Carotid artery stenosis is responsible for approximately 20% of strokes annually. Carotid revascularization, in appropriately selected patients, reduces this risk.¹ Two different approaches for carotid revascularization exist, carotid endarterectomy (CEA) and carotid artery stenting (CAS). Each of these revascularization modalities has relative risks and benefits. Recent studies have provided additional long-term data on the outcomes of these two approaches.

Much of the focus of comparative analyses of carotid artery revascularization has compared the early safety of the two interventions.² Specifically, CAS and CEA have competing peri-procedural risks. CAS is associated with a significantly greater peri-procedural minor stroke rate, while CEA is associated with an increased risk of myocardial infarction and cranial nerve palsies. Randomized trials have demonstrated similar short-term mortality rates and major stroke rates with the two procedures. There are other important, but less studied, trade-offs between the procedures in the peri-procedural period. For example, patients undergoing CAS may develop femoral access site complications and occasional bradycardia/hypotension after stent deployment due to direct mechanical carotid baroreceptor trauma. In comparison, patients undergoing CEA can experience neck hematomas as well as rare complications of anesthesia.

All of the above issues relate to comparative safety of CAS and CEA. However, it is important to keep in mind the purpose of carotid intervention: stabilization of plaque in order to prevent long-term stroke from vessel-to-vessel embolization. When deciding on the risks and benefits of a given intervention, the issues related to safety mentioned above must be carefully weighed against potential long-term efficacy of the procedure. The results from recently reported landmark trials and an updated meta-analysis assist us in this calculus.

Last year, the ACT-1 (Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease) and CREST (Carotid Revascularization Endarterectomy Versus Stenting) trials reported their final results. ACT-1 randomized 1453 asymptomatic carotid stenosis patients to CAS versus CEA in 3:1 fashion over an 8-year period.³ CREST randomized a mix of 2502 symptomatic and asymptomatic patients 1:1 to CAS versus CEA, also over an 8-year period.⁴ The trials were concordant in their findings, with both reporting results of long-term ipsilateral stroke excluding the peri-procedural period, the best measure of the efficacy of carotid revascularization (given the exclusion of peri-procedural safety events). ACT-1 demonstrated equal freedom from this long-term stroke endpoint in the CAS and CEA arms (97.8% vs. 97.3%, p = 0.51) at 5-year follow-up. Similarly, CREST revealed similar rates of long-term stroke after both procedures (6.9% vs. 5.6%, HR = 0.99, CI 0.64-1.52) with 10-year follow-up. CREST also provided the best information on restenosis after CAS and CEA to date. Kaplan-Meier estimated rates of 10-year revascularization or Doppler-detected restenosis were noted in similar proportions of patients undergoing both procedures (12.2% vs. 9.9%, HR = 1.24, CI = 0.91-1.70).

A recent meta-analysis aimed to integrate the information from these two trials with three prior randomized trials that have reported long-term outcomes. This analysis provided the absolute risks of various short and long-term adverse events associated with both procedures among a varied population of patients treated with the two modalities over a 10-year period (Table 1). The analysis confirmed the competing risks of stroke with CAS and myocardial infarction/cranial nerve palsy with CEA in the peri-procedural period. This study also examined the randomized data in a stratified fashion by symptomatic status. The combined endpoint of death, stroke, and myocardial infarction during the peri-procedural period and ipsilateral stroke during long-term follow-up favored CEA for symptomatic patients. However, no significant difference in this combined safety/efficacy endpoint was seen among asymptomatic patients. Even in the symptomatic subgroup, differences in overall outcome between the two therapies were primarily driven by peri-procedural stroke.

The overall conclusion to be gleaned from the recently published randomized trials and updated meta-analysis is that long-term stroke prevention is relatively equal between CAS and CEA. Thus, individualized decisions regarding treatment choice should initially be based on the risks of peri-operative complications. Validated risk scores may help with determining these risks in an objective fashion.^6,7 Next, anatomic factors that may strongly influence the technical difficulty associated with a given modality must be accounted for. For example, patients with high cervical carotid stenosis, low thoracic stenosis, prior endarterectomy, or a contralateral occlusion may have increased procedural difficulty with CEA. Alternatively, patients with heavily calcified stenosis, significant thrombotic burden, type II or III aortic arches, extreme angulation between the common carotid artery and internal carotid artery, or those that have anatomy making embolic protection difficult or impossible may have increased risks of procedural difficulty with CAS. Finally, several analyses have demonstrated the importance of operator experience with both procedures.^8,9 This should be integrated with both patient-specific risk scores that address factors such as age, symptomatic status, and other important comborbidities as well as case-specific anatomic characteristics to properly select the best revascularization modality in an individual patient.

Overall, annualized rates of ipsilateral stroke are roughly 0.5% per year after the peri-procedural period in patients undergoing carotid revascularization regardless of treatment modality. With no optimal medical therapy control arms in any large, prior randomized trial, it is difficult to know whether carotid revascularization represents a wise clinical decision in most asymptomatic patients. The CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) trial aims to answer this question and is currently enrolling.

Table 1: Absolute Risk of Outcomes of Major Interest From Five Randomized Trials

Outcome of Interest	Number of Events/Number of Patients, (Absolute Event Rate, %)		Number Needed to Treat/Harm for CAS	P-value
	CAS group	CEA group
Aggregate Efficacy/ Safety Outcome#	295/3636 (8.1)	218/2890 (7.5)	-	0.14
Peri-procedural any stroke + non peri-procedural ipsilateral stroke	275/3636 (7.6)	161/2890 (5.6)	50 (NNH)	<0.001
Peri-procedural any stroke	169/3636 (4.6)	73/2890 (2.5)	47 (NNH)	<0.001
Peri-procedural minor stroke	124/3636 (3.4)	44/2890 (1.5)	52 (NNH)	<0.001
Peri-procedural death	26/3636 (0.7)	16/2890 (0.5)	-	0.48
Peri-procedural MI	24/3636 (0.6)	48/2890 (1.6)	99 (NNT)	0.002
Peri-procedural CN palsy	9/3636 (0.2)	135/2890 (4.7)	22 (NNT)	<0.001
Peri-procedural neurological injury	178/3636 (4.9)	208/2890 (7.2)	43 (NNT)	0.02
Peri-procedural neck hematoma	20/3469 (0.6)	53/2723 (1.9)	73 (NNT)	<0.001
Composite peri-procedural safety outcome##	224/3636 (6.2)	263/2890 (9.1)	34 (NNT)	0.008
Long-term stroke in any territory (includes periprocedural stroke)	305/3636(8.4)	200/2890 (6.9)	68  (NNH)	<0.001
Long-term death	429/3636 (11.8)	357/2890 (12.3)	-	0.18

References

1. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol 2011;57:1002-44.
2. Meier P, Knapp G, Tamhane U, Chaturvedi S, Gurm HS. Short term and intermediate term comparison of endarterectomy versus stenting for carotid artery stenosis: systematic review and meta-analysis of randomised controlled clinical trials. BMJ 2010;340:c467
3. Rosenfield K, Matsumura JS, Chaturvedi S, et al. Randomized trial of stent versus surgery for asymptomatic carotid stenosis. N Engl J Med 2016;374:1011-20.
4. Brott TG, Howard G, Roubin GS, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med 2016;374:1021-31.
5. Sardar P, Chatterjee S, Aronow HA, et al. Carotid artery stenting versus endarterectomy for stroke prevention: a meta-analysis of clinical trials. J Am Coll Cardiol 2017. [Epub ahead of print]
6. Hawkins BM, Kennedy KF, Giri J, et al. Pre-procedural risk quantification for carotid stenting using the CAS score: a report from the NCDR CARE Registry. J Am Coll Cardiol 2012;60:1617-22.
7. Wimmer NJ, Spertus JA, Kennedy KF, et al. Clinical prediction model suitable for assessing hospital quality for patients undergoing carotid endarterectomy. J Am Heart Assoc 2014;3:e000728.
8. Kumamaru H, Jalbert JJ, Nguyen LL, et al. Surgeon case volume and 30-day mortality after carotid endarterectomy among contemporary medicare beneficiaries: before and after national coverage determination for carotid artery stenting. Stroke 2015;46:1288-94.
9. Nallamothu BK, Gurm HS, Ting HH, et al. Operator experience and carotid stenting outcomes in Medicare beneficiaries. JAMA 2011;306:1338-43.

Keywords: Anesthesia, Angioplasty, Bradycardia, Calculi, Carotid Artery, Common, Carotid Artery, Internal, Carotid Stenosis, Constriction, Pathologic, Cranial Nerve Diseases, Cranial Nerves, Embolism, Endarterectomy, Carotid, Hematoma, Hypotension, Myocardial Infarction, Pressoreceptors, Risk Assessment, Stents, Stroke, Aneurysm

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