Eur J Vasc Endovasc Surg (2011) 41, 717e719

EDITORIAL

Is Carotid Artery Stenting a Fair Alternative toCarotid Endarterectomy for Symptomatic CarotidArtery Stenosis?

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KEYWORDSSymptomatic carotidartery stenosis;Carotid endarterectomyt;Carotid artery stenting

78-5884/$36 ª 2011 European Societi:10.1016/j.ejvs.2011.03.018

In medicine, like politics, the ‘data’ or ‘facts’ can beinterpreted in more than one way. This interpretation or‘spin’ is often more important than anything else. Accordingto the recent guidelines by the American Heart Association/American Stroke Association (AHA/ASA) and several otherassociations, “carotid artery stenting (CAS) is indicated asan alternative to carotid endarterectomy (CEA) for symp-tomatic patients at average or low risk of complicationsassociated with endovascular intervention when the diam-eter of the lumen of the internal carotid artery is reduced bymore than 70% as documented by noninvasive imaging ormore than 50% as documented by catheter angiography andthe anticipated rate of periprocedural stroke or mortality isless than 6% (Class I; Level of Evidence B)”.1 The recentCarotid Revascularization Endarterectomy vs. Stenting Trial(CREST) results were used to support this recommendation.2

However, the facts leading to this recommendation mayhave more than one interpretation. This commentaryaddresses another possible interpretation.

Carotid artery stenting: an alternative forwhom?

According to Webster’s New World Dictionary, ‘alternative’is defined as “a choice between two things”.3 Thus, in theAHA/ASA recommendation, the word ‘alternative’ mayeasily be misinterpreted as ‘equivalent’ to justify thewidespread use of carotid artery stenting (CAS). Currentdata, however, indicate that CAS should be viewed neither

y for Vascular Surgery. Publishe

as an ‘alternative’ nor as an ‘equivalent’ treatment optionto carotid endarterectptomy (CEA) in the majority ofsymptomatic patients.

In CREST,2 there was no significant difference in theestimated 4-year rates of the composite primary end pointbetween CAS and CEA (7.2% vs. 6.8%, respectively; relativerisk (RR) 1.11; 95% confidence interval (CI) 0.81e1.51;p Z 0.51). The composite primary end point, however,consisted of stroke, myocardial infarction (MI) or deathfrom any cause.2 Although CAS was associated withconsiderably higher periprocedural stroke rates comparedwith CEA (4.1% vs. 2.3%, respectively; hazard ratio (HR)1.79; 95% CI 1.14e2.82; p Z 0.012), this was offset bya reduced risk of MI (1.1% vs. 2.3%, respectively;p Z 0.032).2 A recent subgroup analysis of CREST showedthat in symptomatic patients CAS was associated with analmost twofold increase in periprocedural stroke and deathrates compared with CEA (6.0% � 0.9% vs. 3.2% � 0.7%,respectively; HR 1.89; 95% CI 1.11e3.21; p Z 0.02).4

Therefore, CAS only showed equivalence of outcomeswith CEA when MIs were added to strokes. Quality-of-lifeindices, however, show that both major and minor strokesare likely to produce long-term physical limitations (withminor stroke associated with worse mental and physicalhealth at 1 year), whereas the effect of periprocedural MIon long-term physical and mental health is less.2,5

In addition to CREST, several other randomised studieshave demonstrated that in symptomatic patients CAS isassociated with higher rates of stroke,6�8 as well as

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Table 1 Randomized controlled trial (RCT) results showing higher rates of stroke/death and recurrent carotid stenosis afterCAS than CEA.

Study (year) Study design Study outcome

EVA-3S7

(2008)4-year data of EVA-3S Incidence of 30-day stroke/death rate: 15 of the 262 vs. 29 of the 265

patients, or 6.2% vs. 11.1%, for CEA vs. CAS, respectively (HR 1.97; 95%CI 1.06e3.67; p Z 0.03 for CAS vs. CEA).

SPACE9

(2008)2-year data of SPACE Incidence of ‡70% recurrent carotid stenosis: 10.7% vs. 4.6%, for CAS vs.

CEA, respectively; p Z 0.0009; or 11.1% vs. 4.6%, for CAS vs. CEA,respectively; p Z 0.0007, in the intention-to-treat and per-protocollife-table estimates, respectively.

Steinbaueret al. 8

(2009)

Single-center RCT comparing thelong-term results (66 � 14.2 vs..64 � 12.1 months, respectively) ofCAS (n Z 43) with CEA (n Z 44)

Patients undergoing CAS had higher rates of ipsilateral stroke(4 of 42 vs. 0 of 42 patients, respectively; p < 0.05) and >70% recurrentcarotid stenosis (6 of 32 vs. 0 of 29, respectively; p < 0.05) comparedwith patients undergoing CEA.

ICSS6

(2010)120-day data from1710 symptomatic patientsrandomized to CAS vs. CEA

Patients undergoing CAS (n Z 828) had a higher (vs.. CEA, n Z 821) riskof any stroke (65 vs. 35 events, or 7.7% vs. 4.1%, respectively; HR 1.92;95% CI 1.27e2.89; p Z 0.002), any stroke or death (72 vs. 40 events, or8.5% vs. 4.7%, respectively; HR 1.86; 95% CI 1.26e2.74; p Z 0.0001),all-cause death (19 vs. 7 events, or 2.3% vs. 0.8%, respectively; HR 2.76;95% CI 1.16e6.56; p Z 0.017).

CREST4

(2011)RCT of 2502 (1181 asymptomatic;1321 symptomatic) patients to CEA(n Z 1240) or CAS (n Z 1262)

Symptomatic patients undergoing CAS had a higher incidence of anyperiprocedural stroke (37 vs.. 21 events, or 5.5% � 0.9% vs. 3.2% � 0.7%,respectively; HR 1.74; 95% CI 1.02e2.98; p Z 0.04) and a higher incidenceof any periprocedural stroke or death (40 vs. 21 events or 6.0% � 0.9% vs.3.2% � 0.7%, respectively; HR 1.89; 95% CI 1.11e3.21; p Z 0.02)compared with patients undergoing CEA.

EVA-3S10

(2011)2-year carotid ultrasound follow-updata for 242 CAS patients and 265CEA patients of EVA-3S

The rate of carotid restenosis of �50% or occlusion was higher after CASthan after CEA (12.5% vs. 5.0%, respectively; time ratio 0.16; 95%CI 0.03e0.76; p Z 0.02).

EVA-3S: Endarterectomy vs. Angioplasty in patients with Symptomatic Severe Carotid Stenosis; CEA: carotid endarterectomy; CAS: carotidartery stenting; HR: hazard ratio; CI: confidence interval; SPACE: Stent-Protected Angioplasty vs. Carotid Endarterectomy; RCT: randomizedcontrolled trial; ICSS: International Carotid Stenting Study; CREST: Carotid Revascularization Endarterectomy vs. Stenting Trial.

718 Editorial

recurrent carotid stenosis rates8�10 (Table 1). CAS is alsoconsiderably more expensive than CEA.11 In addition,several recent meta-analyses have concluded that CAS isassociated with inferior outcomes compared with CEA.12�15

According to one meta-analysis (n Z 13 trials; 7484patients; 80% symptomatic),12 CAS is associated with anincreased risk of any stroke compared with CEA (RR 1.45;95% CI 1.06e1.99; I2 Z 40%). The conclusion reached wasthat “for every 1000 patients opting for CAS rather thanCEA, 19 more patients would have strokes”.12 These resultswere verified in another independent meta-analysis.13 Bothmeta-analyses, however, concluded that the superiority ofCEA over CAS disappeared in patients <70 years. Accordingto a recent large registry (n Z 47 752 CAS and CEA hospi-talisations matched by propensity score), the most appro-priate procedure in symptomatic patients with carotidartery stenosis is CEA, whereas CAS appears to be a suitableminimally invasive approach for asymptomatic patients.16

According to the recent inter-collegiate Australasian CASguidelines, “CASmaybe considered as a treatment option forpatientswith symptomatic severe carotid stenosiswhoare athigh risk of stroke, but are surgically unsuitable for CEA”.17

This includes specific patient subgroups and conditions,namely (1) post-radiation therapy, (2) block dissection of theneck, (3) in situ tracheostomy, (4) recurrent stenosisfollowing previous CEA, (5) severe cervical spine arthritis, (6)surgically inaccessible carotid stenosis (e.g., obesity and

high carotid bifurcation), (7) contralateral recurrent laryn-geal nerve injury and (8) contralateral internal carotid arteryocclusion.17 Apart from these conditions, CAS should not beconsidered as an alternative to CEA for the management ofsymptomatic carotid stenosis except in patients <70 yearsand those participating in randomised trials.17

Based on the results of meta-analyses,12�15 randomisedcontrolled trials6�10 and population-based studies,11,16 CASmay be an ‘alternative treatment’ but is clearly inferior toCEA in the majority of symptomatic patients.17 Unstablesymptomatic carotid plaques are associated with anincreased incidence of new ipsilateral silent embolic eventsafter CAS compared with CEA.18�20 In the absence of datashowing comparable risks of stroke and silent emboli forCAS, angioplasty and stenting should only be offered tosymptomatic patients when mitigating factors suggest anunacceptable risk with CEA.

It is likely that CAS will continue to improve with (1)better patient selection, (2) better embolic protectiondevices, (3) better stents (membrane or mesh covered), (4)technical improvements (e.g., avoiding aortic arch manip-ulations) and (5) additional operator experience.19 Adop-tion of all these may well improve CAS outcomes and makeit a fair alternative to CEA, at least in certain patientsubgroups. However, the current evidence indicates thatwe are not there yet, and it seems unfair to spin eitherCREST2 or the AHA/ASA guidelines1 to conclude that we are.

Editorial 719

Conflict of Interest

None.

Funding

None.

References

1 Brott TG, Halperin JL, Abbara S, Bacharach JM, Barr JD,Bush RL, et al. 2011, ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the manage-ment of patients with extracranial carotid and vertebral arterydisease a report of the American College of Cardiology Foun-dation/American Heart Association Task Force on practiceguidelines, and the American Stroke Association, AmericanAssociation of Neuroscience Nurses, American Association ofNeurological Surgeons, American College of Radiology, Amer-ican Society of Neuroradiology, Congress of NeurologicalSurgeons, Society of Atherosclerosis Imaging and Prevention,Society for Cardiovascular Angiography and Interventions,Society of Interventional Radiology, Society of NeuroInterven-tional Surgery, Society for Vascular Medicine, and Society forVascular Surgery Developed in Collaboration with the AmericanAcademy of Neurology and Society of Cardiovascular ComputedTomography. J Am Coll Cardiol 2011;57:e16e94.

2 Brott TG, Hobson 2nd RW, Howard G, Roubin GS, Clark WM,Brooks W, et al. CREST Investigators. Stenting versus endar-terectomy for treatment of carotid-artery stenosis. N Engl JMed 2010;363:11e23.

3 Webster’s New World College Dictionary. Available at: http://www.yourdictionary.com/alternative.

4 Silver FL, Mackey A, Clark WM, Brooks W, Timaran CH, Chiu D,et al. for the CREST Investigators. Safety of stenting andendarterectomy by symptomatic status in the carotid revascu-larization endarterectomy versus stenting trial (CREST). Stroke2011;42:675e80.

5 Aksoy O, Kapadia SR, Bajzer C, Clark WM, Shishehbor MH.Carotid stenting vs surgery: parsing the risk of stroke andMI. Cleve Clin J Med 2010;77:892e902.

6 Ederle J, Dobson J, Featherstone RL, Bonati LH, van derWorp HB, de Borst GJ, et al. International Carotid StentingStudy Investigators. Carotid artery stenting compared withendarterectomy in patients with symptomatic carotid stenosis(International Carotid Stenting Study): an interim analysis ofa randomised controlled trial. Lancet 2010;375:985e97.

7 Mas JL, Trinquart L, Leys D, Albucher JF, Rousseau H, Viguier A,et al. EVA-3S investigators. Endarterectomy versus angioplastyin patients with symptomatic severe carotid stenosis (EVA-3S)trial: results up to 4 years from a randomised, multicentre trial.Lancet Neurol 2008;7:885e92.

8 Steinbauer MG, Pfister K, Greindl M, Schlachetzki F, Borisch I,Schuirer G, et al. Alert for increased long-term follow-up aftercarotid artery stenting: results of a prospective, randomized,single-center trial of carotid artery stenting vs carotid endar-terectomy. J Vasc Surg 2008;48:93e8.

9 Eckstein HH, Ringleb P, Allenberg JR, Berger J, Fraedrich G,Hacke W, et al. Results of the Stent-Protected Angioplastyversus Carotid Endarterectomy (SPACE) study to treat symp-tomatic stenoses at 2 years: a multinational, prospective,randomised trial. Lancet Neurol 2008;7:893e902.

10 Arquizan C, Trinquart L, Touboul PJ, Long A, Feasson S,Terriat B, et al. For the EVA3-S Investigators. Restenosis is morefrequent after carotid stenting than after endarterectomy: theEVA-3S study. Stroke 2011;42:1015e20.

11 Young KC, Holloway RG, Burgin WS, Benesch CG. A cost-effectiveness analysis of carotid artery stenting comparedwith endarterectomy. J Stroke Cerebrovasc Dis 2010;19:404e9.

12 Murad MH, Shahrour A, Shah ND, Montori VM, Ricotta JJ.A systematic review and meta-analysis of randomized trials ofcarotid endarterectomy vs stenting. J Vasc Surg 2011;53:792e7.

13 Economopoulos KP, Sergentanis TN, Tsivgoulis G, Mariolis AD,Stefanadis C. Carotid artery stenting versus carotid endarter-ectomy: a comprehensive meta-analysis of short-term and long-term outcomes. Stroke 2011;42:687e92.

14 Meier P, Knapp G, Tamhane U, Chaturvedi S, Gurm HS. Shortterm and intermediate term comparison of endarterectomyversus stenting for carotid artery stenosis: systematic reviewand meta-analysis of randomised controlled trials. BMJ 2010;340:c467.

15 Bangalore S, Kumar S, Wetterslev J, Bavry AA, Gluud C,Cutlip DE, et al. Carotid artery stenting vs carotid endarterec-tomy: meta-analysis and diversity-adjusted trial sequentialanalysis of randomized trials. Arch Neurol 2011;68:172e84.

16 Giacovelli JK, Egorova N, Dayal R, Gelijns A, McKinsey J,Kent KC. Outcomes of carotid stenting compared with endar-terectomy are equivalent in asymptomatic patients and inferiorin symptomatic patients. J Vasc Surg 2010;52:906e13. e1ee4.

17 Bladin C, Chambers B, Crimmins D, Davis S, Donnan G, Frayne J,et al. Guidelines for patient selection and performance ofcarotid artery stenting: The Carotid Stenting GuidelinesCommittee: an inter-collegiate committee of the RACP (ANZAN,CSANZ), RACS (ANZSVS) and RANZCR. Intern Med J 2011 Feb 8[Epub ahead of print].

18 Yamada K, Yoshimura S, Kawasaki M, Enomoto Y, Asano T,Hara A, et al. Embolic complications after carotid arterystenting or carotid endarterectomy are associated with tissuecharacteristics of carotid plaques evaluated by magnetic reso-nance imaging. Atherosclerosis 2011;215:399e404.

19 Paraskevas KI, Mikhailidis DP, Veith FJ. Mechanisms to explainthe poor results of carotid artery stenting (CAS) in symptomaticpatients to date and options to improve CAS outcomes. J VascSurg 2010;52:1367e75.

20 Bonati LH, Jongen LM, Haller S, Flach HZ, Dobson J,Nederkoorn PJ, et al. New ischaemic brain lesions on MRI afterstenting or endarterectomy for symptomatic carotid stenosis:a substudy of the International Carotid Stenting Study (ICSS).Lancet Neurol 2010;9:353e62.

K.I. Paraskevas*Department of Vascular Surgery, Red Cross Hospital, 24, Al.

Papagou Street, Athens 14122, Greece*Corresponding author. Tel.: þ30 6977 776202;

fax: þ30 210 3215 792.E-mail address: paraskevask@hotmail.com

F.J. VeithDivision of Vascular Surgery, New York University Medical

Center, NY, USA

Division of Vascular Surgery, The Cleveland Clinic,Cleveland, USA

T.S. RilesNew York University, Langone Medical Center, NY, USA

W.S. MooreU.C.L.A. Medical Center, Los Angeles, CA, USA

Submitted 20 March 2011Accepted 21 March 2011

Available online 21 April 2011