In a metaanalysis of all studies involving noninvasive testsfor carotid artery stenosis that was based only on articles where the non-invasive tests used CCA as the reference standard, Blakeley et al50foundthat CDUS and MRA had roughly equal sensitivity (82% to 86%) andspecificity (98%) for carotid artery stenosis of 70% or more They foundthat B-mode ultrasonography was poorer for detecting carotid arterystenoses and that supraorbital Doppler scanning had a sensitivity of 86%and a specificity of 90%

Kent et al51assessed the cost-effectiveness of 4 diagnostic strategies forpreoperative evaluation of patients with symptoms: (1) CDUS, (2) MRA,(3) CCA, and (4) CDUS + MRA supplemented with CCA for disparateresults They found that the latter had the lowest long-term morbidity andmortality rates and a favorable cost-effectiveness ratio that resulted in

$22,400 per quality-adjusted year of life gained

As a review of the literature shows, CCA, although accurate, carries afinite risk of morbidity and death For reliable preoperative evaluation ofeligibility for CEA, current literature supports the strategy of preoperative

evaluation with CDUS plus MRA supplemented by CCA in patients whohave equivocal or disparate results However, this strategy can be recom-mended to patients only in centers with adequate experience and expertise

in both CDUS and MRA Table 1 compares these treatment methods

Medical Therapy

Antiplatelet Agents

Aspirin is the most widely studied and, until recently, the only drug usedbroadly for this purpose Clinical trial results now indicate that ticlopi-dine, clopidogrel, and dipyridamole are also effective in preventing strokeand other vascular events in patients who have cerebrovasular disease

In a major metaanalysis52that assessed the effects of antiplatelet agents

in patients with atherosclerosis, a combined 73,247 patients at high riskwho had been in trials of long-term antiplatelet therapy (>30 days) wereanalyzed for composite outcomes of stroke, death, and nonfatal stroke.The overall reduction in odds for stroke or vascular death was 27%, ofwhich 25% was attributable to aspirin

The odds of a nonfatal stroke were reduced by 31%, and the odds ofreduction in stroke or TIA was 22% In their mini metaanalysis (10 trials),Algre and van Gijn53concluded that in patients who had a prior stroke orTIA, aspirin alone reduced the odds of stroke by 16%

Two large trials, the Canadian American Ticlopidine Study54 and theTiclopidine Aspirin Stroke Study,55evaluated the efficacy of ticlopidine inpatients who had cerebrovascular disease At 3 years the relative risk ofstroke was reduced to 23.3% Although effective for stroke prevention, itsusefulness is limited by its side effects, especially neutropenia

The CAPRIE Trial56 assessed the relative efficacy of clopidogrel (75mg/d) and aspirin (325 mg/d) in reducing the risk of composite outcomes

of ischemic stroke, myocardial infarction (MI), or vascular death In thestroke subgroup (6000 patients), intention-to treat-analysis showed asmall relative reduction of 8.7% for these events in favor of clopidogrel

TABLE 1 Comparison of CCA, CDUS, and MRA

Absolute and relative None Metal implants, claustrophobia Renal dysfunction poor

CHF

Dipyridamole has been studied in 10 different trials, where it was used

as monotherapy Combined analysis showed a 23% odds reduction in thestroke When the combination of aspirin and dipyridamole was evaluated,the European Stroke Prevention Study57 reported a 33% reduction forstroke, and the European Stroke Prevention Study–258reported a 21.3%reduction, both of which were statistically significant The combination ofaspirin and extended release dipyridamole is well tolerated and provides

a useful alternative to aspirin

Anticoagulants

No large, well-designed, randomized trial has yielded data to adequatelyassess the efficacy of oral anticoagulants in the secondary prevention ofatherothrombotic non-heart–related strokes.59At present, only one largerandomized trial60has compared intensive anticoagulation (internationalnormalized ratio 3 to 4.5) with aspirin (30 mg/d) in patients who haveminor strokes and TIAs, but it was terminated prematurely because of thehigh incidence of hemorrhaging in the anticoagulation group The large,ongoing Warfarin Aspirin Recurrence Study is comparing a lower targetinternational normalized ratio (1.4 to 2.8) with aspirin (325 mg/d) inpatients who have had a recent atherothrombotic stroke

There may be some patients who are specific atherothrombotic subtypesthat respond favorably to oral anticoagulants A nonrandomized retro-spective study61found that patients with symptomatic intracranial steno-sis had a lower stroke rate when they took warfarin rather than aspirin.The randomized Warfarin Aspirin Symptomatic Intracranial DiseaseStudy is currently underway to study these preliminary results

Surgical Management of Carotid Artery Disease

Since 1954, when CEA was first performed to prevent ischemic strokesfrom carotid artery stenosis, the number of procedures rose annually inthe United States to a peak of 107,000 in 1985, until findings reported inthe extracranial-intracranial arterial bypass (EC-IC) study about lack ofbenefit from the EC-IC bypass procedure created uncertainties aboutCEA, leading to a significant decline.62 Large randomized trials wereplanned to address these uncertainties

Trials of CEA in Patients with Symptoms

As shown in Table 2, the two major trials of CEA14,15 in patients withsymptoms were the NASCET and the ECST Ethical considerations termi-nated the Veterans Administration Cooperative Trial early in 1991, whenNASCET and ECST demonstrated the overwhelming benefit from surgery.63

Patients with mild stenosis in the ECST Trial had little risk of ipsilateralischemic stroke; the possible benefits of CEA were small and were out-weighed by the early risks The 30-day incidence of death or stroke in thepatients with a severe stenosis was 7.5% in the CEA group.

NASCET, a randomized, controlled trial from 50 centers in the UnitedStates and Canada, assigned patients to one of two arms for either CEA

or best medical management, with 2 categories used for carotid arterystenosis severity, that is, moderate (30% to 69%) and severe (70% to99%) The severe stenosis arm, which enrolled 659 patients, was prema-

turely terminated because of the overwhelming (71%) risk reduction (P <

In the 50% to 69% stenosis subgroup, a marginal benefit was noted infavor of surgery, that is, a lower risk (15.7%) for ipsilateral stroke at 5-

year follow-up than for the medical group (22.2%) (P = 045) Patients

whose stenosis was <50% did not benefit from surgery

Taken together, these three trials provide convincing evidence favoringCEA to treat patients who have symptomatic high-grade stenosis (>70%).Its benefit is marginal in treating patients who have 50% to 69% stenosis,and it has no benefit in patients who have <50% stenosis Benefits of CEAwere realized early after surgery, lasted over time, and were independent

of risk factors other than severity of stenosis

Caveats Because CEA was performed by experienced surgeons, a

major determinant of benefit was low surgical risk, which should not beexpected with regard to patients at high risk for stenosis It is difficult to

TABLE 2 Major trials of CEA in patients with symptoms

Risk of stroke during follow-up (yrs)

Degree of ipsilateral carotid

ESCT 2518 All degrees CEA vs medical treatment with 2.8% (3) * 16.8% *

aspirin

VA Cooperative 193 50% CEA + medical treatment vs 7.7% (11.9 mo) 19.4%

* In patients who have 70% to 90% carotid ar ter y stenosis.

(y)

generalize from these results in specific cohorts to the general lation.

popu-Symptom-free Patients

The clinical strategy of watchful waiting for symptoms to developbefore intervening aggressively is questionable in patients who have ath-erosclerosis because it is a systemic disease that can be asymptomaticuntil its late stages, by which time there may be such complications asstroke, MI, or sudden death Studies that addressed the question of usingCEA to treat patients who have ipsilateral asymptomatic atherosclerosishave been listed in Table 3.64-66

Exclusion criteria were similar in Asymptomatic Carotid sis Study (ACAS), Veterans Administration Cooperative Study (VAAST),and Carotid Artery Stenosis with Asymptomatic Narrowing: OperationVersus Aspirin (CASANOVA) trial, that is, severe medical comorbiditiesand conditions that may affect stroke outcome, such as seizures, demen-tia, atrial fibrillation, and valvular disease No patients in the study wereincluded who had ipsilateral symptoms, although patients who had con-tralateral symptoms were enrolled in ACAS and VAAST

Atherosclero-In CASANOVA, more than half of those in the medical treatment groupunderwent CEA during 3-year follow-up It should be noted that thisstudy’s unusual design limited its statistical validity, which reported nodifference in the end points of death and stroke between the surgicalgroup (10.7%) and the nonsurgical group (11.3%)

In ACAS, between 1987 and 1993, 1662 patients were enrolled from 39centers in North America.66All patients received daily aspirin (325 mg).During operation, patients who were randomly assigned to undergosurgery had a 2.3% risk of stroke and death At 5 years (mean follow-up2.7 years), the risk of ipsilateral stroke was 5.1% for the surgical group,

and 11% for the medical group (P = 004) The overall reduction in

rela-tive risk was 53%, more apparent in men than in women, and independent

TABLE 3 Major trials of CEA in symptom-free patients

Risk of stroke during follow-up (yrs) Carotid

artery

CASANOVA 410 50%-90% CEA vs medical treatment + 10.7 (3) 11.3

aspirin + dipyridamole

ACAS 1662 >60% CEA + aspirin vs aspirin alone 5.1% (5) 11%

of degree of stenosis or of disease in a contralateral artery The benefit ofsurgery was apparent at 10 months and remained significant thereafter.Calculated risk of stroke in the medical group was 2.2% per year.

To summarize, in ACAS and VAAST, two studies in which surgeons andhospitals were selected for their low surgical risk, we have evidence thatCEA can reduce the risk of stroke in selected symptom-free patientswhose stenosis is >50% to 60% VAAST did not include women, and, inACAS, the benefit to women was not apparent; moreover, ACAS enrolled

<5% nonwhite patients The studies also underscore the importance ofcarefully evaluating patients to weigh possible benefit from CEA againsttheir surgical risk and life expectancy

CEA in Patients at High Risk An important subset of patients, those

with carotid artery disease who are at risk not only for stroke but for gical complications from CEA, are as follow:

sur-• Patients with poor cardiopulmonary condition

• Class III or IV congestive heart failure

• Left ventricular ejection fraction (LVEF) < 30%

• Heart surgery within the past 6 weeks

• Recent MI (>24 hours and <4 weeks)

• Unstable angina (Canadian Cardiovascular Society Criteria [CCS]III/IV)

• Forced expiratory volume in 1 second < 0.8

• Patients requiring concomitant CEA and coronary artery bypass grafting (CABG)

• Patients with previous ipsilateral CEA

• Patients with contralateral occluded carotid artery

• Patients with “hostile neck”

• Prior neck dissection

• Prior radiation therapy for head and neck cancers

• Conditions that immobilize the spine (eg, rheumatoid arthritis)

• Patients with surgically inaccessible lesions

• High lesions (greater than C2)

TABLE 4 CEA: Mayo Clinic Risk Classification

• Ostial lesions (below the clavicle)

• Patients with Takayasu’s arteritis

Sundt et al67retrospectively studied 3111 consecutive patients who went CEA, classifying them into 6 classes according to risk on the basis ofneurologic status, comorbid conditions, and angiographic variables (Table4) These authors found that the risk of permanent stroke, MI, or death inpatients who have class VI disease is 8.1%; the mortality rate is 2.9%

under-In a retrospective review of the records of 1160 patients undergoingCEA, McCrory et al68 found a 40% postoperative rate of stroke, death,and MI for those who underwent a concurrent CABG procedure Of thosepatients with angina, the postoperative rate of stroke, death, and MI was9.9% Coyle et al69documented an 18.2% perioperative (30-day) rate ofstroke and death in patients at their institution who underwent a concur-rent CABG Similarly, Goldstein et al70 found an 18.7% postoperativestroke and death rate in symptom-free patients who underwent CEA andconcurrent CABG Patients with congestive heart failure (CHF) experi-enced an 8.6% rate of stroke and death

Vassilidze et al71reported on two separate series of patients at high gical risk who had a concurrent CABG with their CEA The first series ofpatients also had unstable angina and evolving MI: after operation, theyhad a 6% mortality rate and 18% stroke rate The second series ofpatients, who had unstable angina at the time of their procedures, experi-enced a 27.3% rate of postoperative stroke.72Wong et al73also performed

sur-a retrospective chsur-art review sur-and found thsur-at psur-atients with sur-anginsur-a whounderwent CEA had a 12% stroke and mortality rate at 30 days and a 15%rate of heart-related complications (angina, CHF, arrhythmia, MI).Patients with CHF had a 25% stroke and mortality rate and a 50% rate ofheart-related complications

Similarly, patients who have bilateral carotid artery stenosis, a restenoticlesion after CEA, or occluded contralateral carotid arteries are at high riskfor morbidity and death from CEA, as will be discussed later Patientswho have surgically inaccessible lesions or a “hostile neck” are also poorcandidates for CEA and are probably better served by carotid artery stent-ing Another subset of patients who are poor surgical candidates are thosewho have Takayasu’s arteritis Cerebral vascular symptoms in theseyoung patients are common because of a high incidence of majorbranches of the aortic arch being involved in the disease Typically, thesepatients have long areas of stenosis that involve the common carotidartery, resulting in a “string sign” on carotid angiography Carotid arterybypass has been recommended to prevent strokes in such patients; how-

ever, this carries a high risk of death in addition to immediate and latecomplications.

Understandably, these patients are often excluded from CEA trials.Such patients currently have the option of high-risk CEA or medical ther-apy, for which there is a high long-term risk of stroke On the basis of theresults of the above-mentioned trials, the American Heart Associationpublished recommendations for CEA in patients both with and withoutsymptoms (Tables 5 and 6).74,75

Nonsurgical Treatment of Carotid Artery Stenosis

Percutaneous Balloon Angioplasty for Carotid Artery Disease

Percutaneous transluminal balloon angioplasty (PTA) for carotid artery

TABLE 5 AHA Recommendations for CEA for symptom-free patients

Surgical risk is ≤3% and patient’s life expectancy is at least 5 years

Proven

Carotid artery stenosis ≥60% with or without ulceration and with or without antiplatelet apy, regardless of status of contralateral arteries (ranging from disease free to occluded) Acceptable

ther-Unilateral CEA with simultaneous CABG for carotid artery stenosis ≥60% with or without ation and with or without antiplatelet therapy, regardless of status of contralateral arteries (ranging from disease free to occluded)

Acceptable, but not proven

Carotid artery stenosis ≥75% with or without ulceration with contralateral artery stenosis ing from ≥75% to occluded

stenosis was first reported by Kerber et al76in 1980 In 1987 Theron et al77published the results of internal carotid artery angioplasty in 48 patientswith de novo atherosclerosis or postsurgical restenosis The technical suc-cess rate was 94%, with a rate of serious morbidity of 4.1% Kachel’s78review of literature through 1995 reported an overall technical successrate of 96.2% in 523 carotid angioplasty procedures, a 2.1% rate of mor-bidity, a 6.3% rate of transient, minor complications, and no deaths.Gil-Piretta et al79performed 85 balloon angioplasties in 82 patients withsymptoms of stenoses of >70% during a 4-year period Their technicalsuccess rate was 92% (residual stenosis ≤50%), with a 30-day mortalityrate of 0.0% and a 4.9% rate of major morbidity, which compares veryfavorably to rates in ECST and NASCET The rate of recurrent stenosiswas 6.7% at a mean follow-up of 18.7 months, with all cases occurringbetween the third and sixth month This compares favorably with the rate

in reports of CEA series of approximately 10% in the first year The rate

of restenosis reported in other large angioplasty series is 0.0% to 16%.The North American Cerebral Percutaneous Thrombosis Angioplasty Reg-istry80was a prospective, randomized, multicenter cohort study of the angio-graphic efficacy and clinical outcomes of PTA in patients who had symptom-atic carotid artery stenosis ≥70% All were judged to be at high surgical riskfor CEA The Registry reported that of 147 patients (165 PTAs), the averagestenosis before intervention was 84%, reduced by PTA to an average of 37%.Angiographic success, defined as residual stenosis <50%, was achieved in

TABLE 6 AHA Recommendations for CEA for patients with symptoms

Progressive stroke plus ipsilateral carotid artery stenosis ≥70%

CEA ipsilateral to TIA plus carotid artery stenosis ≥70% combined with required CABG

Uncertain

TIA or mild stroke plus carotid artery stenosis 30% to 69%

TIA plus carotid artery stenosis 30% to 69% combined with CABG

Symptomatic acute carotid artery stenosis

Global ischemic syndrome plus carotid artery stenosis ≤30%

Acute dissection with symptoms while receiving heparin

Assuming surgeon’s rate of mortality/morbidity is ≤6%.

83% of all treated lesions Clinical success, defined as residual stenosis <50%and absence of death or recurrent TIAs or stroke in hospital, was achieved in76% of all treated lesions Death from all causes occurred in 3% of patientsand stroke in 6% The combined rate of death and stroke was 9%.

PTA as a stand-alone intervention has been abandoned in the ment of carotid artery stenosis because of its many potential drawbacks,including vessel wall recoil, angiographically documented intimal dissec-tion and plaque dislodgment with particulate embolization, and the highincidence of death and stroke seen in the North American Cerebral Per-cutaneous Thrombosis Angioplasty Registry

manage-Carotid Artery Stenting

The impetus for stent placement has arisen from the findings of trialsthat compare results of stent-assisted balloon angioplasty with those ofballoon angioplasty in the coronary arteries These findings have consis-tently demonstrated a persistent benefit in event-free survival at 1 yearand a lower rate of repeat angioplasty The advantages of stent placementover simple angioplasty include avoiding intimal dissection, any elasticrecoil, and the problem of late restenosis

The viability of carotid artery PTA and stenting depends on the ity of the stent, and this requires long-term structural stability of the stentdevice Balloon-expandable stents, which can be predictably expanded tothe maximal vessel diameter, have been shown to be unsuitable for carotidbifurcation where external forces can produce in vivo deformation Stentcollapse was observed in a significant number of Palmaz stents (Johnsonand Johnson Interventional Systems Co, Warren, NJ) within 6 months ofplacement in the carotid arteries.81 The likely explanation for this phe-nomenon is the effect of external compression, although no instances ofneck trauma were noted in those patients Movement of the neck thatexerts stretching, twisting, and kinking forces on the blood vessels isanother possible mechanism Self-expanding stents (such as the Wallstent[Boston Scientific Corp, Quincy, Mass] and SMART stent [CordisEndovascular, Warren, NJ]) that continue to exert outward radial force arethe most commonly used for carotid artery stenosis at the present time.Worldwide, many different centers have reported on nonrandomizedseries of patients who have undergone carotid artery stenting Most ofthese studies involved patients who were at a high surgical risk for CEAand would not have met the inclusion criteria of NASCET and ESCT.Diethrich et al82in 1996 reported their data on 117 carotid artery stents

durabil-in 110 patients (31 with and 79 without symptoms) Of these, 109 patients(99%) (116 arteries, 99.1%) were successfully treated with 129 stents

One (0.9%) percutaneous procedure failed because of technical reasons.There were 7 strokes (2 major and 5 reversible; 6.4%) and 5 minor tran-sient events (4.5%) that resolved in 24 hours Three patients were con-verted to CEA before discharge; one patient who had had a stroke died(0.9%) In the 30-day postprocedural period, 2 ICA stents becameoccluded (these patients were symptom free) The clinical success rate at

30 days was 89.1% (98/110) At 7.6 months follow-up, no new neurologicsymptoms developed Routine duplex scanning in symptom-free patientsrevealed one stent occlusion at 2 months and one case of flow-limitingintimal hyperplasia at 7 months Life-table analysis shows an 89% cumu-lative rate of primary patency

In 107 patients who underwent elective carotid artery stent placement,Yadav et al83 reported that 77% were at high risk who did not meetNASCET inclusion criteria, suggesting that, had they been enrolled inNASCET, their rate of surgical complications would have been higher.There were 7 minor strokes, 2 major strokes, and 1 death during the first

30 days There were no strokes during the follow-up period At 6 months,angiography revealed that 4.9% of patients had asymptomatic restenosis

In their study of outcomes in a high-risk group of 199 patients, Henry et

al84reported a low incidence of stroke and death (1.5%) that matched that

of minor stroke (1.5%)

Malek et al85reported on 28 symptomatic NASCET ineligible patientswho underwent carotid PTA and stenting Their technical success rate was100% There were no periprocedural deaths, only one major stroke(3.6%), no minor strokes, and 3 TIAs (10.7%) In-hospital complicationsincluded 2 fatal MIs No surviving patients had further strokes

Shawl et al86evaluated the safety and efficacy of elective carotid arterystenting in 170 consecutive patients at high risk (192 carotid arteries).This series represents a very high–risk group that included patients whohad unstable angina, previous ipsilateral CEA, contralateral carotid arteryocclusion, and other severe comorbid illnesses Their technical successrate was 99%, including 73 patients who underwent coronary artery inter-vention The total 30-day stroke rate was 2.9% for treated patients or 2.6%for treated arteries (1 major and 4 minor) There was no death or MIwithin 30 days of stenting At a mean follow-up of 19 ± 11 months, 3patients (2%) had asymptomatic restenosis, and there was no major stroke

or neurologic-related death

We87 have reported our 3-year experience of treating 100 elderlypatients (>65 years) whose conditions were considered inoperable Ofthese patients, 85% had symptoms (TIA in 60 and stroke in 25) Morethan three quarters (n = 80) of our patients had concomitant CAD that was

severe in 30 (>70% stenosis in 2 or more epicardial coronary arteries),and 25 had severe left ventricular dysfunction (EF ≤ 20%) The procedurewas technically successful in all patients, with only one major stroke and

no deaths After the procedure, the rate of minor complications was 15%,which included reversible neurologic deficit (5%), pulmonary edema(3%), prolonged hypotension (3%), vascular access complications (3%),and neck hematoma (1%) A restenosis rate of 1% (>50% stenosis) wasnoted at a mean 12.1 ± 9.2 months follow-up The overall rate of neuro-logic complications in this population was 6%, most of which were tran-sient neurologic deficits that resolved completely within 24 hours.When Mathur et al88retrospectively analyzed risk factors for stroke in

231 patients who were undergoing elective carotid artery stenting, theyfound that 14% were NASCET eligible Overall, their rate of stroke at 30days was 6.9%; however, when reclassified by NASCET eligibility crite-ria, this group’s rate of stroke was only 2.7% Independent predictors ofperiprocedural strokes were advanced age (>80 years) or multiplestenoses However, there was no increased risk of an adverse outcome inpatients who underwent stent placement for contralateral carotid arteryocclusion, stenting after a previous CEA, or stenting as a combinedcarotid and coronary artery procedure Treated by CEA, all of these fac-tors are associated with a higher incidence of complications

Vitek et al89 treated 404 patients with carotid artery angioplasty andstent placement Their technical success rate was 98%, the 30-day mor-tality and morbidity rate was 1.9%, the rate of major stroke was 0.7%; theminor stroke rate was 5.8%, and there was a 5% rate of restenosis (>50%narrowing), 65% of which was due to collapse of a balloon-expandablestent These investigators reported a lower complication rate in the last

122 patients (with increased procedure-related experience): their minorstroke rate was 2.5%, with no major strokes or death

Roubin et al90 monitored 528 consecutive patients (604 arteries) whounderwent carotid artery stenting At 30 days, the rate of fatal stroke was0.6% and 1% for non-stroke-related death The rate of major stroke was1%, and the rate for minor stroke was 4.8% The overall 30-day stroke andmortality rate was 7.4% Over the 5-year study period, the 30-day minorstroke rate improved from 7.1% for the first year to 3.1% for the fifth year

(P < 05) The best predictor of 30-day stroke and death was age ≥80years After the 30-day period, the incidence of fatal and nonfatal strokewas 3.2% Three-year freedom from ipsilateral fatal stroke was 92% ±1% Late follow-up also demonstrated a low rate of fatal and nonfatalstroke

Wholey et al91conducted a survey of 36 major carotid artery

interven-tional centers in Europe, Asia, and South and North America and lished the global experience in cervical carotid artery stent placement.They reported that 4749 patients (5210 diseased carotid arteries) under-went carotid artery stent procedures A technical success rate of 98.4%was reported, with nearly all (5126) arteries successfully stented Dur-ing the 30-day follow-up period, there were 134 TIAs, for a rate of 2.57%

pub-on the basis of the total number of vessels treated and 2.82% pub-on the basis

of the total number of patients enrolled

There were 129 minor strokes with a rate of occurrence of 2.48% on thebasis of vessels treated and 2.72% on the basis of patient numbers Therewere 71 major strokes, for a rate of 1.36% on the basis of vessels treatedand 1.49% on the basis of the patient volume The range of major strokewas 0.0% to 7.7%; the average rate of major strokes was 2.02% per cen-ter Within a 30-day period, there were 41 procedure-related deaths, with

a mortality rate of 0.79% on the basis of vessels treated and 0.86% on thebasis of patient volume There was a 4.63% rate for combined minor andmajor stroke and procedure-related death on the basis of vessel treatedand 5.07% on the basis of patient volume The combined rate of minorand major stroke and procedure-related death rate was 5.76% involvingpatients with and 3.38% involving patients without symptoms

Follow-up ultrasound studies were performed at 1, 6, and 12 monthsafter stent placement At 6 months 96% (4502) of the patients were mon-itored, and at 12 months 84% (3924) were followed up The restenosisrate was approximately 2.27% At 12 months, the rate was 3.36% Duringthe 6- to 12-month follow-up period, there were 56 new neurologic events(TIAs and strokes) and neurologic-related deaths reported for a rate of1.39% This was determined with 3924 (84%) patients for follow-up.Golledge et al92systematically compared the early outcome of PTA andCEA for symptomatic carotid artery disease Thirty-three studies (13angioplasty and 20 CEA) were included in this analysis Carotid arterystents were deployed in 44% of patients undergoing angioplasty Themortality rate within 30 days of PTA was 0.8% compared with 1.2% after

CEA (P = 6) The stroke rate was 7.1% for PTA and 3.3% for tomy (P < 001), whereas the risk of fatal or disabling stroke was 3.2% and 1.6%, respectively (P < 01) The risk of stroke or death was 7.8% for angioplasty and 4% for endarterectomy (P < 001), whereas that of fatal

endarterec-or disabling stroke was 3.9% after PTA and 2.2% after CEA (P < 01).

Technical success rate with angioplasty was 93%

Jordan et al93 retrospectively compared 107 patients who underwentCEA with 166 patients who had carotid artery stenting and monitoredthem prospectively The stent group had a higher rate of early minor

stroke (6.6% vs 0.6%), but the CEA group had a higher rate of majorstroke and death (4.2% vs 2.8%).

The Carotid and Vertebral Artery Transluminal Angioplasty Study(CAVATAS)94 compared carotid angioplasty (with bailout stenting in26%) and CEA It reported equivalent combined stroke and mortalityrates for angioplasty and CEA (10% and 9.9%, respectively) at 30 days

Of the 96% of patients who had symptoms, a large number wereNASCET ineligible The 3-year freedom from ipsilateral stroke and deathwas similar between the angioplasty and the CEA groups

The above-mentioned reports have clearly shown that, in a group ofpatients who are either at high surgical risk for CEA or not eligible for theprocedure, carotid artery stenting can be performed with excellent angio-graphic results and low procedure-related risks of complications and latestenosis (Table 7) Large-scale multicenter randomized trials are currentlyunderway to validate the results of these nonrandomized cohort studies.Data from the Schneider WALLSTENT trial was recently made avail-able at the American Stroke Association’s 26th International Stroke Con-ference The trial enrolled 223 patients who have had a stroke or TIA andangiographically documented carotid artery stenosis of 60% to 99% withlesions treatable by either PTA/stenting or CEA Of these 223 patients,

108 were treated with stents and 115 by CEA Follow-up data were able for only 113 patients

avail-Primary end points (ipsilateral stroke, any periprocedural death, and anyvascular death at 1 year after treatment) were significantly higher in thestent group than in the CEA group at 2 days (6.5% stent vs 0.9% in CEA),and at 1 year (12% stent vs 3.5% CEA) The difference was evident at 30days (10.2% stent vs 3.5% CEA) but not significant Although the techni-cal success rate was 97% (defined as <30% residual stenosis), the trial

TABLE 7 Results of carotid artery stenting

Early (30 day) outcomes Number

patients/ success stroke stroke Death strokes rate

was prematurely stopped by the company Experience significantlyeffected complication rates, which were higher in low-volume centers.This study has raised many issues, including the implications of com-paring a procedure very early in its development to one that is firmlyestablished To be eligible for the WALLSTENT study, surgeons had tohave a complication rate of ≤6% On the other hand, stent operators had

to have a complication rate of 1% in 10 completed procedures or, if theywere new to the procedure, to be proctored for 10 procedures

Simultaneous Carotid and Coronary Artery Interventions

Historically ≥50% of the patients undergoing CEA have significantCAD.95In such patients, CEA has been associated with combined majorevent (stroke, MI, and death) rates of 8.8% to 10% Likewise, CABG inthe presence of carotid artery disease has been associated with a 4% to20% risk of perioperative stroke.96-99

In a metaanalysis100 of 16 studies, 899 patients underwent combinedCEA and CABG, and another 920 underwent staged procedures Thecrude event rates for stroke were 6.0% for the combined procedure groupand 3.2% for the staged procedure group; mortality rates were 4.7% ver-sus 2.9%, respectively Combined rates of death or stroke were 9.5% ver-sus 5.7%, respectively Although simultaneous CEA and CABG havebeen advocated as a safe surgical alternative, recent reports have shownthat this approach resulted in a combined perioperative stroke and deathrate of 8% to 18%

Al Mubarak et al101 reported on 51 patients who underwent carotidartery stenting with simultaneous or staged percutaneous coronary arteryinterventions for severe coexisting CAD All patients had symptomaticCAD, 65% had recent symptoms (<3 months) related to carotid arterystenosis In all, 17 patients underwent simultaneous carotid artery stent-ing and coronary angioplasty, with the coronary artery approached first in

12 (71%) The remaining 34 patients had staged intervention with nary artery angioplasty performed first in 22 patients (65%) The meaninterval between the procedures was 26 ± 7 days (range 2 to 36 days).PTCA was performed in 71 coronary arteries, of which 52 (73%) werestented A total of 54 carotid arteries were stented Bilateral carotid arterystenting was performed simultaneously in 1 patient and staged in 2 oth-ers The technical success rate was 100% in carotid arteries and 98.5% incoronary arteries Only 2 patients who had simultaneous procedures had

coro-a minor stroke, ecoro-ach with worsening of the Ncoro-ationcoro-al Institute of Hecoro-althStroke Scale (NIHSS) by 1 to 2 points They recovered completely within

3 days There were no other major neurologic events or death or MI in the

30-day follow-up period; all patients remained symptom free There were

no neurologic events, coronary events, or death, and no repeat procedureswere required This study demonstrates the safety and effectiveness ofstaged or simultaneous carotid artery stenting and coronary angioplasty intreating patients who have severe occlusive disease in both vascular terri-tories

Carotid Artery Stenosis With Contralateral Occlusion

Patients who have bilateral carotid artery disease with one occludedartery have a poor prognosis with medical therapy alone.102,103Increasedlong-term risk for stroke in such medically treated patients is related tothe inadequacy of collateral circulation, both from the circle of Willisand from the leptomeningeal vessels In patients who have contralateralocclusion, although CEA does reduce the risk of ipsilateral stroke, theprocedure increases the incidence of perioperative neurologic complica-tions compared with those who have a patent contralateral carotidartery.104-107In a patient who has contralateral occlusion, cerebral bloodflow is reduced during cross-clamping of the common carotid artery,possibly creating an area of microinfarctions, the clinical effect of whichmay not be apparent on gross neurologic examination, only on cognitivetesting

When Mathur et al108reported on their series of 26 patients treated withcarotid artery stenting in the presence of contralateral carotid artery occlu-sion, their procedural success rate was 96% The mean diameter of steno-sis was reduced from 76% ± 15% to 2.8% ± 5% There was one (3.8%)minor stroke in a patient in whom an air embolism developed during base-line angiography At mean follow-up of 16 ± 9.5 months, there was noneurologic event in any patient

Mericle et al,109reporting on elective stent placement in 23 patients withhigh-grade carotid artery stenosis and contralateral carotid artery occlu-sion, cited a 0.0% rate for 30-day perioperative stroke and death In con-trast, the perioperative stroke and death rate in similar patients inNASCET was 14.3% (Figs 3 and 4)

Carotid Artery Stenosis with Prior Radiation Exposure

Radiation-induced carotid artery stenosis is more difficult to treat cally because of long lesions, and there is periarterial scarring, ill-definedplanes of resection, and a high rate of wound complications In their 910-patient study of patients who had prior radiation exposure, Elerding et

surgi-al110found a 6.3% incidence of stroke at a mean of 9 years The logic condition is believed to be accelerated atherosclerosis in which

patho-panarteritis can involve irradiated regions anywhere from the origin of thecarotid artery to the cranial base.

In 14 patients (15 arteries) who had radiation-induced carotid arteryocclusive disease that was treated by PTA and stenting, Al-Mubarak et

al111 reported a technical success rate of 100% and a reduction in meanstenosis from 77% ± 6% to 8% ± 2% In 2 patients, ipsilateral vertebral

FIG 3 Man 58 years old who had history of CEA on right side was diagnosed with symptoms tive of TIAs Carotid artery duplex ultrasonography revealed high-grade stenosis in right ICA and

sugges-occluded left ICA Angiography shows (A) high-grade stenosis in right ICA (arrow) and visible clips from

prior CEA.

A

arteries were stented concomitantly One patient had a minor stroke afterthe procedure but recovered fully in 2 days In the 9 patients (64%) whounderwent 6-month follow-up imaging, there was no evidence of resteno-sis (obstruction ≥50%) At 18 ± 2 months, 3 (21%) patients died of unre-lated causes There were no neurologic events or need for repeat carotidartery interventions Carotid artery stenting is an effective treatmentoption for patients who have severe radiation-induced carotid artery dis-ease (Fig 5).

Carotid Artery Stenting in Restenotic Lesions after

Endarterectomy

Reports indicate that up to 28% of patients have restenosis after CEA,although more recently the average rate has been 13%.112-115The risk ofsubsequent stroke in these patients is 8% to 17%, depending on the inter-val from when CEA is performed.112-116Accompanying neurologic eventshave been reported in only 1% to 5% of these patients Early restenosis(within the first 24 months) is due to myointimal hyperplasia; delayed

FIG 3 (continued) (B) Blood flow to left cerebral hemisphere through right carotid artery via circle of Willis indicates occluded left carotid artery.

B