Leading article

Endarterectomy versus carotid stentingA. R. NaylorVascular Surgery Group, Division of Cardiovascular Sciences, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK(e-mail: ross.naylor@uhl-tr.nhs.uk)

Published online 8 November 2011 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.7747

‘Honest disagreement is often a good signof progress’

Mahatma Gandhi (1869–1948)

Some 21 randomized trials involv-ing 19 279 patients have evaluatedthe roles of carotid endarterectomy(CEA), best medical therapy (BMT)and carotid artery stenting (CAS)in patients with symptomatic andasymptomatic carotid disease. Before2011, the data were generally inter-preted as CEA being preferable in‘average-risk’ symptomatic patientswith 50–99 per cent stenoses and in‘average-risk’ asymptomatic patientswith 60–99 per cent stenoses. CASwas preferred in symptomatic patientsdeemed ‘high risk’ for CEA, andBMT thought safer in asymptomaticpatients considered ‘high risk’ forCEA. This consensus was, however,somewhat fragile as there was anuneasy relationship between surgeonswho wanted guidelines to remainunchanged, radiological intervention-ists who argued that the benefits ofCAS were being withheld, and pur-chasers of healthcare, wary of changesin practice being driven by the ‘medi-cal industrial complex’ rather than evi-dence. Liberalizing CAS indicationsmight also have financial implicationsfor surgeons and interventionists inprivately funded healthcare systems.

This consensus effectively collap-sed following the 2011 US Foodand Drug Administration approvalof the RX Acculink Carotid Stentsystem (Abbott Laboratories, AbbottPark, Illinois, USA) in average-riskpatients1. Along with 2011 guidelinesfrom the American Heart Association

(AHA)2,3, CAS was declared com-parable with CEA in the treatmentof average-risk symptomatic andasymptomatic patients. Other coun-tries have advocated a more restrictedexpansion of CAS. Guidelines fromAustralia and New Zealand concludedthat, although CAS was appropri-ate in symptomatic patients aged lessthan 70 years and in ‘high-risk forCEA’ symptomatic patients, they didnot recommend CAS in average-risk,asymptomatic patients4. The 2011National Institute for Health andClinical Excellence guidelines advisedthat the evidence supported CAS inrecently symptomatic patients (pro-vided that arrangements were madefor clinical governance, audit andresearch), but that CAS should beused only in asymptomatic patientsin randomized trials or by ‘specialarrangement’5,6. Given past experi-ence, however, it seems likely that therest of the world will adopt guidelinessimilar to those of the AHA.

Those familiar with the literaturewill be well versed in what the ran-domized trials have told us, but manymay be less familiar with what theyhave not told us. Current evidenceoffers ten key observations7–10:

• CAS is associated with a twofoldincrease in procedural death/stroke.

• CEA is associated with a twofoldincrease in procedural myocardialinfarction (MI).

• When the 30-day risk of death/stroke is expanded to include MI,there is no difference between CEAand CAS.

• Procedural risks after CAS inpatients aged less than 70 years

are similar to those after CEA,whereas the risk of death/stroke issignificantly greater after CAS inpatients older than 70 years.

• Following successful CAS, long-term stroke risks are similar to thoseof CEA.

• Restenosis rates are higher follow-ing CAS, but this does not translateinto an increased risk of ipsilateralstroke.

• CAS involves a considerable learn-ing curve (perhaps 50 procedures).

• There is now better information onthe type of patient unsuitable forCAS (especially for novices).

• CEA is associated with a higher rateof cranial nerve injury.

• CAS is associated with a five-fold excess risk of new andpersisting lesions on magneticresonance imaging (MRI) com-pared with CEA.The inevitable consequences of the

2011 AHA recommendations will bethat a greater proportion of ‘average-risk’ patients will be treated by CAS.The majority treated will be asymp-tomatic and the volume of carotidinterventions will increase worldwide.A number of issues remain unre-solved, however, with far-reachingimplications. The first (whether massintervention in asymptomatic patientsis clinically effective) is outwith theremit of this article, but there isgrowing evidence that the annual riskof stroke in patients receiving BMThas declined considerably since therandomized trials were recruiting11.Identifying that smaller cohort ofasymptomatic patients who are at highrisk of stroke, in whom to target CEAor CAS, should really be a priority.

2011 British Journal of Surgery Society Ltd British Journal of Surgery 2012; 99: 149–151Published by John Wiley & Sons Ltd

150 A. R. Naylor

The failure of nearly every guide-line to address the need for inter-vention in the hyperacute periodafter onset of symptoms repre-sents an area of major weakness.The traditional 6-month thresh-old for intervention is now obso-lete. The question is whether CEAor CAS is safer in the first7–14 days after onset of symptomswhen the patient gains most fromintervention11. The Carotid StentingTrialists Collaboration observed thatpatients treated within 14 days in theEndarterectomy Versus Angioplastyin Patients with Symptomatic SevereCarotid Stenosis (EVA-3S) trial,Stent-Protected Angioplasty versusCarotid Endarterectomy (SPACE)trial and International Carotid Stent-ing Study (ICSS) were three timesmore likely to suffer death or strokeafter CAS than after CEA8. It mightbe argued, for now, that CEA remainsthe safer intervention for the majorityof patients in the hyperacute periodirrespective of age, whereas CAS hasa more prominent role thereafter.Establishing the significance of newdiffusion-weighted lesions seen afterCAS (five times more common thanafter CEA10) has also been conve-niently ignored. Few quality studieshave evaluated whether these lesionsare associated with cognitive impair-ment, but these are urgently required.It could be that new ischaemiclesions, which occur despite protec-tion devices, carry an adverse prog-nosis (such as dementia) and maybecome as clinically important asperioperative MI.

The prevalence of procedural MIwas influential in the AHA approvingCAS in average-risk patients. Withoutits inclusion, CEA would have provedstatistically superior to CAS in symp-tomatic patients in the Carotid Revas-cularization Endarterectomy versusStenting Trial (CREST)7. Surgeonsand neurologists objected to the

inclusion of MI within CREST’sprimary endpoint, but evidence sug-gests that this may have been a reason-able decision, although perhaps notfor the explanations given. Unlikeearlier randomized trials, CRESTincluded perioperative MI (definedas chest pain plus raised enzymelevels or new electrocardiographic(ECG) abnormalities) or ‘chemical’MI (raised enzyme levels but no clin-ical/ECG abnormalities). In the 2440patients with neither a proven MInor a ‘chemical’ MI, the procedu-ral mortality rate was 0·4 per cent12.The mortality rate then increased to2·2 per cent at 1 year and 6·7 per centat 4 years. By contrast, 20 patientswith ‘chemical’ MI had a periop-erative mortality rate of 5 per cent,the cumulative mortality rate increas-ing to 25 per cent at 5 years. Therewere 42 patients with a proven MI.Here the perioperative mortality ratewas 2·4 per cent, with the cumu-lative mortality rate increasing to19 per cent at 4 years. CREST con-cluded that perioperative MI was animportant predictor of late mortality.However, because CEA was associ-ated with a doubling of the risk ofperioperative MI, it was assumed thatCEA would be associated with worselate mortality rates. Notwithstand-ing small numbers, CREST actu-ally showed that, in 62 patients withproven or ‘chemical’ MI, there were13 late deaths (CEA 7, CAS 6)12. Thestudy did not provide any evidencethat patients undergoing CEA whosuffered a perioperative MI faced anincreased risk of late death. It didshow that perioperative MI occurredmore commonly in patients with agreater cardiovascular burden or renalimpairment, and that perioperativeMI was a marker for late death, irre-spective of whether the patient under-went CEA or CAS.

How should these data be inter-preted? The highest priority has to

be given to treating symptomaticpatients as soon as possible after theonset of symptoms. For most cen-tres, this will probably mean expeditedCEA, but experienced CAS centres(with audited outcomes) may preferstenting. However, it would be uneth-ical to actively delay treatment so thatsurgeons or interventionists couldundertake procedures with a lowerrisk in order to work off their learningcurve. The management of asymp-tomatic patients remains controver-sial and will vary according to healthsystem. It is, however, a very real pos-sibility that trials currently random-izing asymptomatic patients to CEAor CAS without including an ade-quately powered limb for BMT couldbe rendered obsolete when they com-plete. Using Asymptomatic CarotidAtherosclerosis Study (ACAS) data,even if CEA/CAS could be performedwith a 0 per cent risk, 92 per centof all interventions would still beunnecessary11.

Finally, one new message hasemerged following the publicationof CREST. Asymptomatic patientswho have a greater cardiovascu-lar burden face a higher risk ofprocedural MI and a significantlyreduced long-term survival (irrespec-tive of whether they are treated byCEA or CAS). It may, therefore, besafer to treat these patients conser-vatively. To paraphrase Henry Bar-nett: ‘Carotid procedures may triggerMIs, but they cannot prevent them’13.Accordingly, case selection remainsas important in 2011 as it did in1991 when evidence replaced ‘intu-itive reasoning’ in determining howbest to manage patients with carotiddisease.

Acknowledgements

The author declares no conflict ofinterest.

2011 British Journal of Surgery Society Ltd www.bjs.co.uk British Journal of Surgery 2012; 99: 149–151Published by John Wiley & Sons Ltd

Endarterectomy versus carotid stenting 151

References

1 US Food and Drug Administration.FDA Expands Approved Use for CarotidStent. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm254430.htm [accessed 21June 2011].

2 Furie KL, Kasner SE, Adams RJ,Albers GW, Bush RL, Fagan SCet al.; American Heart AssociationStroke Council, Council onCardiovascular Nursing, Council onClinical Cardiology, andInterdisciplinary Council on Qualityof Care and Outcomes Research.Guidelines for the prevention ofstroke in patients with stroke ortransient ischemic attack: a guidelinefor healthcare professionals from theAmerican Heart Association/American Stroke Association. Stroke2011; 42: 227–276.

3 Goldstein LB, Bushnell CD,Adams RJ, Appel LJ, Braum LT,Chaturvedi S et al.; American HeartAssociation Stroke Council, Councilon Cardiovascular Nursing, Councilon Epidemiology and Prevention,Council for High Blood PressureResearch, Council on PeripheralVascular Disease, andInterdisciplinary Council on Qualityof Care and Outcomes Research.Guidelines for the primary preventionof stroke: a guideline for healthcare

professionals from the AmericanHeart Association/American StrokeAssociation. Stroke 2011; 42:517–584.

4 Bladin C, Chambers B, Crimmins D,Davis S, Donnan G, Frayne J et al.Guidelines for patient selection andperformance of carotid arterystenting. Intern Med J 2011; 41:344–347.

5 National Institute for Health andClinical Excellence. Carotid ArteryStent Placement for SymptomaticExtracranial Carotid Stenosis –Overview. http://www.nice.org.uk/guidance/IP/8/overview [accessed21 June 2011].

6 National Institute for Health andClinical Excellence. Carotid ArteryStent Placement for AsymptomaticExtracranial Carotid Stenosis –Overview. http://www.nice.org.uk/guidance/IP/881/overview [accessed21 June 2011].

7 Brott TG, Hobson RW, Howard G,Roubin GS, Clark WM, Brooks Wet al. Stenting versus endarterectomyfor treatment of carotid-arterystenosis. N Engl J Med 2010; 363:11–23.

8 Carotid Stenting TrialistsCollaboration, Bonati LH, Dobson J,Algra A, Branchereau A, Chatellier Get al. Short term outcome afterstenting versus carotidendarterectomy for symptomatic

carotid stenosis: preplannedmeta-analysis of individualpatient data. Lancet 2010; 376:1062–1073.

9 Smout J, MacDonald S, Weir G,Stansby G. Carotid artery stenting:relationship between experience andcomplication rate. Int J Stroke 2010;5: 477–482.

10 Bonati LH, Jongen LM, Haller S,Flach HZ, Dobson J, Nederkoorn PJet al.; ICSS-MRI study group. Newischaemic brain lesions on MRI afterstenting or endarterectomy forsymptomatic carotid stenosis: asubstudy of the International CarotidStenting Study (ICSS). Lancet Neurol2010; 9: 353–362.

11 Naylor AR. What is the current statusof invasive treatment of extracranialcarotid artery disease? Stroke 2011;42: 2080–2085.

12 Blackshear JL, Cutlip DE,Roubin GS, Hill MD,Leimgruber PP, Begg RJ et al.Myocardial infarction after carotidstenting and endarterectomy: resultsfrom the Carotid RevascularizationEndarterectomy versus StentingTrial. Circulation 2011; 123:2571–2578.

13 Barnett HJM, Pelz DM, Lownie SP.Reflections by contrarians on thepost-CREST evaluation of carotidstenting for stroke prevention. Int JStroke 2010; 5: 455–456.

2011 British Journal of Surgery Society Ltd www.bjs.co.uk British Journal of Surgery 2012; 99: 149–151Published by John Wiley & Sons Ltd