Carotid Artery Stenting: : State of the Art

Carotid Artery Stenting: State of the Art

KASJA RABE, CAND. MED., and HORST SIEVERT, M.D.

From the CardioVascular Center Frankfurt, Sankt Katharinen, Frankfurt, Germany

Carotid artery stenting (CAS) is growing as an alternative to carotid artery endarterectomy. Nowadays, it isperformed routinely in many centers worldwide. Still, it is discussed controversially although several clinical trialshave shown equivalency or superiority of catheter treatment at least in high-risk patients. What is still missing isa randomized trial in non-high-risk patients. This is an overview about the completed and ongoing trials as wellas the current stent and embolic protection technology. (J Interven Cardiol 2004;17:417–426)

Introduction

Although carotid artery stenting (CAS) has alreadybeen performed for 25 years, there is no general agree-ment whether it should be accepted as an alternativemethod to carotid endarterectomy (CEA). This contro-versy is caused by the lack of large randomized trialscomparing endarterectomy to stenting particularly innon-high-risk patients.

The benefit of endarterectomy in patients with cere-brovascular disease has been shown in the early 1990s,when—after more than 1 million carotid surgeries wereperformed worldwide—several randomized trials wereperformed comparing endarterectomy to medical treat-ment. This year, the latest trial (ACST)1 has been pub-lished, which proved the positive effect of endarterec-tomy in asymptomatic patients in reducing stroke anddeath within 5 years.

After having performed angioplasty in coronaryand peripheral vascular disease with excellent results,carotid angioplasty was thought to be an opportunityto simplify the treatment of a carotid stenosis, as it the-oretically had many advantages compared to carotidendarterectomy. As the common patient with carotidstenosis is of higher age and has several comorbidities,anesthesia runs a potential risk of perioperative compli-cations, which can be avoided by CAS. Local wound

Address for reprints: Prof. Dr. Horst Sievert, Cardiovascular CenterFrankfurt, Sankt Katharinen, Seckbacher Landstrasse 65, 60389Frankfurt, Germany. Fax: +49-69-4603-1343.

problems or cranial nerve palsies do not occur afterstenting. Usually, the patient can be dismissed within24 hours, which reduces costs.

CAS has made a huge development. The first an-gioplasty was performed in 1979 by Mathias.2 Thefirst stent was deployed in 1989,2 and the first cerebralprotection device was described in 1990 by Theron.3

The invention and improvement of the devices, to-gether with the experience of the operators, led to lowercomplication rates shown in several trials and clinicalseries.

Results of Carotid Endarterectomy

After the North American Symptomatic Carotid En-darterectomy Trial4 (NASCET) published in 1991,carotid endarterectomy was considered to be the goldstandard for the treatment of carotid stenosis. There-fore, the results of carotid stenting have to be comparedwith the results of NASCET and other randomizedtrials (ECST,5 ACAS,6 CASANOVA,7 and the VA8

trial). The stroke and death rate at 30 days in thesetrials ranged from 5.8% to 7.5% in the symptomaticpatients and from 2.3% to 4.3% in the asymptomaticpatients.

North American Symptomatic Carotid Endar-terectomy Trial (NASCET). 4 The NASCET trial wasinitiated in 1988 and published in 1991. It was a ran-domized, multicenter, controlled trial of 659 patientsin 106 centres. The purpose was to show the benefitof carotid endarterectomy in patients with moderate

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or severe stenoses. Patients with symptomatic internalcarotid artery stenoses of more than 70% were ran-domized to receive either endarterectomy or medicaltreatment. Assessment was made at 1, 3, 6, 9, and 12months and every 4 months thereafter.

Of the surgical patients, 5.8% experienced a strokeor death within 30 days. About 7.6% of patients treatedwith endarterectomy suffered from cranial nerve palsyand 5.5% from neck hematoma.

The cumulative risk of ipsilateral stroke at 2 yearswas 9% for the surgical group and 26% for the medicalgroup. This is an absolute risk reduction of 17%. Therisk of major or fatal stroke at 2 years was 2.5% forCEA and 13.1% for medical therapy.

The risk of ipsilateral stroke was also significantlyreduced (P = 0.045) in patients with a carotid steno-sis of 50–69% who received carotid endarterectomy.Patients with stenoses of 70–99% showed the most sig-nificant reduction (P < 0.001) in the rate of ipsilateralstroke while patients with stenosis < 50% did not showa significantly lower rate of ipsilateral stroke.

European Carotid Surgery Trial (ECST).5 TheEuropean Carotid Surgery Trial (ECST) was a mul-ticenter, randomized, controlled trial of 778 patientsfrom 97 centers. Results were published in 1998. Thepurpose of this trial was to assess the risks and bene-fits of carotid endarterectomy in patients with a recentnondisabling stroke, a transient ischemic attack, or aretinal infarct probably due to a carotid stenosis.

The risk of major stroke or death was not reduced sig-nificantly. There was no benefit from CEA in patientswith mild <30% stenosis, but there was an absolute11.6% benefit from surgery after 3 years in patientswith stenosis > 80% in diameter. Surgical patients hada perioperative stroke and death rate of 7.1% overall.The 3-year risk of any death or stroke was 12.3% in thesurgical group and 21.9% in patients treated with med-ication alone. Variations in risk with age and sex werefound to modify the results. In 6.4% of the patientstreated surgically, cranial nerve palsy was observed.

Asymptomatic Carotid Atherosclerosis Study(ACAS).6 The results of the Asymptomatic CarotidAtherosclerosis Study (ACAS) were published in 1995.The aim of the study was to determine whether theaddition of carotid endarterectomy to medical treat-ment could reduce the incidence of cerebral infarctionin patients with asymptomatic carotid artery stenosisof more than 60%. The ACAS was a prospective, ran-domized, multicenter trial. The risk of perioperativestroke at 30 days was 2.3% in the surgical group. The

risk of ipsilateral stroke and any perioperative strokeor death was estimated to be 5.1% for surgical patientsand 11.0% for patients treated medically at 2 years.

Despite the ACAS findings, some investigators stillfeel that an insufficient evidence exists to recommendsurgery in asymptomatic patients. It is estimated that83 carotid endarterectomies must be performed to pre-vent one stroke or death over a 2-year period amongasymptomatic patients.

Its clinical importance is controversial. The compli-cation rate (stroke or death) reported in ACAS is lowerthan generally achievable even in centers with consid-erable surgical experience.

Carotid Artery Surgery Asymptomatic Narrow-ing Operation Versus Aspirin (CASANOVA).7 TheCarotid Artery Surgery Asymptomatic NarrowingOperation Versus Aspirin (CASANOVA) trial random-ized 410 asymptomatic patients to surgical and medicaltreatment or to medical management alone. After 30days, 3.6% of the surgical patients suffered from deathor stroke. The result of the trial showed no significantdifference between both groups. However, nearly halfof the patients in the “no immediate surgery” groupeventually did have an endarterectomy for one of thefollowing reasons: after developing ischemic symp-toms, progressive severe stenosis, bilateral stenosis,or contralateral stenosis. This study’s unusual designlessens its statistical validity.

Veterans Affairs Asymptomatic CarotidEndarterectomy Trial.8 In the Veterans Af-fairs Asymptomatic Carotid Endarterectomy Trial(VA trial), 444 asymptomatic patients were included.They were treated either medically or surgically. Therisk of stroke and death was not significantly differentin both groups. In the surgical group, 4.3% of thepatients suffered from death or stroke within 30 days.After a mean follow-up of 47.9 months, the combinedincidence of ipsilateral neurological events was 8.0%in the surgical group and 20.6% in the medical group.

Carotid Endarterectomy and Prevention of Cere-bral Ischemia in Symptomatic Carotid StenosisTrial.9 The symptomatic trial of the Veterans AffairsTrialist Group included 189 patients. The inclusion wasstopped prematurely because of the results of two sim-ilar trials (NASCET and ECST), which demonstratedan overwhelming benefit from carotid endarterectomyfor symptomatic patients with high-grade stenosis. Thestroke and death rate after 30 days was 5.8% in thesurgical group in this VA trial. At a mean follow-up of11.9 months, there was a significant reduction in stroke

418 Journal of Interventional Cardiology Vol. 17, No. 6, 2004

RESULTS OF CAS

or crescendo transient ischemic attacks in patients whoreceived surgery (7.7%) compared with nonsurgical pa-tients (19.4%).

Asymptomatic Carotid Surgery Trial (ACST).1

During 1993–2003, 3,120 asymptomatic patients withcarotid stenosis were randomized between immedi-ate or deferred endarterectomy. The risk of stroke anddeath within 30 days was 3.1% for endarterectomy.Within 5 years, the stroke rate was 6.4% (CEA) versus11.8% (medical treatment, surgery only if patient be-comes symptomatic). This trial showed a benefit fromsurgery for asymptomatic patients younger than 75years with a carotid stenosis of at least 70% diagnosedby ultrasound.

The results of the NASCET trial request skills of thesurgeons to allow a perioperative stroke and death rateof 6% for symptomatic and, according to the ACAStrial, a rate of 3% for asymptomatic patients to have abenefit from endarterectomy.

Patients should also be carefully selected. In theNASCET trial only one-third (Table 1) of patients andin the ACAS trial every 25th patient was included. Theonly high-risk group within the NASCET trial werepatients with a contralateral occlusion. Those patientshad a combined stroke and death rate of 14%.10 Othernonrandomized trials reported on the results of CEA inhigh-risk patients, e.g., patients with previous CEA, se-vere CAD, and high comorbidity. They found a strokeand death rate from 7.4% to 12%.

It is assumed that the perioperative risk of en-darterectomy is higher in hospitals with lower skilledsurgeons, e.g., as reported by Chaturvedi et al. in amulticenter study11 and by Wennberg et al. in a meta-analysis.12

Table 1. Exclusion Criteria of the NASCET Trial

Organ failure of heart, kidney, liver, or lungRecent MIUnstable anginaPrevious endarterectomy with recurrent stenosisAge > 79 yearsCancer judged likely to cause death within 5 yearsIntracranial lesion more severe than the treated stenosisCardiac valvular or rhythm disorderUncontrolled hypertensionUncontrolled diabetes mellitusContralateral endarterectomy within

the previous 4 months

Results of CAS

Early clinical series of carotid stenting have led tothe assumption that carotid stenting is a promising al-ternative to endarterectomy due to a low morbidityand mortality rate. Since then, only a few random-ized trials comparing carotid stenting to CEA havebeen published. The CAVATAS trial13 was the first togive comparable results for carotid stenting and CEA.Brooks published a small trial that took place in acommunity hospital.14 He also found comparable re-sults of surgery and stenting. The latest trial comparingCEA to stenting with an embolic protection device isSAPPHIRE.15

Several other trials have been published or areunder way: ARCHER,16 SECURITY,17 MAVERIC,7

SPACE,7 ICSS = CAVATAS II,7 CARESS,7 CREST,7

BEACH (Boston Scientific EPI: A Carotid Stent-ing Trial for High Risk Surgical Patients),7 EVA 3S(Endarterectomy Versus Angioplasty in patients withSevere Symptomatic Carotid Stenosis),7 CABER-NET (Carotid Artery Revascularization Using theBoston Scientific EPI FilterWire ExTM and theEndoTexTM NexStentTM),7 SHELTER (Stenting ofHigh risk patients Extracranial Lesions Trial withEmboli Removal),7 and MOMA (Multicenter Reg-istry to Assess the Safety and Efficacy of theMO.MA Cerebral Protection Device during CarotidStenting).18

In the world registry published by Wholey,19 andthe observational studies performed by Roubin,20 Cre-monesi,21 and others a stroke and death rate from 1%to 7% has been reported.

Clinical Series of Carotid Stenting

Updated Review of the Global Carotid ArteryStent Registry.19 Wholey et al. established a world-wide registry including 12,392 procedures in 53 cen-ters. The technical success rate was 98.9% and the com-bined death or stroke rate was 4.75%.

Immediate and Late Clinical Outcomes of CASin Patients with Symptomatic and AsymptomaticCarotid Artery Stenosis: A 5-Year ProspectiveAnalysis.20 In 2001, Roubin et al. reported about aseries of 528 consecutive patients undergoing carotidstenting. The major stroke rate was 1% (n = 6), andthe minor stroke rate was 4.8% (n = 29). The overall30-day stroke and death rate was 7.4%.


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Protected Carotid Stenting: Clinical Advantagesand Complications of Embolic Protection Devicesin 442 Consecutive Patients.21 In 2003, Cremonesiet al. published a series of 513 consecutive patientstreated with CAS under embolic protection. Only 1.1%of the patients experienced either a stroke or deathwithin 30 days.

Routine Use of Cerebral Protection During CAS:Results of a Multicenter Registry of 753 Patients.22

Reimers et al. published in 2004 a series of 808 success-ful stent procedures in 753 patients. The rate of strokeand death within 30 days of the procedure was 3.8%for symptomatic lesions and 3.2% for asymptomaticlesions

Clinical Trials

AcculinkTM for Revascularization of Carotidsin High-Risk Patients (ARCHER).16 The ARCHERtrial was a multicenter single-armed trial evaluatingCAS in patients at high risk for CEA. In 41 centres,513 patients with a symptomatic stenosis exceeding50% or an 80% asymptomatic stenosis and matchingat least one high-risk criterion were included. Meanage was 69 ± 10 years, 67% were male, and 63%had a history of stroke, TIA, or amaurosis fugax. Thestroke and death rate at 30 days was 6.6%, and stroke,death, or myocardial infarction occurred in 7.8% of thepatients.

Registry Study to Evaluate the Neuroshield BareWire Cerebral Protection System and X-Act Stentin Patients at High Risk for Carotid Endarterec-tomy (SECURITY).17 The Security trial included305 patients in whom the X-act stent and the neu-roshield embolic protection device were used. Meanage was 74 ± 9 years, whereas 86 patients were olderthan 80. The combined stroke, death, and myocar-dial infarction rate was 7.2% and the stroke and deathrate was 6.9%. About 66% of the filters containeddebris.

Multicenter Registry to Assess the Safety andEfficacy of the MO.MA Cerebral ProtectionDevice During Carotid Stenting.22 The MO.MA trialenrolled 157 patients. The procedure was technicallyand angiographically successful in all procedures. In79.6%, there was macroscopic evidence of debris afterfiltering the aspirated blood. The death and stroke rateat discharge was 2.55%. Within 30 days, the death andstroke rate was 5.73%.

Randomized Trials

Carotid and Vertebral Transluminal AngioplastyStudy (CAVATAS).13 The Carotid and VertebralTransluminal Angioplasty Study (CAVATAS) was arandomized trial with 504 patients from 24 centres in-cluding symptomatic and asymptomatic patients be-ing eligible for both CEA and angioplasty. As the in-clusion criteria were less restrictive, the patients re-sembled more the common population with carotidstenosis. The risk of major stroke or death within30 days of treatment was 6.4% for the endovasculargroup and 5.9% for the surgical group. It was 10%for patients who had undergone angioplasty and 9.9%for patients who had undergone CEA considering anystroke lasting more than 7 days or death. Confirmingthe incidence of other complications observed in theNASCET trial, CEA was associated in 8.7% with a cra-nial nerve palsy rate and in 6.7% with local hematomas(Table 2).

The “stopped trial. .”23 The randomized studyof carotid angioplasty and stenting versus carotidendarterectomy: A “stopped trial” published byNaylor was conducted as a prospective consecutiverandomized trial in a university teaching hospitalincluding symptomatic patients with at least 70%stenosis. Only 17 patients were included because 5 of7 patients treated with angioplasty and none of the sur-gically treated patients experienced a stroke, which ledto a stop of the trial initiated by the Data MonitoringCommittee.

Carotid Angioplasty and Stenting Versus CarotidEndarterectomy: Randomized Trial in a Commu-nity Hospital.14 Brooks at al. performed a small ran-domized trial in a community hospital. One hundredand four symptomatic patients with 70% exceedingstenosis were included. One death occurred in the CEAgroup (2%) and one TIA in the CAS group (1.9). Thelength of stay in hospital was similar, although the CASgroup tended to be discharged earlier (1.8 days vs. 2.7days).

Table 2. CAVATAS Trial: 30-Day Results

Angioplasty (%) Surgery (%) P

Major stroke and death 6.4 5.9 NSStroke or death 10 10 NSCranial nerve palsy 0 9 <0.0001Hematoma 1 7 <0.0015


RESULTS OF CAS

Stenting and Angioplasty with Protectionin Patients at High Risk for Endarterectomy(SAPPHIRE).15 The SAPPHIRE trial is the firstrandomized trial revealing significant superior resultsin the CAS arm. A recruitment of 600–900 patientswas planned. But until being stopped due to lowenrollment it had included 307 patients of 29 centerswith an asymptomatic stenosis exceeding 50% or asymptomatic stenosis exceeding 80% and at least onecomorbidity criteria (Table 3). A team consisting of avascular surgeon, a neurologist, and an intervention-alist determined if the patient was eligible for eitherCAS or CEA. Excluded patients were entered in aregistry and not randomized. Four hundred and ninepatients refused to be randomized or were consideredtoo high risk for surgery and entered the stent registry.Seven patients entered the surgical registry. All CASpatients received a cordis nitinol carotid stent. Theembolic protection device used was the AngioGuardfilter.

Primary endpoint was combined death, stroke, ormyocardial infarction at 30 days. There was a signifi-cant difference in the two groups. It was 5.8% for CASpatients and 12.6% for patients treated with CEA. Thecombined death and stroke rate at 30 days was 4.5%for the CAS group and 6.6% for the CEA group.

Ongoing Trials

Evaluation of the Medtronic AVE Self-ExpandingCarotid Stent System with Distal Protection in theTreatment of Carotid Stenosis (MAVERIC).7 Thistrial begins with a Phase I feasibility study, enrollingpatients at 10 clinical sites across the United States.Currently, 99 patients are included with a stroke rate of

Table 3. Inclusion Criteria of the SAPPHIRE Trial

Congestive heart failureLVEF < 30Open heart surgery within 6 weeksRecent MIUnstable anginaSevere pulmonary diseaseContralateral occlusionRadiation therapy to neckContralateral laryngeal nerve palsyPrevious endarterectomy with recurrent stenosisHigh cervical ICA lesion of CCA lesion below the clavicleSevere tandem stenosisAge > 80 years

4% and a death rate of 2%. Upon completion of Phase I,the trial will proceed to a Phase II registry, scheduled toenroll 350 patients at 40 U.S. clinical sites. The resultsare planned to be published next year.

Stent-Protected Percutaneous Angioplasty of theCarotid Versus Endarterectomy (SPACE).7 TheSPACE trial is a prospective, randomized, indepen-dently controlled, multicenter trial taking place in Ger-many, Austria, and Switzerland. Starting in March2001 until now more than 500 patients have been en-rolled. The study plans to enroll 1,900 patients. Symp-tomatic patients with a high-graded stenosis can berecruited. Embolic protection is optional. Three coor-dinators (vascular surgery, neuroradiology, neurology)supervise this multidisciplinary trial.

International Carotid Stenting Study(ICSS/Cavatas-II).7 The ICSS Study is an open,prospective, randomized, multicenter trial includingsymptomatic patients with a severe (>70%) stenosis.Recruitment began in 2001 and it is expected tocontinue for 5 years, with a planned enrollment of2,000 patients. In March 2003, 107 patients have beenrandomized at 18 centres.

Carotid Revascularization Endarterectomy Ver-sus Stent Trial (CREST).7 The CREST trial includessymptomatic patients of a NASCET like populationwith a stenosis exceeding 50%. To ensure the higheststandards for the trial, both surgeons and stent oper-ators are undergoing rigorous credentialing prior torandomization. A total of 1,377 carotid stent caseswere enrolled so far with an overall stroke and deathrate of 4.8%. Follow-up will last for 4 years, includ-ing clinic visits at 1, 6, 12, 18, 24, 30, 36, 42, and48 months.

Carotid Revascularization with Endarterectomyor Stenting Systems (CARESS).7 In the CARESSstudy, symptomatic and asymptomatic patients are in-cluded which are not eligible for the CREST study. Itevaluates CAS versus CEA in a prospective trial re-cruiting all consecutive eligible patients. Four hundredand fifty patients are planned to recruit in the feasibilityphase and 3,000 patients in the pivotal phase.

Stents and Cerebral Protection Devices

As CAS is a relatively new procedure and an inter-esting alternative to endarterectomy for patients andphysicians, devices are improving constantly. We givea short description of current stents and cerebral pro-tection devices (Tables 4 and 5).


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Table 4. Carotid Stents

Length LengthMin Max Min Max Mono-Rail Tapered Version

Carotid Wallstent (Boston Scientific) 30 50 6 10 yes noExponent (Medtronic) 20 40 6 10 yes noXact (Abbott) 20 30 7 10 yes yesAcculink (Guidant) 20 40 5 10 yes yesSinus-Carotid (OptiMed) 20 40 5 9 no yesNexStent (Endotex) 30 30 4–9 4–9 no yesConformexx (Bard) 20 40 6 12 no noPrecise (Cordis) 20 40 5 10 no noZilver (Cook) 20 60 5 9 no noProtege (ev3) 20 80 6 9 no no

Stents.Carotid Wallstent (Boston Scientific, Natick, MA). When

the carotid Wallstent is implanted in a vessel, it ismuch longer depending upon the degree of com-pression. During deployment, it foreshortens accord-ing to the diameter of the vessel. It comes insizes of 6–10 mm in diameter and 30–50 mm inlength.

The stent mesh design provides high plaque cover-age. A constant radial force prevents collapsing of thestent and allows embedding of the stent in the vesselwall. It adapts to the changing diameter of the vesselacross the bifurcation. A disadvantage is that the stentstraightens the vessel more than open cell nitinol stentsdo.

Exponent (Medtronic, Minneapolis, MN). The carotidnitinol open cell design stent has a monorail systemand is 0.014′′ wire compatible. It is available in a di-ameter of 6–10 mm and has a length of 20–40 mm. With

Table 5. Cerebral Protection Devices

Cerebral Protection Filter/Balloon MicroporesSystem (mm) (µ)

Angioguard (Cordis) 4–8 100Emboshield (Abbott) 3–6 140E.P.I. XP (Boston Scientific) 3.5–5.5 80E.P.I. EZ (Boston Scientific) 3.5–5.5 110AccuNet (Guidant) 4.5–7.5 115Spider (ev3) 3–7 50–200Rubicon (Rubicon) 4–6 100Interceptor (Medtronic) 4.5–6.5 100PercuSurge (Medtronic) 3–6 0Parodi AES (ArteriA Occlusion of ACC/ACE 0

Medical Science)MO.MA (Invatec) Occlusion of ACC/ACE 0

the exponent stent foreshortening of less than 10% canbe observed.

Xact Carotid Stent (Abbott, Abbott Place, IL). The Xactstent is a nitinol stent that comes in two different shapes.The straight stent is available in a diameter of 7–10 mmand a length of 20–30 mm. The Xact stent has a closedcell design and therefore it is stiffer than other nitinolstents. It should be deployed only in a straight vesselsegment.

RX Acculink (Guidant, Indianapolis, IN). This open cellnitinol stent is also available in two different shapes.The straight stent comes in a diameter of 5–10 mm andhas a length of 20–40 mm and the tapered stent has adiameter of 6–8 mm and 7–10 mm. It comes in a lengthof 30 and 40 mm.

Sinus-Carotid (OptiMed, Ettlingen, Germany). This niti-nol stent is another stent which is available in twoconfigurations. The straight stent has a diameter of5–9 mm and a length of 20–40 mm. The taperedstent comes in a diameter of 6–9 and 7–10 mm andhas a length of 40 mm. It has an open cell de-sign. A special feature is that the stent is attached tothe delivery system until the end of the release pro-cess which prevents the stent from “jumping distally”during deployment. It is mounted on a 5F deliverysystem.

NexStent (Endotex, Cupertino, CA). This stent is avail-able in just one size which fits into all vessels with adiameter of 4–9 mm and has a length of 30 mm. Ithas a closed cell design which prevents entrapment ofballoons and filters. It is much more flexible becauseunlike other closed cell design stents it is made of arolled nitinol sheet. It has a tip which is formed bythe delivery sheath instead of the delivery shaft. Thisfacilitates removal of the delivery system after stentimplantation.


RESULTS OF CAS

Conformexx (Bard, Murray Hill, NJ). The ConformexxStent is available in a diameter of 6–12 mm and a lengthof 20–40 mm. This is the only self-expandable nitinolstent that is available with a diameter of more than 10mm. The tip of the delivery system is formed by thesheath and not by the shaft.

Precise (Cordis, Miami Lakes, FL). This open cell niti-nol stent has a diameter of 5–10 mm and a length of20–40 mm. The stent struts are shorter compared toother stents. This gives a high flexibility and good wallcoverage.

Zilver Stent (Cook, Bloomington, IN). The Zilver stenthas a diameter of 5–9 mm and a length of 20–60 mmdepending on the size of the diameter of the stent. Itis made of nitinol and has an open cell design. It ismounted on a 5F delivery system.

Protege GPS (ev3, Plymouth, MN). This nitinol stent hasa diameter of 6–9 mm and a length of 20–80 mm asit can also be used in peripheral procedures. The stentdoes not shorten during the implantation. The ExactPlacement Release Technology avoids premature stentdeployment.

Cerebral Protection Devices. A major limitationof carotid angioplasty is distal embolization during theprocedure. Balloon dilatation, stent implantation, andmanipulation of the vessels through catheters and wiresrelease embolic debris, which can cause severe damage.Therefore, in almost all centers, embolic protection de-vices are applied routinely. Unfortunately, there are norandomized trials comparing CAS with protection toCAS without cerebral protection. However, many se-ries and registries revealed a benefit of protection de-vices.

The world registry described a perioperative strokeand death rate of 5.29% in patients without and of2.23% in procedures with protection.19

Kastrup et al.24 reviewed trials from 1990 to 2002with a total of 2,537 procedures performed without pro-tection devices, and 896 CAS procedures performedwith an embolic protection device. The combinedstroke and death rate at 30 days in patients treated withcerebral protection was 1.8% compared with 5.5% inpatients treated without cerebral protection devices.

There are three different types of embolic protectiondevices: filters, distal occlusion balloons, and proximalocclusion balloons.

Filters and distal occlusion balloons are introducedafter sheath placement. Placement in tortuous vesselsmay be difficult. In these cases a proximal embolicprotection system should be preferred. Although the

crossing profile of the current available filters is al-ready acceptable low in a tight and calcified lesion, thedeployment of a distal occlusion balloon with a cross-ing profile of 2.7F or a proximal embolic protectionsystem may be more suitable.

All filters except the Rubicon filter are introducedthrough a delivery catheter which is introduced throughthe sheath. After opening of the filter, the retrievalcatheter is removed. The filter wire can be used as aguide wire for balloon dilatation and stent implanta-tion.

When having chosen a distal occlusion balloon, thedebris has to be removed through aspiration before de-flating of the balloon.

Proximal embolic protection systems as there are theMO.MA and the Parodi device occlude the external andthe common carotid artery with an occlusion balloon.Through the guiding catheter carotid angioplasty canbe performed as usual. As with the distal occlusionsystems the debris has to be aspirated before deflatingthe occlusion balloons after angioplasty.

Angioguard XPTM (Cordis, Miami Lakes, FL). The An-gioguard filter was the first filter which became avail-able. The Angioguard XPTM is the new version of thisfilter. It consists of the filter itself and a retrieval catheter(5.1F). The filter comes in diameters between 4 and 8mm.

The filter membrane is made of polyurethane. Thepores in the filter have a diameter of 100 µm. Thefilter has 8 nitinol struts. Four of these struts have aradiopaque marker.

E.I.FilterWireTM (Boston Scientific, Natick, MA).The newest generation of the E.P.I. FilterWireTM, theFilterWire EZTM (Boston Scientific, Natick, MA), ismounted on a 0.014′′ wire by means of a radiopaquenitinol wire loop. To improve the alignment to the ves-sel wall, the wire is kept in the center of the filter by ahorizontal strut. It has a freely rotating frame and filter.

The filter comes in one size and adapts to vesseldiameters between 3.5 and 5.5 mm.

The older generation of the E.P.I. FilterWire wasan eccentric filter, which occasionally had to berepositioned to achieve full apposition to the vesselwall.

MedNova EmboShield Cerebral Protection System(Abbott, Abbott Place, IL). The newest version of thisfilter is the fourth generation. It consists of a guidewire, a delivery catheter (3.7–3.9F), a filter basket(3–6 mm), and a retrieval catheter (6F). The basket has apore free zone that helps preventing embolic extrusion


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and a helical staggered pore design to help optimizethe capture efficiency. The hydrophilic coating of thefilter is intended to minimize platelet, fibrin, or RBCadhesion.

SpiderTM (ev3, Plymouth, MN). The Spider device is theonly filter which allows usage of a wire of the opera-tors’ choice to cross the lesion. The filter consists of aNitinol basket at the tip of a 0.014′′ wire. The “pores”in the basket have a size between 50 and 200 µm. Thediameter of the basket ranges between 3 and 7 mm. Aclasp at the entrance of this filter ensures a better vesselwall apposition of the opening of the filter.

Interceptor (Medtronic, Minneapolis, MN). The Inter-ceptor filter consists of a nitinol basket attached toa 0.014′′ steerable guide wire. The basket diameterranges between 4.5 and 6.5 mm. The size of the poresis 100 µm.

AccuNetTM Embolic Protection Device (Guidant, Indian-apolis, IN). This is a polyurethane filter with a nitinolbasket of a diameter ranging from 4.5 to 7.5 mm. Thewire can be rotated independently from the basket. Thedouble-strut filter has four radiopaque platinum mark-ers for visibility. The pore size is 115 µm.

Rubicon Filter (Rubicon, Salt Lake City, UT). The Rubi-con filter is the only filter without a delivery catheter.Therefore, it has a low profile of 2.0–2.4F. It is mountedon a 0.01411 guide wire. The micropores have a sizeof 100 µm. The Nitinol filter is available in size of4–6 mm. The long taper design of the filter increasesthe volume of the filter. It has a retrieval system actu-ator, which shows the exact status of the filter as it isbeing captured for removal. To minimize snagging ofthe stent it has a dilator-style inner sheath and to min-imize the filter movement during filter retrieval, thereare telescopes over the filter basket.

Occlusion Devices

Percusurge GuardWireTM (Medtronic, Minnea-polis, MN). This was the first occlusion device whichwas available commercially. It is designed to containand aspirate embolic material during the procedure.The balloon can be filled through a lumen inside of thewire up to a diameter between 3 and 6 mm.

After crossing the lesion with the GuardWire, theocclusion balloon is inflated distal of the stenosis toocclude the internal carotid artery. After stent im-plantation, an aspiration catheter is advanced over thewire of the occlusion system into the internal carotid

artery. The debris, which has been dislodged from theatheroma is aspirated with a syringe and removed.Thereafter, the distal occlusion balloon is deflated.

Parodi AES (ArteriA Medical Science, SanFrancisco, CA).17 This device prevents distal em-bolization by establishing a retrograde flow in the inter-nal carotid artery. It consists of a 10F guiding catheterwith a balloon at its distal tip. This balloon is inflated inthe common carotid artery. To avoid blood flow fromthe external to the internal carotid artery the exter-nal carotid artery is occluded with a separate balloonmounted on a wire which is introduced through the lu-men of the guiding catheter. The proximal hub of theguiding catheter is connected with a venous sheath.Due to the pressure difference between the distal inter-nal carotid artery and the venous system, a retrogradeblood flow is established. A filter located in the arteri-ovenous shunt prevents embolization of the debris intothe venous system.

MO.MA (Invatec, Roncadelle, Italy). TheMO.MA device is a “proximal flow blockage” cere-bral protection device. Cerebral protection occurs byinterruption of antegrade blood flow from the commoncarotid artery and retrograde blood flow through theipsilateral external carotid artery. This is achieved bya low-pressure balloon occlusion of the two vessels bymeans of a single device integrating the two occlusiveballoons and a working channel for the delivery ofinterventional devices to the target lesion. One balloonoccludes the external carotid artery and the secondballoon the common carotid artery, so that it is avoidedto pass the target lesion with the embolic protectionsystem before starting the procedure.

Debris are thus stopped at the carotid bifurcation andprevented from dislodging to the brain. Removal of de-bris is performed by spot (active) syringe aspirationwhich can be performed any time during the interven-tion through the working channel of the device.

Long-Term Results of CAS

Currently, the results of only two randomized tri-als are available. The CAVATAS trial was published in2001 reporting the stroke and death rate after 3 years.13

This year, the 2-year results of the SAPPHIRE trialwere presented.15

The CAVATAS trial compared the results of surgeryto endovascular treatment after 3 years. It describesthe rate of death or disabling stroke in any territory


RESULTS OF CAS

of 14.3% in the endovascular group and of 14.2% inthe surgical group. Obviously, this trial points out thatcarotid stenting and endarterectomy are comparableconcerning the long-term results. The complication rateis higher than in the NASCET trial as well as in theECST trial due to the higher risk patients included.13

The 1-year results of the SAPPHIRE trial confirm thetrend, which was already visible in the 30-day results.The death, stroke, and myocardial infarction rate was19.9% in the surgical arm and 11.9% in the endovas-cular arm. At 2 years the rate of major adverse eventswas 25.2% in the endarterectomy group and 18.4% inthe interventional group.15

Wholey et al. reported in their world registry arate of neurological events including TIA, stroke, andneurological-related death of 2.8% during the 6- to 12-month follow-up period, which was available for 3,924patients (84%).25

In their report on the results of 513 patients, Wholeyet al. described a 3-year freedom from all fatal and ip-silateral nonfatal strokes excluding the 30-day peripro-cedural period of 95.0% for balloon-mounted stentsand 95.2% for self-expandable devices during a meanfollow-up of 20.6 months (range: 5.6 years).26 The neu-rological event rate was 1.3%, 1.3%, and 1.7% at 1-, 2-,and 3-year follow-up in the updated review by Wholey,published in 2003.19

Roubin et al. described in their 5-year prospectiveanalysis a 3-year freedom from all fatal and nonfatalstrokes of 88 ± 2% and taking into account only thosepatients who survived the 30-day periprocedural pe-riod, a 3-year freedom of 95 ± 2%. During follow-up,3.2% of the patients developed a stroke.20

The complication rate during long-term follow-upvaries between 5% and 20% in the surgical arm ofthe trials and between 3% and 12% in the stentingarms.15,19,20,26

Restenoses

Because restenosis is a common adverse event dur-ing follow-up in all vascular interventions, it was fearedthat it may limit the long-term results of CAS. However,it is not observed frequently in carotid lesions. Severalauthors reviewing larger series of carotid stenting re-ported a restenosis rate between 2.27%12 and 4.9%.27

Wholey reported a restenosis rate of 2.7% at 12 monthsand of 5.6% at 48 months.19 In the angioplasty patientsof the CAVATAS trial, a restenosis was observed in

18% versus 5% in endarterectomy patients.13 This highrate of restenosis can probably be explained due to thelow number of stents implanted and the use of balloonexpandable stents.

Discussion

After initial controversial discussions, CAS is evolv-ing as an alternative to carotid endarterectomy. Thefirst two randomized trials, CAVATAS and SAPPHIRE,comparing both techniques revealed equality of stent-ing and surgery. Taking myocardial infarction into ac-count as an endpoint, high-risk patients benefit morefrom CAS.

Several series and one-armed trials presented a lowcomplication rate, which should decrease even moredue to more experienced operators and the improve-ment of the endovascular method. The technical suc-cess already today is high. Further development of cere-bral protection devices should establish stenting as astandard procedure not only for high-risk symptomaticpatients.

Many patients tend to favor stenting, which is lessinvasive, to surgery, because it does not have the riskof anesthesia. Cranial nerve palsy and scars can beavoided.

To prove durability of CAS and to ensure lasting re-sults in younger patients, long-term results over 5 yearsand longer are needed. The first series reporting onthese results present a low complication and restenosisrate. Still, more randomized trials with a long follow-upare necessary to gain a broader acceptance of stentingand to make it available for all patients with cerebrovas-cular disease.

References

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2. Mathias K, Jager H, Hennigs S, et al. Endoluminal treatment ofinternal carotid artery stenosis. World J Surg 2001;25:328–334.

3. Theron J, Courtheoux P, Alachkar F, et al. New triplecoaxial catheter system for carotid angioplasty with cere-bral protection. AJNR Am J Neuroradiol 1990;11(5):869–874.

4. North American Symptomatic Carotid Endarterectomy TrialCollaborators. Beneficial effect of carotid endarterectomy insymptomatic patients with high-grade carotid stenosis. N EnglJ Med 1991;325:445–453.


RABE AND SIEVERT

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11. Chaturvedi S, Aggarwal R, Murugappan A. Results of carotidendarterectomy with prospective neurologist follow-up. Neu-rology 2000;5:769–772.

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13. Brown MM. Endovascular versus surgical treatment in patientswith carotid stenosis in the Carotid and Vertebral Artery Trans-luminal Angioplasty Study (CAVATAS): A randomized trial.Lancet 2001;357(9270):1729–1737.

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17. Whitlow PL. SECURITY: Multicenter evaluation of carotidstenting with a distal protection filter. Transcatheter Cardio-vascular Therapeutics, 15th Annual Symposium, Washington,USA, September 15–19, 2003.

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20. Roubin GS, New G, Iyer SS, et al. Immediate and lateclinical outcomes of carotid artery stenting in patientswith symptomatic and asymptomatic carotid artery steno-sis: A 5-year prospective analysis. Circulation 2001;103:532–537.

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Carotid Artery Stenting: : State of the Art