FROM THE ARCHIVES

Carotid Artery Stenting vs Carotid Endarterectomy

B ANGALORE AND COLLEAGUES HAVE PRE-sented an extensive analysis of 13 random-ized clinical trials with an aggregate of al-most 7500 patients and reached theconclusion that carotid artery stenting

(CAS) confers an increased risk of stroke, death, or myo-cardial infarction compared with carotid endarterec-tomy when treating carotid stenosis. Although these stud-ies include a variety of symptomatic and asymptomaticpatients treated in numerous geographic locations, theauthors have presented an elegant statistical analysis thatallows the reader to consider the various biases that maybe present in each study. However, certain concernsshould be considered when evaluating the treatment op-tions discussed therein.

These studies have subtle differences in their designsand defined endpoints. Some have included only symp-

tomatic patients, whereas the most recent large study hasincluded approximately even proportions of sympto-matic and asymptomatic patients.1 Symptomatic pa-tients are known to have a higher risk of stroke with medi-cal treatment and endarterectomy. That same observationhas not been established for CAS. However, the Ameri-can Heart Association has established guidelines for treat-ing asymptomatic carotid artery stenosis that suggest acomplication rate of less than 3% to improve the out-come compared with standard medical treatment.2 Thatsame guideline should be maintained for open surgicalor catheter-based revascularization techniques. In addi-tion, most of these reports include the endpoint of myo-cardial infarction that had not been considered in priorstudies. Interestingly, the definition of myocardial in-farction has changed with time due to use of the sensi-tive troponin isotope that can detect minor enzymatic

Archives of Neurology

Carotid Artery Stenting vs Carotid Endarterectomy: Meta-analysis and Diversity-Adjusted TrialSequential Analysis of Randomized Trials

Sripal Bangalore, MD, MHA; Sunil Kumar, MD; Jørn Wetterslev, MD, PhD; Anthony A. Bavry, MD, MPH;Christian Gluud, MD, DMSci; Donald E. Cutlip, MD; Deepak L. Bhatt, MD, MPH

Background: The role of carotid artery stenting (CAS) when compared with carotid endarterectomy (CEA) is controversial,with recent trials showing an increased risk of harm with CAS.

Objective: To evaluate the periprocedural and intermediate to long-term benefits and harms of CAS compared with CEA.

Data Sources and Study Selection: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials searches forrandomized clinical trials until June 2010 of CAS compared with CEA for carotid artery disease. Periprocedural (�30-day)outcomes (death, myocardial infarction [MI], or stroke; death or any stroke; any stroke; and MI) and intermediate to long-term outcomes (outcomes as in the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy[SAPPHIRE] trial: composite of periprocedural death, MI, or stroke plus ipsilateral stroke or death thereafter; periproce-dural death or stroke plus ipsilateral stroke thereafter; death or any stroke; and any stroke) were evaluated.

Data Extraction: Two of us independently extracted data in duplicate. Baseline characteristics, inclusion and exclusion cri-teria, use of an embolic protection device, US vs non-US study, and the earlier-mentioned outcomes of interest were ex-tracted from each trial.

Data Synthesis: We identified 13 randomized clinical trials randomizing 7477 participants. Carotid artery stenting was as-sociated with an increased risk of periprocedural outcomes of death, MI, or stroke (odds ratio=1.31; 95% confidence inter-val, 1.08-1.59), 65% and 67% increases in death or stroke and any stroke, respectively, but with 55% and 85% reductions inthe risk of MI and cranial nerve injury, respectively, when compared with CEA. The trial sequential monitoring boundarywas crossed by the cumulative z curve, suggesting firm evidence for at least a 20% relative risk increase of periproceduraldeath or stroke and any stroke and at least a 15% reduction in MI with CAS compared with CEA. Similarly, CAS was asso-ciated with 19%, 38%, 24%, and 48% increases in the intermediate to long-term outcomes of SAPPHIRE-like outcome, peri-procedural death or stroke and ipsilateral stroke thereafter, death or any stroke, and any stroke, respectively. The trial se-quential monitoring boundary was crossed by the cumulative z curve, suggesting firm evidence for at least a 20% relativerisk increase of any stroke.

Conclusions: In this largest and most comprehensive meta-analysis to date using outcomes that are standard in contem-porary studies, CAS was associated with an increased risk of both periprocedural and intermediate to long-term outcomes,but with a reduction in periprocedural MI and cranial nerve injury. Strategies are urgently needed to identify patients whoare best served by CAS vs CEA.

Arch Neurol. 2011;68(2):172-184. Published online October 11, 2010.

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changes before infarction occurs. Also, some of these stud-ies attempt to equate a cranial nerve injury with a stroke.Although this comparison is advocated by some, it re-mains simplistic to consider a symptom such as tran-sient hoarseness lasting 2 weeks to be of the same sever-ity as the lost functional status of a hand that may beclassified as a minor stroke. The studies should also con-sider the femoral access pathologic complications thatcan occur after CAS. This morbidity may create more dys-function than would a minor stroke in some patients.

We should also consider the value of further clinicaltrials in this area of carotid revascularization. Althoughnumerous clinical trials have been conducted to evalu-ate these treatment modalities, CAS likely does not con-fer greater benefit for the general population but shouldbe applied to specific subgroups of patients as deter-mined by a physician familiar with the application of CASand carotid endarterectomy. The physiologic risk of bothprocedures is equivalent at best but more likely is greaterfor CAS. Also, the financial cost is likely greater for CAS,prompting the question as to whether we should con-tinue to allocate resources to perform further clinical trialsfor a procedure that might have no appreciable gain forour patients. It may be time to limit the use of addi-

tional resources for such trials until a specific leap in treat-ment results can realistically be obtained.

Accepted for Publication: December 6, 2010.Author Affiliation: Section of Vascular Surgery andEndovascular Therapy, Department of Surgery, Schoolof Medicine, University of Alabama at Birmingham,Birmingham.Correspondence: Dr Jordan, Section of Vascular Surgeryand Endovascular Therapy, Department of Surgery, Schoolof Medicine, University of Alabama at Birmingham, Build-ing Code BDB 503, 1808 7th Ave South, Birmingham,AL 35294 (wdjordan@uab.edu).Financial Disclosure: None reported.

REFERENCES

1. Brott TG, Hobson RW II, Howard G, et al; CREST Investigators. Stenting versusendarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363(1):11-23.

2. Moore WS, Barnett HJM, Beebe HG, et al. Guidelines for carotid endarterectomy:a multidisciplinary consensus statement from the ad hoc committee, AmericanHeart Association. Stroke. 1995;26(1):188-201.

William D. Jordan, MD

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