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  • 1. The American Journal of Surgery 195 (2008) 259 –269 Review Endarterectomy or carotid artery stenting: the quest continues Michiel G. van der Vaart, M.D.a, Robbert Meerwaldt, M.D., Ph.D.b, Michel M.P.J. Reijnen, M.D., Ph.D.c, René A. Tio, M.D., Ph.D.d, Clark J. Zeebregts, M.D., Ph.D.a,* a Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, 9700 RB Groningen, The Netherlands b Department of Surgery, Isala Clinics, Zwolle, The Netherlands c Department of Surgery, Alysis Zorggroep, Lokatie Rijnstate, Arnhem, The Netherlands d Department of Cardiology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands Manuscript received May 24, 2007; revised manuscript July 3, 2007 Abstract Background: Carotid endarterectomy (CEA) is still considered the “gold-standard” of the treatment of patients with significant carotid stenosis and has proven its value during past decades. However, endo- vascular techniques have recently been evolving. Carotid artery stenting (CAS) is challenging CEA for the best treatment in patients with carotid stenosis. This review presents the development of CAS according to early reports, results of recent randomized trials, and future perspectives regarding CAS. Methods: A literature search using the PubMed and Cochrane databases identified articles focusing on the key issues of CEA and CAS. Results: Early nonrandomized reports of CAS showed variable results, and the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy trial led to United States Food and Drug Administration approval of CAS for the treatment of patients with symptomatic carotid stenosis. In contrast, recent trials, such as the Stent-Protected Angioplasty Versus Carotid Endarterectomy trial and the Endarterectomy Versus Stenting in Patients with Symptomatic Severe Carotid Stenosis trial, (re)fuelled the debate between CAS and CEA. In the Stent-Protected Angioplasty Versus Carotid Endarterectomy trial, the complication rate of ipsilateral stroke or death at 30 days was 6.8% for CAS versus 6.3% for CEA and showed that CAS failed the noninferiority test. Analysis of the Endarterectomy Versus Stenting in Patients With Symptomatic Severe Carotid Stenosis trial showed a significant higher risk for death or any stroke at 30 days for endovascular treatment (9.6%) compared with CEA (3.9%). Other aspects–such as evolving best medical treatment, timely intervention, interventionalists’ experience, and analysis of plaque compo- sition–may have important influences on the future treatment of patients with carotid artery stenosis. Conclusions: CAS performed with or without embolic-protection devices can be an effective treatment for patients with carotid artery stenosis. However, presently there is no evidence that CAS provides better results in the prevention of stroke compared with CEA. © 2008 Excerpta Medica Inc. All rights reserved. Keywords: Carotid endarterectomy; Embolic-protection device; Stenting; Stroke preventionStroke and stroke-related death are increasing causes of event, first-year survivor are €18,517 (USD $25,016)/concern in the western world. Currently, stroke is the third patient, and lifetime costs are €43.129 (USD $58,257)/most common cause of mortality [1,2]. A Swedish publica- patient. This in turn accounts for 3% to 4% of total healthtion showed for the first time a stroke incidence of 213/ care costs in several European countries [4]. The estimated100,000 persons annually [3]. This generates an enormous direct and indirect cost generated so far by stroke in 2007 infinancial burden to the western society, as shown by a the United States is USD $62.7 billion [2].German cost analysis [4]. Direct medical costs for a first- Extracranial cerebral atherosclerosis causes 8% to 29% of all ischemic strokes [5]. Thrombotic emboli arising from cardiac origin are another more frequent cause of ischemic * Corresponding author. Tel.: 011-31-503613382; fax: 1-31-503611745. strokes [6 – 8]. The aim of treatment for patients with carotid E-mail address: stenotic disease lies in decreasing the risk of disabling0002-9610/08/$ – see front matter © 2008 Excerpta Medica Inc. All rights reserved.doi:10.1016/j.amjsurg.2007.07.022
  • 2. 260 M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269stroke or stroke-related death as consequences of thrombo- this previously largely unfounded practice [13–15,32]. Theembolism. Different medical-treatment strategies evolved European Carotid Surgery Trial (ECST) and the Northfrom studies initially aimed at treating patients with cardio- American Symptomatic Carotid Endarterectomy Trialvascular disease. For a long time, treatment consisted of 2 (NASCET) are the 2 most-referred trials on the subject ofmain modalities: medication and/or open surgery (carotid the treatment of patients with symptomatic carotid stenosis.endarterectomy [CEA]) [9 –12]. For most patients with ca- Inclusion criteria consisted of patients who had had a tran-rotid stenosis, surgical endarterectomy, rather than medical sient ischemic attack or nondisabling stroke in the internaltreatment, became the treatment of choice for stroke pro- carotid flow tract 6 months before enrollment. Despitephylaxis, with proven efficacy. Symptomatic patients who differences in carotid stenosis analysis, both trials came tohave carotid stenoses between 50% and 99% and perioper- the same conclusions [15]. Findings in the NASCET dem-ative rates of stroke and/or death 6% are best treated by a onstrated a decreased 2-year stroke risk from 26% in thecombination of best medical treatment (BMT) and surgery medical group to 9% in the CEA group, yielding an absoluteaccording to guidelines of the American Heart Association risk reduction of 17% (for patients with 70% carotidand results of large randomized trials [12–16]. The Asymp- stenosis). Perioperative risk rates for stroke and/or deathtomatic Carotid Atherosclerosis Study (ACAS) concluded were 5.8% in the surgical arm. Patients in this study whothat also asymptomatic patients with a carotid artery steno- had undergone surgical correction of high-grade stenosissis 60% are good candidates for CEA, with a reduced gained a durable benefit lasting 8 years [33]. It was further5-year ipsilateral stroke risk. Especially for this category of found that the efficacy of CEA increased with increasingpatients, CEA should be performed with low morbidity and degree of stenosis, previous stroke presentation, and pres-mortality rates in order to achieve a considerable risk re- ence of ulceration. Furthermore, the presence of diabetes,duction warranting the risks of the operation [17]. The coronary heart disease, or hypertension increased stroke riskAmerican Heart Association therefore recommended that in the medically treated group but not in the CEA group.(grade A) CEA be performed in asymptomatic patients with The ECST showed a decrease in the 3-year risk of strokea carotid stenosis of 60% to 99% if perioperative risk rates and/or death from 26.5% in the medical group to 14.9% inare 3% and if the patient has a life expectancy 5 years the CEA group. Interestingly, the early (30-day) rates of[1,12]. Results from these studies are discussed in detail stroke and/or death were higher in women (10.6%), inlater in this review. Results, as shown by Mullenix et al patients with systolic blood pressure 180 mm Hg (12.3%),[18], show that CEA is a safe, effective, and durable treat- and in patients with peripheral vascular disease (12.3%).ment even when not performed in “high-volume” CEA From the results of the pooled data (6,092 patients), acenters [18]. significant 16% absolute risk reduction during 5 years Despite the proven efficacy of CEA, great interest has (numbers needed to treat 6.3) was shown for symptomaticbeen generated in carotid angioplasty and stenting (CAS) as patients with a stenosis 70% (without near occlusion). Aan alternative to surgical therapy. The assets of CAS seem 4.6% absolute risk benefit was shown for patients with aobvious in patients with hostile necks because of previous 50% to 69% stenosis (numbers needed to treat 22). Overallsurgery and/or radiotherapy [19]. Moreover, CAS is less operative risk of stroke and/or death within 30 days afterinvasive compared with CEA and has decreased risk for surgery was 7.1%. For patients with near occlusion, thecranial nerve damage as well as the ability to treat lesions absolute risk reduction was 5.6% during 2 years (P .19),that are beyond the reach of CEA [20]. During the last and 1.7% during 5 years (P .9). Others have debated thedecade, several trials and series have been published com- benefit of CEA in patients with near occlusion. For exam-paring CAS with CEA [21–29]. The aim of this article is to ple, Fox et al [34] showed no apparent benefit of CEA inreview the literature concerning the results of CAS and to patients with near occlusion. The absolute risk reduction inelucidate on its current status. In addition, future options are the near-occlusion group was 4.2% compared with 17.8% indiscussed. those with severe stenoses but without near occlusion [34]. With near occlusion, there is relative protection against emboli because arterial diameter is decreased, and this mayMethods in part explain the relatively low long-term stroke risk in A literature search using the PubMed and Cochrane these patients. Numerous posthoc analyses of subgroupsdatabases identified articles focusing on the key issues of from the NASCET and the ECST have been published, butCEA and CAS. Manual cross-referencing was also per- they are beyond the scope of this review article.formed, and relevant references from selected papers were Other studies, such as the Asymptomatic Carotid Ath-reviewed. erosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST), were designed to investigate whetherHistory patients with asymptomatic stenotic lesions were eligible The first successful extracranial CEA (ICEA) procedure for CEA [35,36]. In ACST, a total of 3,120 asymptomaticwas performed in 1953. However, it took almost 20 years patients with stenotic lesions 60%, as seen on duplexbefore the results for therapy of patients with (symptomatic) Doppler ultrasound, were included. The 5-years risk forinternal carotid artery (ICA) stenosis were reported [30,31]. stroke (minor and major) in surgical patients was 6.4%In the 1980s, CEA was the most-performed vascular pro- versus 11.8% for patients who deferred surgery. Conse-cedure. It was not until the last two decades of the 20th quently, a significant absolute risk reduction of 5.4% wascentury that results from large randomized controlled trials noted, although a subgroup analysis showed clear benefitsconsidering BMT versus surgery were published supporting only for patients 75 years old. Fifty percent of people
  • 3. M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269 261Table 1Early carotid stent series dataAuthor Year n Symptomatic Technical success Morbidity and mortality rate Stroke rate (%) stenosis (%) rate (%) (30-day; %)Roubin et al [50] 2001 528 52 98 7.4 5.8Theron [43] 1996 69 NS 100 3 NSBergeron et al [49] 1999 99 58 97 7.1 1Diethrich et al [46] 1996 110 38 99 7.3 6.5Waigand [126] 1998 50 28 100 2 4Yadav et al [29,47] 1997 107 64 100 7.9 8.4Vozzi [127] 1997 22 45 96 9 9Wholey et al [44,57] 1997 108 56 95 5.5 3.6Henry et al [51] 1998 163 65 99 5.2 3Teitelbaum et al [52] 1998 22 68 100 27.3 24 NS not specified.older in age died of unrelated causes 5 years of follow-up. suitable to treat patients with severe concomitant cardiacFurthermore, the efficacy of CEA in women compared with and/or pulmonary disease. Other advantages include easymen was also one-third less based on higher perioperative access in patients with hostile necks because of previousrisks in women. Overall operative risk of stroke and/or surgery and/or radiotherapy. In addition, patients whosedeath within 30 days after surgery was 3.1%. The ACAS stenoses extended onto the base of the skull were accessiblehad similar results: There was risk reduction of 5.9% in for treatment.surgical patients with a stenosis 60%. The 2.3% operative Risk of embolic stroke limited early enthusiasm. Initialrisk of stroke and/or death in this trial was low. Approxi- strategies focused on neurologic rescue by fibrinolyticmately 50% of the strokes in the CEA arm were related to agents or techniques to remove embolic debris. Later treat-the surgical procedure, whereas the others were related to ment shifted from rescue to protection. Most of the resultscontrast arteriography. The ASA and Carotid Endarterec- of carotid PTA proved promising, with rates of stroketomy randomised controlled trial published in 2003, which and/or death ranging between 0% and 7.9%, but most stud-compared periop erative complications with CEA depend- ies were rather small and nonrandomized (Table 1) [43,ing on different acetylsalicylic acid dosages, disclosed a 44,46,47,49 –52,126,127]. Inclusion and exclusion criteriaperioperative complication risk of 4.6% [37]. Notable, re- were diverse, and PTAs were randomly carried out with orsults from the ACAS trial show that 20 CEAs would be without stenting. PTA alone had its limitations because ofneeded to prevent 1 stroke in 5 years of follow-up. Two its decreased (long-term) durability, but the use of a stentanalyses performed afterwards showed that despite the high certainly did not rule out possible danger. Problems re-numbers needed to treat, CEA in asymptomatic patients is ported were direct recoil of the vessel wall after dilatation,cost-effective [38,39]. increased embolism caused by catheter manipulation (4 Guidelines for performing CEA were distilled by the times greater compared with CEA), severe bradycardia, andAmerican Heart Association from these data. In symptom- hypotension after balloon dilatation and dissection [21,atic patients, the risk of stroke and/or death resulting from 53,54]. Intermingled with these reports, changes in tech-treatment by CEA should be 6% and for asymptomatic nique, especially the introduction of embolic-protection de-patients should be 3% [40]. vices (EPDs), took place.Endovascular treatment for carotid stenosis CAS technique and embolic protection devicesEarly reports Presently, having the patient under local anesthesia is the As a result of the widespread use of angioplasty and preferred way of performing CAS because, in this way, thestenting in the treatment of patients who have arterial ste- patient’s neurologic condition can be monitored continu-nosis in the context of coronary artery disease, treatment of ously [55]. Access is gained by way of the common femoralpatients with peripheral stenotic arterial vascular disease artery to perform selective catheterization of the commonalso evolved. With the advancing techniques of percutane- carotid artery. Recognition of normal and variant anatomyous transluminal angioplasty (PTA), treatment of patients of the aortic arch and the cervicocerebral circulation iswith carotid stenosis also became feasible. The first balloon required for successful performance of angiography andangioplasty for carotid stenosis was performed in 1979, and CAS. Selective angiography of both carotid arteries is rec-reports in the 1980s included balloon occlusion to decrease ommended before CAS to evaluate carotid stenosis severity,embolic complications [41– 43]. Meanwhile, carotid artery morphology, carotid tortuosity, calcification, intracranialstenting has been presented in an increasing variety of circulation stenosis, collateral circulation, and malforma-publications as a viable alternative to CEA in the treatment tions. Because there is a risk of embolization caused byof patients with extracranial carotid stenosis [43–50]. Sev- manipulation during the procedure, EPDs are increasinglyeral arguments have been brought forward to advocate its being used [56]. No randomized trials have compared CASuse. The minimally invasive nature of the procedure made it with EDPS versus CAS without EPDs. However, the avail-
  • 4. 262 M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269ability of EPDs seems to decrease the risk of embolic Table 2complications as described by the carotid artery stent reg- Carotid artery stent registriesistries [57,58]. Importantly, many other studies have not Registry N (% symptomatic) Combined MI/stroke/death rate (%)been powered to show a benefit from EPD. 30 d 1y Three different approaches to achieve protection havebeen used: (1) distal balloon occlusion, (2) distal filter BEACH 480 (25.3) 5.8* (1.0/4.4/1.5) 9.1# (1.1/7.0/3.2)placement, and (3) proximal occlusion with flow reversal ARCHeR 581 (23.8) 8.3* (2.4/5.5/2.1) 9.6* (0/1.3/0)[56,59]. Although all distal EPDs are able to capture and CABERNET 454 3.8# 11.5#remove embolic debris, this does not eradicate embolic CAPTURE 3,500 (13.8) 5.7* (.9/4.8/1.8) NAcomplications. Inability to deliver or deploy the EPD, EPD- CREATE 543 (17.4) 6.2* (1.0/4.5/1.9) NA MAVerIC 498 5.3# NAinduced vessel injury, ischemia caused by occlusion, and SECuRITY 398 (21) 8.5# (.7/6.9/.9) NAincomplete embolic debris removal may all result in em- CaRESS 143 (31) 2.1* (0/2.1/0) 10 (1.7/5.5/6.3)bolic cerebral complications. Microporous filters are posi- CREST 749 (30.7) 4.4* (0/4.0/.8) NAtioned in the ICA distal to the target lesion. The filter is MO.MA 157 (19.7) 5.7* (0/5.1/.6) NAconstrained with a delivery sheath to pass the carotid ste- PRIAMUS 416 (63.5) 4.6* (0/4.1/.5) NAnosis. Once in position, the delivery sheath is withdrawn to ARCHeR Acculink for Revascularization of Carotids in High-Riskdeploy the filter. Filters offer the advantage of continued Patients; CABERNET Carotid Artery Revascularization Using Bostoncerebral perfusion. In contrast, the delivery system is rela- Sci EPI Filterwire EX/EZ and EndoTex NexStent; CAPTURE Carotidtive large, which may interfere with crossing the stenosis, Acculink/Accunet Postapproval Trial to Uncover Rare Events; CaRESSand the stiffness of the system may be a problem in tortuous Carotid Revascularization Using Endarterectomy or Stenting Systems;vessels, increasing the risk of embolization during place- CREATE Carotid Revascularization With ev3 Arterial Technologyment of the filter. Occlusion balloons offer the advantage of Evaluation; MI myocardial infarction; MAVerIC Endarteractomylower device-crossing profiles, but they still require cross- Versus Angioplasty in Patients With Severe Symptomatic Carotid Steno-ing the stenosis as well as interruption of cerebral perfusion. sis; MO.MA Multicenter Registry to Assess the Safety and Efficacy ofOnce protection has been secured, the stent is put into place the MO.MA Cerebral Protection Device During Carotid Stenting; NAunder angiographic control. Stents used are mostly self- not available; PRIAMUS Proximal Flow Blockage Cerebral Protection During Carotid Stenting; SECuRITY Registry Study to Evaluate theexpanding, but balloon-expandable stents can be used when NeuroShield Bare Wire Cerebral Protection System and X-Act Stent intreating the ostium of the common carotid artery [55]. After Patients at High Risk for Carotid Endarterectomy.the stent is put in place, postdilatation is applied, followed * Data available from publications in peer-reviewed control angiogram. A perfect anatomic end result at # Data from: or is not pursued (most studies accept residualstenosis 30%) because aggressive balloon dilatation ap-pears to increase the risk of complications, and residual stroke, and/or death at 30 days. The primary end point ofstenosis is mostly related to calcification, which often does efficacy was the incidence of ipsilateral stroke betweennot resolve with repeated dilatations [60]. The entire pro- 30 days and 1 year. These registries did not include acedure is performed with antiplatelet therapy, which in most control group.patients is achieved with a combination of acetyl salicylic Technical success was achieved in most studies in 97%acid and clopidogrel. Clopidogrel is stopped 6 weeks after of all patients. The incidence in 30-day myocardial infarc-the procedure, but acetyl salicylic acid is continued indefi- tion, stroke, and/or death varied between 2.1% and 8.3%nitely thereafter. [61– 63,65– 67]. Unfortunately, most registries did not dif- ferentiate between symptomatic and asymptomatic patientsProspective multicenter registries when analyzing results. However, the BEACH trial did and Compared with the early CAS series previously de- showed a composite end point of 7.9% in symptomaticscribed (Table 1), prospective registries with predefined patients (mortality 0.1%, stroke 7.4%, and myocardial in-inclusion and exclusion criteria, independent neurologic as- farction 1.1%) and 5.0% in asymptomatic patients (mortal-sessment, and oversight committees were designed to fur- ity 1.6%, stroke 3.4%, and myocardial infarction 0.7%).ther assess safety and United States Food and Drug Admin- Importantly, other registries showed that independent pre-istration approval of CAS with EPDs in high-risk patients dictors of stroke or death at 30 days included symptomatic(Table 2). High-risk surgical patients were defined as (eg, carotid stenosis, duration of filter deployment, and baselinethe Boston Sci EPI: A Carotid Stenting Trial for High-Risk chronic renal failure. Most registries have not yet been peerSurgical Patients [BEACH] trial) those with a surgically reviewed, but they have been presented at internationalinaccessible lesion, previous head and/or neck radiation, meetings, so results are preliminary.spinal immobility, restenosis after CEA, laryngeal palsy,tracheostoma, contralateral carotid stenosis, age 75 years,severe comorbidity, planned coronary bypass, or history of Initial randomized controlled trials comparingmajor surgery [61– 64]. The most common high-risk sur- CAS with CEAgery categories observed were anatomic criteria or previous The Leicester study was the first prospective randomizedCEA. Most registries were conducted to acquire United States singe-center trial investigating CAS versus CEA in symp-Food and Drug Administration or Conformité Européene (CE; tomatic patients [21]. The trial enrolled symptomatic low-Europe) approval. The primary safety end point was risk patients with carotid stenoses 70%. However, theusually the combined rate of myocardial infarction, study was terminated after allocation of only 17 partici-
  • 5. M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269 263Table 3Randomized trials of CAS versus CEATrial n Patients Primary end point Results (%)Leicester 17 Low-risk symptomatic 30-d stroke and/or death CAS 70 CEA 0Wallstent 219 Low-risk symptomatic 1-y stroke and/or death CAS 10.4 CEA 4.4SAPPHIRE 334 High-risk (a)symptomatic 30-d MI, stroke, and/or death (1-y stroke or death) CAS 12.2 CEA 20.1Kentucky 1 104 Low-risk symptomatic 30-d stroke and/or death CAS 1.8 CEA 1.9Kentucky 2 84 Low-risk asymptomatic 30-d stroke and/or death CAS 0 CEA 0CAVATAS 504 Low-risk (a)symptomatic 30-d stroke and/or death (3-y stroke) CAS 10.0 CEA 9.9SPACE 1,183 Low-risk symptomatic 30-d stroke and/or death CAS 6.8 CEA 6.3EVA-3S 527 Low-risk symptomatic 30-d stroke and/or death (4-y stroke) CAS 9.6 CEA 3.9CREST 2,500 Low-risk (a)symptomatic 30-d MI, stroke, and/or death (4-y stroke) Active enrollmentICSS 1,500 Low-risk symptomatic 30-d MI, stroke, and/or death (3-y stroke) Active enrollmentACT 1,540 Low-risk asymptomatic 30-d MI, stroke, and/or death (1-y stroke) Active enrollmentACST 5,000 Any risk asymptomatic 30-d MI, stroke, and/or death (1-y stroke) Active enrollment ACT Asymptomatic Carotid Stenosis Versus Endareterectomy Trial; CAS carotid artery stenting; CAVATAS Carotid and Vertebral ArteryTransluminal Angioplasty Study; CEA carotid endarterectomy; ICSS International Carotid Stenting Study; MI myocardial infarction.pants. Interim analysis showed that 70% of all patients in The run-in phase analysis from the Carotid Revascular-the CAS arm had neurologic complications. In contrast, ization Versus Stent Trial (CREST) focused on patient ageCEA was performed uneventfully (Table 3). and periprocedural risk for patients receiving CAS. Four The Carotid and Vertebral Artery Transluminal Angio- patient-age categories were created: 60 years, 60 to 69plasty Study was an international multicenter randomized years, 70 to 79 years, and 80 years. Risk of stroke or deathtrial with 504 patients, but it lacked strict inclusion and increased with age, but this was seen mainly in octogenar-exclusion criteria [27]. Major outcomes within the first 30 ians (12.1%) [24]. Risk was not mediated by adjustment fordays of treatment, defined as any disabling stroke or death, symptomatic status, use of antiembolic devices, sex, orshowed no significant difference between CAS and CEA percentage of stenosis. Notably, patients 80 years were(10.0% vs 9.9%). Noteworthy, only 26% of patients treated not excluded from actual randomization within CREST.endovascularly received a stent. At 1-year ultrasound fol- Carotid artery stenosis is relatively frequent in older pa-low-up, severe restenoses (70% to 90%) occurred signifi- tients. Large population-based studies indicated that thecantly more in the endovascular-treated group (CAS 14% vs prevalence of carotid stenosis increases to 10% in personsCEA 4%). The incidence of recurrent ipsilateral stroke ap- 80 years old [69]. In a subgroup analysis of NASCET, thepeared to be higher in the first year in cases of stenoses benefits of CEA in patients 75 years with symptomaticoccurring after CAS compared with stenoses occurring after carotid stenosis was compared with the benefit seen inCEA. However, survival analysis at 3-year follow-up younger patients [70]. Among medically treated patients,showed no difference in the occurrence of ipsilateral stroke the highest risk of stroke at 2 years was in patients 75(14.2%) between both groups [27,68]. The investigators years (36.5%). The perioperative rate of stroke and/or deathconcluded that there was a similar major risk and effective- was not higher in patients 75 years (5.2%) compared withness with endovascular treatment of ICA stenosis compared patients 65 years (7.9%). The absolute risk reduction bywith CEA, but minor complications were avoided with CEA in patients 75 years was 28.9% (number needed toendovascular treatment. Notably, the wide 95% confidence treat 3% of patients). The ECST data also indicate thatintervals in this study for stroke rate make interpretation of increasing age is associated with greater benefit from CEAthe data even harder. Results were certainly not up to the in patients with symptomatic carotid stenosis [71]. Further-standard advocated by the American Heart Association. more, Miller et al [72] showed, in a prospective analysis of The Kentucky randomized trials comparing CAS with 300 CEAs performed in patients 80 years, that periop-CEA were published in 2001 and 2004. The first publication erative risk is increased, but outcomes remain within ac-focused on symptomatic patients; the latter focused on ceptable guidelines [72].asymptomatic patients. Both studies reported low compli- In the Stenting and Angioplasty With Protection in Pa-cation rates for either treatment and challenged the “gold tients at High Risk for Endarterectomy (SAPPHIRE) trial,standard” of CEA [22,23]. However, the small number of the hypothesis was that CAS was not inferior to CEA inpatients in each group makes the extraordinarily low risk high-risk patients [29]. Both surgeons and interventionalrate difficult to interpret. Afterward, interest shifted to those cardiologists had to meet certain procedural criteria to par-patients who might benefit most from CAS. ticipate. Surgeons were required to have performed an av-
  • 6. 264 M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269erage of 30 CEAs/y, with low corresponding major com- Recent publicationsplication (eg, death, stroke, and/or myocardial infarction) Recently, results of 2 independent randomized noninfe-rates of 1%. The interventionalists were required to have riority controlled trials, the Stent-Protected Angioplastyperformed an average of 64 interventions/y, with low cor- versus Carotid Endarterectomy (SPACE) trial and the End-responding complication (eg, stroke, TIA) rates of 2%. A arterectomy Versus Stenting in Patients with Symptomatictotal of 723 symptomatic (stenosis 50%) or asymptomatic Severe Carotid Stenosis (EVA-3S) trial, were published(stenosis 80%) patients–normally deemed high risk for (Table 3). The SPACE trial included 1,183 symptomaticsurgery because of concomitant morbidity, such as cardio- patients with a 70% stenosis of the ICA [25]. Patientspulmonary disease or previous surgery–were considered were randomly allocated to either CAS or CEA. The tech-suitable for entry to either the endovascular- or surgical- nique used by the interventional physician (ie, type of stent,treatment arms. Consensus agreement by a multidisciplin- whether or not to use a protection device) was not restrictedary team of neurologists, surgeons, and interventionalists by protocol. Primary outcome was ipsilateral stroke, withwas required for a patient’s enrollment into the randomized symptoms lasting 24 hours or death between randomisa- tion and 30 days after treatment. The complication rate at 30arm of study. EPDs were used in the endovascular-treated days was 6.8% for CAS versus 6.3% for CEA. The nonin-group. The primary end point was the cumulative incidence feriority test was not significant (P .09). In this study, theof major cardiovascular events at 30 days and at 1 year after investigators concluded that CEA remains the preferredintervention. The study was stopped prematurely because of treatment for patients with symptomatic ICA stenosis be-slow enrollment: Most patients initially included were fi- cause evidence is lacking for equivalent or superior endo-nally excluded because perioperative risk with CEA was vascular treatment.deemed too high (n 409). Finally, 317 patients were The EVA-3S trial included 527 symptomatic patientsrandomized to CEA or CAS. Among patients in the ran- with an ICA stenosis of 60% to 90% according to NASCETdomized study, a significantly higher number of patients in guidelines [26]. The primary end point was any stroke orthe stenting arm had undergone previous coronary artery death within 30 days after intervention. The systematic usebypass (CAS 43% vs CEA 31%, P 0.05) and also had of a CPD was instituted during the trial on instigation of thehigher history of cardiovascular disease (CAS 85% vs CEA safety committee. Analysis showed a significant higher risk74%, P .05). for death or any stroke at 30 days for endovascular treat- The 30-day myocardial infarction, stroke, and death rate ment (9.6%) compared with CEA (3.9%), with a relativewas 4.8% in the CAS arm versus 9.8% in the CEA arm, thus risk of 2.5% and an absolute risk of 5.7%. Although morefavoring endovascular treatment (P .09) [29]. Results at minor and systemic complications occurred after CEA, this1 year (eg, myocardial infarction, ipsilateral stroke, and/or did not reach significance, except for patients with cranialdeath) were also in favor of endovascular treatment: 12.2% nerve injury. Noteworthy, the trial was ended prematurelyversus 20.1% for patients treated by surgery (P .048). for safety reasons. Inclusion stopped after enrollment of 527The 3-year incidence of stroke was similar between both patients, although power analysis indicated that 872 patientsarms (7%). were needed to reach a statistical power of 80%. Because Importantly, differences in this trial between CAS and the study was ended prematurely, the inferiority questionCEA treatment at the composite 1-year end point were still remains. Nevertheless, the results of CAS in therelated to a greater association of CEA with myocardial EVA-3s study differed from those in the SAPPHIRE trial.infarction. Without the inclusion of myocardial infarction, Reasons are probably multifactorial and may have been theno statistical differences in rates of stroke and/or death inclusion of more symptomatic patients in the EVA-3sbetween both groups would have been noted (CAS 5.5% vs study, the use of a protection device and antiplatelet ther-CEA 8.4%, P .4). The majority of myocardial infarctions apy, the EVA-3s study patients not being at high risk ofwere non–Q-wave events identified by routine postproce- developing coronary artery disease, and varying levels ofdural laboratory studies. experience in performing CAS. Furthermore, a systematic review showed that the 30-day rate of death or stroke after The majority of patients in the SAPPHIRE trial were CAS was 5.8% among patients treated without EPD com-asymptomatic. In the CAS arm, only 30% of patients were pared with 1.8% among those treated with EPD [58]. Earlysymptomatic; in the CEA arm, only 28% were symptomatic. in the EVA-3S trial, EPDs were not used, and the incidenceThe primary end point did not differ in these symptomatic of stroke was 25%. The study was even briefly stoppedpatients. In asymptomatic patients there was a difference and later on restarted with the incorporation of routine useafter one year in favor for those treated with CAS. of cerebral-protection devices. Nevertheless, the incidence A Cochrane review published in 2005 showed only 5 of stroke remained higher compared with CEA. Furtherrandomized controlled trials comparing CAS with CEA evidence must be awaited from a meta-analysis, which has[28]. The combined primary outcomes, defined as any been planned from the combined results after completion ofstroke or death within 30 days of intervention, did not differ the SPACE and EVA-3S trials and the still-ongoing Inter-between treatment arms. The meta-analysis was limited by national Carotid Stenting Study [73].the premature ending of 3 trials because of inconsistent useof stents and EPDs and heterogeneity of groups with regardto symptomatic status and surgical risk. Because of these The High-Risk Patientlimitations, this review concluded that CEA remained the Some conclude that CAS may be an excellent procedure“gold standard” of treatment. for high-risk patients who are not fit for surgery. Is CEA per
  • 7. M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269 265se harmful in high-risk patients? It seems that when patients vincingly proven that CEA significantly decreases the riskmeet NASCET or ACAS exclusion criteria, they are marked of subsequent stroke in patients with severe carotid “high-risk.” However, complication rates in these high- Currently, surgery remains the “golden standard” of treat-risk patients are not per se increased when performing CEA. ment, but CAS has progressed in recent years and chal-Mozes [74] and Mozes et al [75] analyzed their CEA results lenged CEA. Despite many trials, only a few methodolog-by stratifying according to SAPPHIRE criteria for high-risk ically correct randomized trials compared CAS with CEA,patients [74,75]. Such criteria included positive stress test, and they failed to establish consensus. Using predefinedage 80 years, contralateral carotid occlusion, and repeated margins of noninferiority, recent trials–such as the SPACECEA. There were no statistical differences in either stroke and EVA-3S trials–indicated that CAS is not as good asor death rate between low- and high-risk patients. The CEA. Proponents of CAS responded by focusing on theinvestigators showed that CEA can be performed in such “interventionists’ experience and CAS methods” in bothhigh-risk patients with acceptable standard complication trials. Consequently, many have been left questioning therates. Ballotta et al [76] and Nguyen et al [77] showed that future of CAS compared with CEA.high-risk patients are more common than previously It is important to realize that most randomized trialsthought. Their perioperative neurologic and cardiac out- comparing CEA with CAS did not succeed in achievingcomes are comparable with those reported in other pa- recruitment as determined before the study. The Leicester,tients [76,77]. The idea that operative risk is higher in WALLSTENT, SPACE, and EVA-3S trials specified thatpatients excluded from NASCET or ACAS has not been the total intended number of patients should be 3,772. How-not supported. Definite accepted criteria to identify high- ever, only a total of 1,989 patients (52%) were randomizedrisk patients have not yet been developed. A study from as a result of early trial completion because of excess in riskthe Cleveland Clinic attempted by retrospective analysis in the CAS arm. The expanded use of CAS outside orga-to identify a subgroup of patients who were at increased nized randomized clinical trials further threatens studies ofrisk for CEA. From a prospective database covering a alternatives to CEA.10-year period, 3,061 patients with histories of CEA were Failure to achieve a study or meta-analysis with adequateexamined. High-risk patients were identified on the basis size will not produce convincing evidence of the value ofof presence of coronary artery disease, congestive heart CAS in stroke prevention. An important reason thatfailure, severe chronic obstructive disease, or renal fail- NASCET, ECST, ACST, and ACAS influenced clinicalure. The composite risk for stroke, death, and myocardial practice and proved the importance of CEA is that theyinfarction was 7.4% in high-risk patients compared with included large numbers of patients. It is therefore important3.8% in others. Perhaps such patients would benefit from to limit the use of CAS to randomized trials to ensurealternatives to CEA. statistical power to produce a consensus in best evidence- The above-mentioned risk factors, (ie, degree of stenosis, based therapy in patients with severe carotid stenosis.neurologic symptoms, etc) do not sufficiently identify the The technical expertise required from interventionistsreal risk presented by the patient. In contrast, plaque mor- participating in trials comparing CAS with CEA may in partphology may identify patients at risk for stroke during explain the excessive risk of CAS procedures. The require-intervention [78 – 82]. The risk of rupture is strongly related ments stipulated for interventionists in the EVA-3S trialto plaque composition and degree of carotid stenosis were having performed 12 previous CAS or 35 previous[80,83,84]. Gray-scale measurements (GSM) of intima– supra-aortic stenting procedures, and interventionists whomedia thickness using ultrasound have been studied to an- had not met these requirements still were allowed to partic-alyze vulnerable plaques. GSM is an overall measure of ipate in the study when their CAS procedures were super-plaque echogenicity in which low-GSM plaques generate vised. Furthermore, CEA has evolved during the last 30more embolic particles [85]. The Imaging in Carotid An- years and has been widely used by experienced vasculargioplasty and Risk of Stroke study showed that the onset of surgeons. In contrast, CAS is still in development and mayneurologic deficits during and after intervention signifi- not so easily be generalized. It is important to realize thatcantly increased in patients with low GSM values [86]. A the EVA-3S trial demonstrated what happens if CAS islow GSM is not a contraindication to CAS but rather a widely implemented by showing the results achieved whenpredictor of increased stroke risk. Low GSM values are CAS is performed outside of the “top” CAS units. Again,further related to future coronary events, higher rate of this calls for exclusive performance of CAS procedures inrestenosis, positive brain computed axial tomography for controlled clinical trials using standards of practice andischemic lesions, and rapid plaque progression [87–91]. expert technical skills.Other modalities, such as high-resolution magnetic reso- Some have concluded that CAS may be an excellentnance imaging, have also been tested as measures of plaque procedure for high-risk patients who are not fit for surgery.composition [92–97]. These imaging techniques may be- However, both CAS and CEA are being compared with thecome important in the planning of future clinical trials and BMT of more than a decade ago. Notably, the cumulativeBMT modalities. complication risk in SAPPHIRE is striking: 17% after 3 years for both CAS and CEA. As pointed out by others, perhaps such high-risk patients are better off without stent-Comments ing or endarterectomy [77]. Medical treatment has evolved The longevity of CEA predominantly has been deter- with modern angiotensin-converting enzymes inhibitors,mined by comparison among large-scale randomized trials. other antihypertensive drugs, statin medications, and newerRandomized trials comparing CEA with BMT have con- antiplatelet therapies [98 –102]. In the NASCET trial, only
  • 8. 266 M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –26950% of patients with increased lipid levels received lipid- provides better stroke prevention compared with CEA.lowering medication. A recent meta-analysis analyzing the Therefore, CEA still remains the “gold standard” of treat-relationship between statins and the risk of stroke showed a ment. Furthermore, evolving BMT, timely intervention, andrelative stroke reduction rate 21% [103]. The anti-inflam- analysis of plaque composition may have an important in-matory effects of statins seem as important as their lipid- fluence on the future treatment of patients with carotidlowering effects [104,105]. For antithrombotic therapy, artery stenosis.most patients in the NASCET and ACAS trials were takingaspirin only. In a large study, clopidogrel was comparedwith aspirin, and clopidogrel conferred an 8.7% risk reduc- References [1] Moore WS, Barnett HJ, Beebe HG, et al. Guidelines for carotidtion for the prevention of stroke and an even greater reduc- endarterectomy. A multidisciplinary consensus statement from thetion in high-risk patients [106,107]. Increased levels of Ad Hoc Committee, American Heart Association. Circulation 1995;homocysteine have also been associated with increased 91:566 –79.stroke risk, and lower homocysteine levels have been re- [2] Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics–2007 update: a report from the American Heart Associa-lated to a lower risk of cardiovascular restenosis [108 –110]. tion Statistics Committee and Stroke Statistics Subcommittee. Cir-However, high levels of homocysteine seem not to increase culation 2007;115:e69 – e71.the risk of restenosis after CEA [111,112]. Finally, the use [3] Ghatnekar O, Persson U, Glader EL, et al. Cost of stroke inof angiotensin-converting enzyme inhibitors also decreases Sweden: an incidence estimate. Int J Technol Assess Health Carestroke risk, as demonstrated by the Heart Outcome Preven- 2004;375– 80. [4] Kolominsky-Rabas PL, Heuschmann PU, Marschall D, et al. Life-tion Evaluation Study [113]. In this study, patients not time cost of ischemic stroke in Germany: results and national pro-known to have low ventricular ejection fraction or heart jections from a population-based stroke registry: the Erlangenfailure derived benefit from using ramipril, not only for Stroke Project. Stroke 2006;37:1179 – 83.coronary events but also for ischemic strokes. [5] Meyers PM, Schumacher HC, Higashida RT, et al. Use of stents to treat extracranial cerebrovascular disease. Annu Rev Med 2006;57: In contrast, one should consider patient commitment, pa- 437–54.tient potential to receive lesser therapy due to randomization, [6] Sauerbeck LR. Primary stroke prevention. Am J Nurs 2006;106:and cost when advocating repetition of previous trials. Further- 40 – 8.more, despite the proven efficacy of BMT, it is important to [7] Weinberger J. Prevention of ischemic stroke. Curr Treat Optionsrealize that only a small number of patients actually take their Cardiovasc Med 2002;4:393– 403. [8] Weinberger J. Stroke and TIA. Prevention and management ofdrugs; it takes sometimes several years of treatment before cerebrovascular events in primary care. Geriatrics 2002;57:38 – 43.benefit in risk reduction is reached; and the mentioned risk [9] Hemphill JC III. Ischemic stroke. Clinical strategies based on mech-reductions are sometimes “misleading” [114 –117]. Fortu- anisms and risk factors. Geriatrics 2000;55:42–52.nately, a new study–Transatlantic Asymptomatic Carotid In- [10] Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council of the American Heart Associa-tervention Trial, a randomized trial–is currently comparing tion. Guidelines for the management of transient ischemic attacks.CEA, CAS, and current BMT [118]. Stroke 1994;25:1320 –35. Time to surgery after the first event in carotid stenosis is [11] Moore WS. The American Heart Association Consensus Statementanother important aspect to consider when comparing the on guidelines for carotid endarterectomy. Semin Vasc Surg 1995;8:results and effectiveness of different interventions. Delay- 77– 81. [12] Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention ofing surgery in patients with symptomatic carotid stenosis ischemic stroke: a guideline from the American Heart Association/significantly decreases the aimed-for long-term stroke re- American Stroke Association Stroke Council: cosponsored by theduction [119 –121]. Delaying CEA for 12 weeks almost Atherosclerotic Peripheral Vascular Disease Interdisciplinary Work-decreased a positive effect on stroke prevention in the long- ing Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; andterm, still putting these patients at risk for perioperative the Quality of Care and Outcomes Research Interdisciplinary Work-complications [15]. Unfortunately, systematic delay in sur- ing Group. Circulation 2006;113:e873– e923.gery 12 weeks seems currently to be the common practice [13] Randomised trial of endarterectomy for recently symptomatic ca-[120]. A recent population based study in the United King- rotid stenosis: final results of the MRC European Carotid Surgerydom showed that only 43% of symptomatic patients with Trial (ECST). Lancet 1998;351:1379 – 87. [14] North American Symptomatic Carotid Endarterectomy Trial Col-severe carotid stenosis and who had a stroke risk before laborators. Beneficial effect of carotid endarterectomy in symptom-CEA of 32% at week 12 underwent surgery at 12 weeks atic patients with high-grade carotid stenosis. N Engl J Med 1991;[120]. The highest risk of stroke in the first weeks after the 325:445–53.primary event may be related to plaque vulnerability and/or [15] Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy formorphology. Plaque in the early period has been character- symptomatic carotid stenosis. Lancet 2003;361:107–16.ized by thrombosis formation and spontaneous embolization [16] Ederle J, Brown MM. The evidence for medicine versus surgery for[122–124]. Classical opinions in CEA have been that early carotid stenosis. Eur J Radiol 2006;60:3– is associated with increased perioperative risk. Nev- [17] Moore WS. Resolved: NASCET and ACAS need not be repeated:ertheless, delaying surgery may seem to decrease perioper- the affirmative position. Arch Neurol 2003;60:775– 8. [18] Mullenix PS, Tollefson DF, Olsen SB, et al. Intraoperative duplexative risk but at the expense of long-term benefits: Delaying ultrasonography as an adjunct to technical excellence in 100 con-CEA can be accompanied by stroke risks up to 20% at 4 secutive carotid endarterectomies. Am J Surg 2003;185:445–9.weeks [120,125]. Overall, many patients may benefit from [19] Bettendorf MJ, Mansour MA, Davis AT, et al. Carotid angioplastyfast-track CEA regarding prevention of stroke. and stenting versus redo endarterectomy for recurrent stenosis. Am J Surg 2007;193:356 –9. In conclusion, CAS performed with embolic EPDs can [20] Satler LF, Hoffmann R, Lansky A, et al. Carotid stent-assistedbe an effective treatment for patients with carotid artery angioplasty: preliminary technique, angiography, and intravascularstenosis. However, presently there is no evidence that CAS ultrasound observations. J Invasive Cardiol 1996;8:23–30.
  • 9. M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269 267[21] Naylor AR, Bolia A, Abbott RJ, et al. Randomized study of carotid [43] Theron J. Protected carotid angioplasty and carotid stents. J Mal angioplasty and stenting versus carotid endarterectomy: a stopped Vasc 1996;21(suppl A):113–22. trial. J Vasc Surg 1998;28:326 –34. [44] Wholey MH, Wholey MH, Jarmolowski CR, et al. Endovascular[22] Brooks WH, McClure RR, Jones MR, et al. Carotid angioplasty and stents for carotid artery occlusive disease. J Endovasc Surg 1997;4: stenting versus carotid endarterectomy: randomized trial in a com- 326 –38. munity hospital. J Am Coll Cardiol 2001;38:1589 –95. [45] Kachel R. Results of balloon angioplasty in the carotid arteries. J[23] Brooks WH, McClure RR, Jones MR, et al. Carotid angioplasty and Endovasc Surg 1996;3:22–30. stenting versus carotid endarterectomy for treatment of asymptom- [46] Diethrich EB, Ndiaye M, Reid DB. Stenting in the carotid artery: atic carotid stenosis: a randomized trial in a community hospital. initial experience in 110 patients. J Endovasc Surg 1996;3:42– 62. Neurosurgery 2004;54:318 –24. [47] Yadav JS, Roubin GS, Iyer S, et al. Elective stenting of the extracra-[24] Hobson RW, Howard VJ, Roubin GS, et al. Carotid artery stenting nial carotid arteries. Circulation 1997;95:376 – 81. is associated with increased complications in octogenarians: 30-day [48] Criado FJ, Wellons E, Clark NS. Evolving indications for and early stroke and death rates in the CREST lead-in phase. J Vasc Surg results of carotid artery stenting. Am J Surg 1997;174:111– 4. 2004;40:1106 –11. [49] Bergeron P, Roux M, Khanoyan P, et al. Long-term results of[25] Ringleb PA, Allenberg J, Bruckmann H, et al. 30 day results from carotid stenting are competitive with surgery. J Vasc Surg 2005;41: the SPACE trial of stent-protected angioplasty versus carotid end- 213–21. arterectomy in symptomatic patients: a randomised non-inferiority [50] Roubin GS, New G, Iyer SS, et al. Immediate and late clinical trial. Lancet 2006;368:1239 – 47. outcomes of carotid artery stenting in patients with symptomatic and[26] Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus asymptomatic carotid artery stenosis: a 5-year prospective analysis. stenting in patients with symptomatic severe carotid stenosis. N Engl Circulation 2001;103:532–7. J Med 2006;355:1660 –71. [51] Henry M, Amor M, Masson I, et al. Angioplasty and stenting of the[27] Endovascular versus surgical treatment in patients with carotid ste- extracranial carotid arteries. J Endovasc Surg 1998;5:293–304. nosis in the Carotid and Vertebral Artery Transluminal Angioplasty [52] Teitelbaum GP, Lefkowitz MA, Giannotta SL. Carotid angioplasty Study (CAVATAS): a randomised trial. Lancet 2001;357:1729 –37. and stenting in high-risk patients. Surg Neurol 1998;50:300 –11.[28] Coward LJ, Featherstone RL, Brown MM. Safety and efficacy of [53] Jordan Jr WD, Voellinger DC, Doblar DD, et al. Microemboli endovascular treatment of carotid artery stenosis compared with detected by transcranial Doppler monitoring in patients during ca- carotid endarterectomy: a Cochrane systematic review of the ran- rotid angioplasty versus carotid endarterectomy. Cardiovasc Surg domized evidence. Stroke 2005;36:905–11. 1999;7:33– 8.[29] Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery [54] Crawley F, Clifton A, Buckenham T, et al. Comparison of hemo- stenting versus endarterectomy in high-risk patients. N Engl J Med dynamic cerebral ischemia and microembolic signals detected dur- 2004;351:1493–501. ing carotid endarterectomy and carotid angioplasty. Stroke 1997;28:[30] Debakey ME. Carotid endarterectomy revisited. J Endovasc Surg 2460 – 4. 1996;3:4. [55] Stockx L. Techniques in carotid artery stenting. Eur J Radiol 2006;[31] Debakey ME. Successful carotid endarterectomy for cerebrovascular 60:11–3. insufficiency. Nineteen-year follow-up. JAMA 1975;233:1083–5. [56] Macdonald S. The evidence for cerebral protection: an analysis and[32] Mayberg MR, Wilson SE, Yatsu F, et al. Carotid endarterectomy summary of the literature. Eur J Radiol 2006;60:20 –5. and prevention of cerebral ischemia in symptomatic carotid stenosis. [57] Wholey MH, Al Mubarek N, Wholey MH. Updated review of the Veterans Affairs Cooperative Studies Program 309 Trialist Group. global carotid artery stent registry. Catheter Cardiovasc Interv 2003; JAMA 1991;266:3289 –94. 60:259 – 66.[33] Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid end- [58] Kastrup A, Groschel K, Krapf H, et al. Early outcome of carotid arterectomy in patients with symptomatic moderate or severe steno- angioplasty and stenting with and without cerebral protection de- sis. North American Symptomatic Carotid Endarterectomy Trial vices: a systematic review of the literature. Stroke 2003;34:813–9. Collaborators. N Engl J Med 1998;339:1415–25. [59] Fanelli F, Bezzi M, Boatta E, et al. Techniques in cerebral protec-[34] Fox AJ, Eliasziw M, Rothwell PM, et al. Identification, prognosis, tion. Eur J Radiol 2006;60:26 –36. and management of patients with carotid artery near occlusion. [60] Vitek JJ, Roubin GS, Al Mubarek N, et al. Carotid artery stenting: AJNR Am J Neuroradiol 2005;26:2086 –94. technical considerations. AJNR Am J Neuroradiol 2000;21:1736 – 43.[35] Endarterectomy for asymptomatic carotid artery stenosis. Executive [61] White CJ, Iyer SS, Hopkins LN, et al. Carotid stenting with distal Committee for the Asymptomatic Carotid Atherosclerosis Study. protection in high surgical risk patients: the BEACH trial 30 day JAMA 1995;273:1421– 8. results. Catheter Cardiovasc Interv 2006;67:503–12.[36] Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and [62] Safian RD, Bacharach JM, Ansel GM, et al. Carotid stenting with a fatal strokes by successful carotid endarterectomy in patients with- new system for distal embolic protection and stenting in high-risk out recent neurological symptoms: randomised controlled trial. Lan- patients: the carotid revascularization with ev3 arterial technology cet 2004;363:1491–502. evolution (CREATE) feasibility trial. Catheter Cardiovasc Interv[37] Taylor DW, Barnett HJ, Haynes RB, et al. Low-dose and high-dose 2004;63:1– 6. acetylsalicylic acid for patients undergoing carotid endarterectomy: [63] Gray WA, Hopkins LN, Yadav S, et al. Protected carotid stenting in a randomised controlled trial. ASA and Carotid Endarterectomy high-surgical-risk patients: the ARCHeR results. J Vasc Surg 2006; (ACE) Trial Collaborators. Lancet 1999;353:2179 – 84. 44:258 – 68.[38] Cronenwett JL, Birkmeyer JD, Nackman GB, et al. Cost-effective- [64] Gonzalez A, Gonzalez-Marcos JR, Martinez E, et al. Safety and ness of carotid endarterectomy in asymptomatic patients. J Vasc security of carotid artery stenting for severe stenosis with contralat- Surg 1997;25:298 –309. eral occlusion. Cerebrovasc Dis 2005;20(suppl 2):123– 8.[39] Kuntz KM, Kent KC. Is carotid endarterectomy cost-effective? An [65] Gray WA, Yadav JS, Verta P, et al. The CAPTURE registry: results analysis of symptomatic and asymptomatic patients. Circulation of carotid stenting with embolic protection in the post approval 1996;94:II194 –II198. setting. Catheter Cardiovasc Interv 2006;69:341– 8.[40] Moore WS, Barnett HJ, Beebe HG, et al. Guidelines for carotid [66] CaRESS Steering Committee. Carotid Revascularization Using endarterectomy. A multidisciplinary consensus statement from the Endarterectomy or Stenting Systems (CaRESS) phase I clinical trial: ad hoc Committee, American Heart Association. Stroke 1995;26: 1-year results. J Vasc Surg 2005;42:213–9. 188 –201. [67] Dudek D, Bartus S, Rakowski T, et al. MO.MA–a new cerebral[41] Bockenheimer SA, Mathias K. Percutaneous transluminal angio- stroke protection system during carotid artery stenting. Kardiol Pol plasty in arteriosclerotic internal carotid artery stenosis. AJNR Am J 2005;62:559 –70. Neuroradiol 1983;4:791–2. [68] McCabe DJ, Pereira AC, Clifton A, et al. Restenosis after carotid[42] Courtheoux P, Theron J, Tournade A, et al. Percutaneous endolu- angioplasty, stenting, or endarterectomy in the Carotid and Vertebral minal angioplasty of post endarterectomy carotid stenoses. Neuro- Artery Transluminal Angioplasty Study (CAVATAS). Stroke 2005; radiology 1987;29:186 –9. 36:281– 6.
  • 10. 268 M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269 [69] Prati P, Vanuzzo D, Casaroli M, et al. Determinants of carotid [91] Setacci C, de Donato G, Setacci F, et al. In-stent restenosis after plaque occurrence. A long-term prospective population study: the carotid angioplasty and stenting: a challenge for the vascular sur- San Daniele Project. Cerebrovasc Dis 2006;22:416 –22. geon. Eur J Vasc Endovasc Surg 2005;29:601–7. [70] Alamowitch S, Eliasziw M, Algra A, et al. Risk, causes, and pre- [92] Touze E, Toussaint JF, Coste J, et al. Reproducibility of high- vention of ischaemic stroke in elderly patients with symptomatic resolution MRI for the identification and the quantification of carotid internal-carotid-artery stenosis. Lancet 2001;357:1154 – 60. atherosclerotic plaque components. Consequences for prognosis [71] Rothwell PM, Warlow CP. Prediction of benefit from carotid end- studies and therapeutic trials. Stroke 2007;38:1812–9. arterectomy in individual patients: a risk-modelling study. European [93] Liu F, Xu D, Ferguson MS, Chu B, et al. Automated in vivo Carotid Surgery Trialists’ Collaborative Group. Lancet 1999;353: segmentation of carotid plaque MRI with morphology-enhanced 2105–10. probability maps. Magn Reson Med 2006;55:659 – 68. [72] Miller MT, Comerota AJ, Tzilinis A, et al. Carotid endarterectomy [94] Wolf RL, Wehrli SL, Popescu AM, et al. Mineral volume and in octogenarians: does increased age indicate “high risk”? J Vasc morphology in carotid plaque specimens using high-resolution MRI Surg 2005;41:231–7. and CT. Arterioscler Thromb Vasc Biol 2005;25:1729 –35. [73] Featherstone RL, Brown MM, Coward LJ. International carotid [95] Luo Y, Polissar N, Han C, et al. Accuracy and uniqueness of three stenting study: protocol for a randomised clinical trial comparing in vivo measurements of atherosclerotic carotid plaque morphology carotid stenting with endarterectomy in symptomatic carotid artery with black blood MRI. Magn Reson Med 2003;50:75– 82. stenosis. Cerebrovasc Dis 2004;18:69 –74. [96] Estes JM, Quist WC, Lo Gerfo FW, et al. Noninvasive character- [74] Mozes G, Sullivan TM, Torres-Russotto DR, et al. Carotid endar- ization of plaque morphology using helical computed tomography. terectomy in SAPPHIRE-eligible high-risk patients: implications for J Cardiovasc Surg (Torino) 1998;39:527–34. selecting patients for carotid angioplasty and stenting. J Vasc Surg [97] Gronholdt ML, Wagner A, Wiebe BM, et al. Spiral computed 2004;39:958 – 65. tomographic imaging related to computerized ultrasonographic im- [75] Mozes G. High-risk carotid endarterectomy. Semin Vasc Surg 2005; ages of carotid plaque morphology and histology. J Ultrasound Med 18:61– 8. 2001;20:451– 8. [76] Ballotta E, Da Giau G, Baracchini C, et al. Carotid endarterectomy [98] Adams Jr HP, del Zoppo G, Alberts MJ, et al. Guidelines for the in high-risk patients: a challenge for endovascular procedure proto- early management of adults with ischemic stroke: a guideline from cols. Surgery 2004;135:74 – 80. the American Heart Association/American Stroke Association [77] Nguyen LL, Conte MS, Reed AB, et al. Carotid endarterectomy: Stroke Council, Clinical Cardiology Council, Cardiovascular Radi- who is the high-risk patient? Semin Vasc Surg 2004;17:219 –23. ology and Intervention Council, and the Atherosclerotic Peripheral [78] Verhoeven B, Hellings WE, Moll FL, et al. Carotid atherosclerotic Vascular Disease and Quality of Care Outcomes in Research Inter- plaques in patients with transient ischemic attacks and stroke have disciplinary Working Groups: the American Academy of Neurology unstable characteristics compared with plaques in asymptomatic and affirms the value of this guideline as an educational tool for neurol- amaurosis fugax patients. J Vasc Surg 2005;42:1075– 81. ogists. Stroke 2007;38:1655–711. [79] Trivedi RA, King-Im JM, Graves MJ, et al. Non-stenotic ruptured [99] Touze E, Mas JL, Rother J, et al. Impact of carotid endarterectomy atherosclerotic plaque causing thrombo-embolic stroke. Cerebro- on medical secondary prevention after a stroke or a transient isch- vasc Dis 2005;20:53–5. emic attack: results from the Reduction of Atherothrombosis for [80] McCarthy MJ, Loftus IM, Thompson MM, et al. Angiogenesis and Continued Health (REACH) registry. Stroke 2006;37:2880 –5. the atherosclerotic carotid plaque: an association between symptom- [100] Frawley JE, Hicks RG, Woodforth IJ. Risk factors for peri-operative atology and plaque morphology. J Vasc Surg 1999;30:261– 8. stroke complicating carotid endarterectomy: selective analysis of a [81] Carr SC, Farb A, Pearce WH, et al. Activated inflammatory cells are prospective audit of 1000 consecutive operations. Aust N Z J Surg associated with plaque rupture in carotid artery stenosis. Surgery 2000;70:52– 6. 1997;122:757– 63. [101] Somerfield J, Barber PA, Anderson NE, et al. Changing attitudes to [82] Balzer K, Boesger U, Muller KM. Plaque morphology of the carotid bifurcation and incidence of embolisms in relation clinical stage of the management of ischaemic stroke between 1997 and 2004: a cerebrovascular insufficiency. Kongressbd Dtsch Ges Chir Kongr survey of New Zealand physicians. Intern Med J 2006;36:276 – 80. 2002;119:631– 4. [102] Idris I, Thomson GA, Sharma JC. Diabetes mellitus and stroke. Int [83] Fisher M, Paganini-Hill A, Martin A, et al. Carotid plaque pathol- J Clin Pract 2006;60:48 –56. ogy: thrombosis, ulceration, and stroke pathogenesis. Stroke 2005; [103] Amarenco P, Labreuche J, Lavallee P, et al. Statins in stroke pre- 36:253–7. vention and carotid atherosclerosis: systematic review and up-to- [84] Rothwell PM, Gibson R, Warlow CP, on behalf of the European date meta-analysis. Stroke 2004;35:2902–9. Carotid Surgery Trialists’ Collaborative Group. Interrelation be- [104] Davignon J. Beneficial cardiovascular pleiotropic effects of statins. tween plaque surface morphology and degree of stenosis on carotid Circulation 2004;109:III39 –III43. angiograms and the risk of ischemic stroke in patients with symp- [105] Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity tomatic carotid stenosis. Stroke 2000;31:615–21. statin therapy on regression of coronary atherosclerosis: the [85] Ackerstaff RG, Jansen C, Moll FL, et al. The significance of mi- ASTEROID trial. JAMA 2006;295:1556 – 65. croemboli detection by means of transcranial Doppler ultrasonog- [106] CAPRIE Steering Committee. A randomised, blinded, trial of clo- raphy monitoring in carotid endarterectomy. J Vasc Surg 1995;21: pidogrel versus aspirin in patients at risk of ischaemic events 963–9. (CAPRIE). Lancet 1996;348:1329 –39. [86] Biasi GM, Froio A, Diethrich EB, et al. Carotid plaque echolucency [107] Bhatt DL, Chew DP, Hirsch AT, et al. Superiority of clopidogrel increases the risk of stroke in carotid stenting: the Imaging in versus aspirin in patients with prior cardiac surgery. Circulation Carotid Angioplasty and Risk of Stroke (ICAROS) study. Circula- 2001;103:363– 8. tion 2004;110:756 – 62. [108] Hankey GJ. Secondary prevention of recurrent stroke. Stroke 2005; [87] Flach HZ, Ouhlous M, Hendriks JM, et al. Cerebral ischemia after 36:218 –21. carotid intervention. J Endovasc Ther 2004;11:251–7. [109] Smith TP, Cruz CP, Brown AT, et al. Folate supplementation in- [88] Wolf O, Heider P, Heinz M, et al. Microembolic signals detected by hibits intimal hyperplasia induced by a high-homocysteine diet in a transcranial Doppler sonography during carotid endarterectomy and rat carotid endarterectomy model. J Vasc Surg 2001;34:474 – 81. correlation with serial diffusion-weighted imaging. Stroke 2004;35: [110] Southern F, Eidt J, Drouilhet J, et al. Increasing levels of dietary e373– e375. homocystine with carotid endarterectomy produced proportionate [89] Johnsen SH, Mathiesen EB, Fosse E, et al. Elevated high-density increases in plasma homocysteine and intimal hyperplasia. Athero- lipoprotein cholesterol levels are protective against plaque progres- sclerosis 2001;158:129 –38. sion: a follow-up study of 1952 persons with carotid atherosclerosis: [111] Assadian A, Rotter R, Assadian O, et al. Homocysteine and early the Tromso study. Circulation 2005;112:498 –504. re-stenosis after carotid eversion endarterectomy. Eur J Vasc Endo- [90] Honda O, Sugiyama S, Kugiyama K, et al. Echolucent carotid vasc Surg 2006;33:144 – 8. plaques predict future coronary events in patients with coronary [112] Samson RH, Yungst Z, Showalter DP. Homocysteine, a risk factor artery disease. J Am Coll Cardiol 2004;43:1177– 84. for carotid atherosclerosis, is not a risk factor for early recurrent
  • 11. M.G. van der Vaart et al. / The American Journal of Surgery 195 (2008) 259 –269 269 carotid stenosis following carotid endarterectomy. Vasc Endovasc [120] Fairhead JF, Mehta Z, Rothwell PM. Population-based study of Surg 2004;38:345– 8. delays in carotid imaging and surgery and the risk of recurrent[113] Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin- stroke. Neurology 2005;65:371–5. converting-enzyme inhibitor, ramipril, on cardiovascular events in [121] Johnston SC, Nguyen-Huynh MN, Schwarz ME, et al. National high-risk patients. The Heart Outcomes Prevention Evaluation Stroke Association guidelines for the management of transient isch- Study Investigators. N Engl J Med 2000;342:145–53. emic attacks. Ann Neurol 2006;60:301–13.[114] Hansson L. ‘Why don’t you do as I tell you?’ Compliance and [122] Molloy KJ, Thompson MM, Jones JL, et al. Unstable carotid antihypertensive regimens. Int J Clin Pract 2002;56:191– 6. plaques exhibit raised matrix metalloproteinase-8 activity. Circula-[115] Jones JK, Gorkin L, Lian JF, et al. Discontinuation of and changes tion 2004;110:337– 43. in treatment after start of new courses of antihypertensive drugs: a [123] Loftus IM, Naylor AR, Goodall S, et al. Increased matrix metallo- proteinase-9 activity in unstable carotid plaques. A potential role in study of a United Kingdom population. Br Med J 1995;311:293–5. acute plaque disruption. Stroke 2000;31:40 –7.[116] Hamilton-Craig I. The Heart Protection Study: implications for [124] Molloy KJ, Thompson MM, Schwalbe EC, et al. Elevation in clinical practice. The benefits of statin therapy do not come without plasma MMP-9 following carotid endarterectomy is associated with financial cost. Med J Aust 2002;177:407– 8. particulate cerebral embolisation. Eur J Vasc Endovasc Surg 2004;[117] Naylor AR. Does the modern concept of ‘best medical therapy’ 27:409 –13. render carotid surgery obsolete? Eur J Vasc Endovasc Surg 2004; [125] Baron EM, Baty DE, Loftus CM. The timing of carotid endarterec- 28:457– 61. tomy post stroke. Neurol Clin 2006;24:669 – 80.[118] Gaines PA, Randall MS. Carotid artery stenting for patients with [126] Waigand J, Gross CM, Uhlich F, et al. Elective stenting of carotid asymptomatic carotid disease (and news on TACIT). Eur J Vasc artery stenosis in patients with severe coronary artery disease. Eur Endovasc Surg 2005;30:461–3. Heart J 1998;19:1365–70.[119] Rothwell PM. Symptomatic and asymptomatic carotid stenosis: [127] Vozzi CR, Rodriguez AO, Paolantonio D, et al. Extracranial carotid how, when, and who to treat? Curr Atheroscler Rep 2006;8: angioplasty and stenting. Initial results and short-term follow-up. 290 –7. Tex Heart Inst J 1997;24:167–72.