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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Surgery
Policy Number:053
Effective Date: 06/13/2017
Original Policy Date:11/22/2004
Last Review Date:06/09/2020
Date Published to Web: 04/28/2015
Subject:
Extracranial Carotid Artery Stenting

Description:
_______________________________________________________________________________________

IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

__________________________________________________________________________________________________________________________

Carotid artery angioplasty with stenting is a treatment for carotid stenosis that is intended to prevent a future stroke. It is an alternative to medical therapy and a less-invasive alternative to carotid endarterectomy (CEA).


PopulationsInterventionsComparatorsOutcomes
Individuals:
    • With carotid artery stenosis
Interventions of interest are:
    • Carotid artery stenting
Comparators of interest are:
    • Carotid endarterectomy
Relevant outcomes include:
    • Overall survival
    • Morbid events
    • Treatment-related mortality
    • Treatment-related morbidity

Background

Combined with optimal medical management, carotid angioplasty with or without stenting has been evaluated as an alternative to carotid endarterectomy (CEA). Carotid artery stenting (CAS) involves the introduction of coaxial systems of catheters, microcatheters, balloons, and other devices. The procedure is most often performed through the femoral artery but a transcervical approach can also be used to avoid traversing the aortic arch. The procedure typically takes 20 to 40 minutes. Interventionalists almost uniformly use an embolic protection device (EPD) to reduce the risk of stroke caused by thromboembolic material dislodged during CAS. EPDs can be deployed proximally (with flow reversal) or distally (using a filter). Carotid angioplasty is rarely performed without stent placement.

The proposed advantages of CAS over CEA include:

    • General anesthesia is not used (although CEA can be performed under local or regional anesthesia)
    • Cranial nerve palsies are infrequent sequelae (although almost all following CEA resolve over time)
    • Simultaneous procedures may be performed on the coronary and carotid arteries.
Regulatory Status

A number of CAS and EPDs have been approved by the U.S. Food and Drug Administration (FDA) through the premarket approval (PMA) or the 510(k) process.Table 1 lists the original PMA's with product code NIM and Table 2 lists 510(k) approvals with product code NTE.

Table 1. FDA Premarket Approvals for Carotid Artery Stents and Embolic Protection Devices
ManufacturerDevicePMAPMA Date
Cordis Corp.Cordis Precise Nitinol Stent SystemP030047Sept 2006
Abbott VascularAcculink Carotid Stent System and Rx Acculink Carotid Stent SystemP040012Aug 2004
Abbott VascularXACT Carotid Stent SystemP040038Sep 2005
Boston Scientific Corp.Carotid Wallstent Monorail EndoprosthesisP050019Oct 2008
Boston Scientific Corp.Endotex Nexstent Carotid Stent and Delivery System and Endotex Carotid Stent and Monorail Delivery SystemP050025Oct 2006
Medtronic VascularjProtege GPS and Protege Rx Carotid Stent SystemsP060001Jan 2007
Medtronic VascularExponent Self-Expanding Carotid Stent System with Over-the-Wire or Rapid-Exchange Delivery SystemP070012Oct 2007
Silk Road Medical, Inc.Enroute Transcarotid Stent SystemP140026May 2015
W. L Gore & Associates, Inc Gore Carotid StentGore Carotid StentP180010Nov 2018

PMA: Premarket approval

Table 2. FDA 510(k) Carotid Artery Stents and Embolic Protection Devices
ManufacturerStents and Devices510(k) NumberPMA/510(k) Date
carotid stents
Guidant, now Abbott VascularAccunet and RX AccunetEmbolic protection systemK042218Aug 2004
Guidant, now Abbott VascularRx Accunet 2 Embolic Protection SystemK042908Nov 2004
Guidant, now Abbott VascularRx Accunet Embolic Protection SystemK052165Aug 2005
Abbott VascularEmboshield® embolic protection systemK052454Sep 2005
Cordis Corp.AngioGuardä XP and RX emboli capture guidewire systemsK062531Sep 2006
Boston ScientificFilterWire EZ™ embolic protection systemK063313Dec 2006
EV3 IncSpiderxK052659Feb 2007
EV3 IncSpidefxK063204Nov 2007
GOREGORE® Flow Reversal SystemK083300Feb 2009
GOREGORE® Embolic FilterK103500May 2011
Medtronic/InvatecMo.Ma® Ultra Proximal Cerebral Protection DeviceK092177Oct 2009
Silk Road MedicalENROUTE™ Transcarotid Stent System and ENROUTE Transcarotid Neuroprotection SystemK143072Feb 2015
Gardia MedicalWirionK143570Jun 2015
Abbott VascularRx Accunet Embolic Protection SystemK153086Nov 2015
Silk Road Medical, Inc.Enroute Transcarotid Neuroprotection SystemK153485Mar 2016
Gardia Medical Ltd.WirionK180023Mar 2018
Contego Medical, LLCPaladin Carotid Post-Dilation Balloon System With Integrated Embolic Protection (Paladin System)K181128Sep 2018
Contego Medical, LLCVanguard lep Peripheral Balloon Angioplasty System With Integrated Embolic ProtectionK181529Dec 2018
Abbott VascularEmboshield Nav6 Embolic Protection System, Barewire Filter Delivery WiresK191173Jul 2019

FDA: Food and Drug Administration; PMA: premarket approval.

Each FDA-approved carotid stent is indicated for combined use with an EPD to reduce risk of stroke in patients considered at increased risk for periprocedural complications from CEA who are symptomatic with greater than 50% stenosis, or asymptomatic with greater than 80% stenosis with degree of stenosis assessed by ultrasound or angiogram, with computed tomography angiography also used. Patients are considered at increased risk for complications during CEA if affected by any item from a list of anatomic features and comorbid conditions included in each stent system’s Information for Prescribers.

The RX Acculinkä Carotid Stent System is also approved for use in conventional risk patients (not considered at increased risk for complications during CEA) with symptoms and 70% or more stenosis by ultrasound or 50% or more stenosis by angiogram, and asymptomatic patients with 70% or more stenosis by ultrasound or 60% or more stenosis by angiogram.

The FDA-approved stents and EPDs differ in the deployment methods used once they reach the target lesion, with the rapid exchange devices designed for more rapid stent and filter expansion. The FDA has mandated postmarketing studies for EPDs, including longer follow-up for patients already reported to the FDA and additional registry studies, primarily to compare outcomes as a function of clinician training and facility experience. Each manufacturer’s system is available in various configurations (eg, straight or tapered) and sizes (diameters and lengths) to match the vessel lumen that will receive the stent.

In 2015, the ENROUTE™Transcarotid Neuroprotection System was cleared for marketing by the FDA through the 510(k) process.ENROUTE™is a flow reversal device designed to be placed via direct carotid access.

FDA product codes: NIM (stents) and NTE (EPDs).

Related Policies

  • Endovascular Therapies for Extracranial Vertebral Artery Disease (Policy #147 in the Surgery Section)
  • Endovascular Procedures for Intracranial Arterial Disease (Atherosclerosis and Aneurysms) (Policy #123 in the Surgery Section)

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

I. Carotid angioplasty with associated stenting and embolic protection is considered medically necessary in members with:
    • 50% to 99% stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET] measurement); AND
    • symptoms of focal cerebral ischemia (transient ischemic attack or monocular blindness) in previous 120 days, symptom duration less than 24 hours, or nondisabling stroke; AND
    • anatomic contraindication for carotid endarterectomy (e.g., prior radiotherapy or neck surgery, lesions surgically inaccessible, spinal immobility, or tracheostomy).

II. Carotid angioplasty with associated stenting and embolic protection is considered investigational for all other indications, including but not limited to, members with carotid stenosis who are suitable candidates for carotid endarterectomy and members with carotid artery dissection.

III. Carotid angioplasty without associated stenting and embolic protection is considered investigational for all indications, including but not limited to, members with carotid stenosis who are suitable candidates for carotid endarterectomy and members with carotid artery dissection.


Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

The intent of the second investigational policy statement is that carotid angioplasty with embolic protection but without stenting is investigational. There may be unique situations where the original intent of surgery was to perform carotid angioplasty with stenting and embolic protection, but anatomic or other considerations prohibited placement of the stent.


Medicare Coverage:
**Extracranial Carotid Artery Stenting must be performed in a CMS approved facility.

Concurrent with Carotid Stent Placement in Food and Drug Administration (FDA)-Approved Category B Investigational Device Exemption (IDE) Clinical Trials.

Effective July 1, 2001, Medicare covers PTA of the carotid artery concurrent with carotid stent placement when furnished in accordance with the FDA-approved protocols governing Category B IDE clinical trials. PTA of the carotid artery, when provided solely for the purpose of carotid artery dilation concurrent with carotid stent placement, is considered to be a reasonable and necessary service when provided in the context of such a clinical trial.

Concurrent with Carotid Stent Placement in FDA-Approved Post Approval Studies

Effective October 12, 2004, Medicare covers PTA of the carotid artery concurrent with the placement of an FDA-approved carotid stent for an FDA-approved indication when furnished in accordance with FDA-approved protocols governing post-approval studies. CMS determines that coverage of PTA of the carotid artery is reasonable and necessary under these circumstances.

Effective March 17, 2005, Medicare covers PTA of the carotid artery concurrent with the placement of an FDA-approved carotid stent with embolic protection for the following:

Patients who are at high risk for CEA and who also have symptomatic carotid artery stenosis ≥ 70%. Coverage is limited to procedures performed using FDA-approved carotid artery stenting (CAS) systems and FDA-approved or -cleared (effective December 9, 2009) embolic protection devices. If deployment of the embolic protection device is not technically possible, and not performed, then the procedure is not covered by Medicare (effective December 9, 2009);

Patients who are at high risk for CEA and have symptomatic carotid artery stenosis between 50% and 70%, in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), as a routine cost under the clinical trials policy (Medicare National Coverage Determination (NCD) Manual 310.1), or in accordance with the NCD on (CAS) post-approval studies (Medicare NCD Manual 20.7);

Patients who are at high risk for CEA and have asymptomatic carotid artery stenosis ≥ 80%, in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), as a routine cost under the clinical trials policy (Medicare NCD Manual 310.1), or in accordance with the NCD on CAS post- approval studies (Medicare NCD Manual 20.7).

Coverage is limited to procedures performed using an FDA-approved CAS, stents and FDA-approved or -cleared embolic protection devices. The use of an FDA-approved or cleared embolic protection device is required. If deployment of the embolic protection device is not technically possible, and not performed, then the procedure is not covered by Medicare.

For additional information and eligibility, refer to National Coverage Determination (NCD) for Percutaneous Transluminal Angioplasty (PTA) (20.7). Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?ncdid=201.


[RATIONALE: This policy was created in 2004 and has been updated regularly with a literature review of the PubMed database. The most recent literature update was performed through March 13, 2020.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function - including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Clinical Context and Therapy Purpose

The purpose of carotid artery stenting is to provide a treatment option for carotid artery stenosis that is an alternative to medical therapy and a less-invasive alternative to carotid endarterectomy.

The question addressed in this policy is: Does the use of carotid artery stenting improve the net health outcome in patients with carotid stenosis?

The following PICO was used to select literature to inform this policy.

Patients

The relevant population of interest is individuals with carotid artery stenosis

Interventions

The therapy being considered is carotid artery stenting

Comparators

The comparator of interest is carotid endarterectomy

Outcomes

The general outcomes of interest are overall survival, morbid events, treatment-related mortality, and treatment-related morbidity.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

    • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs and systematic reviews;
    • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
    • To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
    • Studies with duplicative or overlapping populations were excluded.
Risk-Benefit Ratio of Invasive Carotid Procedures

Endovascular carotid artery stenting (CAS) and surgical endarterectomy (CEA) for carotid artery disease trades procedure-related harms of stroke and death for the benefit of reduced stroke risk over subsequent years; the balance determines whether either intervention will result in a net clinical benefit. That balance has been scrutinized for CEA but not for CAS; accordingly, results from trials of CEA must be extrapolated to assess outcomes for CAS.

Review of Evidence

A series of landmark clinical trials from the late 1980s through the 1990s compared the benefits and harms of CEA with best medical therapies then available in symptomatic and asymptomatic individuals with carotid artery stenosis.1,2,3,4,5,6,7, Those trial results defined the magnitude of risk reduction for stroke and the periprocedural stroke and death rates for 30 days, that must be offset to achieve a net clinical benefit (benefit outweighing harm),less than 3% for asymptomatic (>60% stenosis), and less than 6% for symptomatic patients (50%-69% or 70%-99% stenosis). Furthermore, because periprocedural harms are immediate, but benefit accrues over time, a net clinical benefit is obtained only for those patients surviving long enough to counterbalance the immediate harms. The necessary life expectancy defined by the trial duration needed to demonstrate benefit is summarized in Table 3.

Table 3. Acceptable Periprocedural Death or Stroke Rate in Clinical Trials of CEA
SymptomsStenosis, %Acceptable Periprocedural Death/Stroke Rate, %Anticipated Life Expectancy, y
No60-99<35
Yes50-69<65
70-99<62

CEA: carotid endarterectomy.

As an example of the fine line between benefit and harm, Arazi et al (2008)8, performed a decision analysis of benefit for patients with asymptomatic stenosis using a base case derived from the Asymptomatic Carotid Surgery Trial (periprocedural death/stroke rate, 1.8%).7, Over a five-year time horizon, CEA provided four days of stroke-free survival and a net harm when periprocedural death or disabling stroke rates exceeded 2.1%.

Since the landmark trials, there has been considerable improvement in medical care resulting in a substantial decline in stroke rates among patients with asymptomatic carotid disease.9,10, Current medical therapies such as aggressive lipid-lowering medications, were inconsistently used in the landmark trials. Also, surgeons in contemporary clinical trials have achieved CEA periprocedural death and stroke rates lower than those in the pivotal trials used to establish the benchmarks. For example, in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), the death or stroke rate for symptomatic patients was 3.2% and for asymptomatic patients was 1.4%.11, Accordingly, the benchmarks established decades ago may no longer be appropriate. A recent consensus document by De Rango et al (2013) has suggested benchmarks of 2.0% for asymptomatic and 4.0% for symptomatic individuals.12,

Excluded from landmark CEA trials were patients with significant comorbidities judged likely to cause death within five years that might also increase periprocedural and anesthetic risk for complications. Therefore, CAS has appeal as a treatment option for patients with potentially higher periprocedural risk due to medical (eg, severe cardiac dysfunction, requirement for combined coronary and carotid revascularization, severe renal or pulmonary dysfunction, and other characteristics associated with increased surgical risk), or anatomic reasons (eg, surgically inaccessible stenosis, prior radiation, prior neck surgery, spinal immobility, prior laryngeal nerve palsy, contralateral occlusion, prior ipsilateral CEA, restenosis after CEA).

Although the general anesthetic risk is considered a potential reason to use CAS, CEA can be safely performed under local or regional anesthesia,13, as confirmed in the 95-center General Anesthesia versus Local Anesthesia trial.14,The General Anesthesia versus Local Anesthesia trial investigators randomized 3526 patients undergoing CEA to general or local anesthesia and found no difference in 30-day death, stroke, or myocardial infarction (MI) rates based on anesthetic approach (relative risk [RR], 0.94; 95% confidence interval [CI], 0.70 to 1.3).14,

Randomized Controlled Trials of Carotid Artery Stenting versus Carotid Endarterectomy
SAPPHIRE Trial

The first major RCT comparing CAS with CEA was the Stenting and Angioplasty, with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial reported by Yadav et al (2004).15,The relevant conclusions are summarized below:

    • For patients with symptomatic stenosis at increased risk for periprocedural complications from CEA (n=96), the sample size was small, resulting in wide CIs for estimated effects; differences between arms in 30-day and 1-year outcomes were not statistically significant.
    • For patients with asymptomatic stenosis at increased risk for periprocedural complications from CEA (n=238), differences in 30-day outcomes also had wide CIs and were not statistically significant.
    • Early study closed early due to slow recruitment as nonrandomized stent registries were established, resulting in fewer study patients than planned, which compromised the evaluation of noninferiority.
    • Variance in differential complication rates for the 2 treatments across sites might have influenced results, because 5 of 34 sites contributed 64% of randomized patients, and data were unavailable for comparison.
    • Direct comparative evidence was lacking for optimal medical management alone as an alternative to adding CAS with an embolic protection device (EPD) or CEA for patients with increased risk of surgical complications.
Long-term follow-up of SAPPHIRE was reported at three years.16,17, For asymptomatic and symptomatic patients combined, ipsilateral strokes from day 31 to day 1080 were observed in 4.4% of patients undergoing CAS and in 3.6% with CEA (estimated from digitized figure). Cumulative 3-year repeat target vessel revascularization (a proxy for restenosis) was more common after CEA but the difference was not statistically significant (7.1% vs 3.0%; p=0.26).

SPACE Trial

Ringleb et al (2006) published results from the Stent-supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) trial. This trial randomized 1200 patients within 180 days of neurologic symptoms, transient ischemic attack, or moderate (nondisabling) stroke, and with 50% or more stenosis of the ipsilateral carotid artery, to CAS (n=605) with or without EPD (73% of procedures performed without), or to CEA (n=595).18, The analysis (n=1183) failed to conclude that CAS was noninferior to CEA by a margin of 2.5% for the primary outcome of ipsilateral ischemic stroke or death by 30 days after randomization. Periprocedural (30-day) event rates were 6.8% for the CAS group and 6.3% for the CEA group. The absolute between-group difference favored CEA and was 0.5% (90% CI, -1.9% to 2.9%) by intention-to-treat analysis and 1.3% (90% CI, -1.1% to 3.8%) in per-protocol analysis.

Editorialists pointed to some methodologic issues raised with the SPACE trial, including the high rate of rejection for potential participating collaborators (»25%, based on their prior outcomes records, but review criteria were not reported), and the lack of a requirement to use an EPD with CAS (although 30-day event rates were 7.3% with vs 6.7% without EPD).19,20,

Long-term follow-up of the SPACE trial was reported at two years.17, Approximate annual ipsilateral stroke rates from day 31 through longest follow-up for CAS and CEA were 0.4% in each group. Following the periprocedural period (ie, 31 days to longest follow-up), stroke risk reduction in symptomatic patients not selected based on medical or anatomic comorbidities was similar for CAS and CEA. Recurrent stenosis greater than 70% was more frequent at 2 years with CAS (10.7%) than with CEA (4.6%; p=0.001).

EVA-3S Trial

The Endarterectomy Versus Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial was a noninferiority comparison of CAS (with EPD in 92%) to CEA in symptomatic patients at average risk for complications from CEA with 60% or more stenosis of the ipsilateral carotid artery.21, The trial was terminated prematurely (n=527 enrolled; original target, n=872), based on interim analysis of 30-day outcomes. The incidence of any stroke or death through 30 days was 3.9% (95% CI, 2.0% to 7.2%) after CEA and 9.6% (95% CI, 6.4% to 14%) after CAS (RR=2.5; 95% CI, 1.2 to 5.1; p=0.01).

Over a mean 2.1 years of follow-up, restenosis (≥50%) was more frequent following CAS (12.5%) than CEA (5.0%).22, Long-term follow-up from EVA-3S was reported at four years.23, Approximate annual ipsilateral stroke rates from day 31 through longest follow-up for CAS and CEA, respectively, were 1.1% and 0.9%. These results supported a conclusion that following the periprocedural period (ie, 31 days to longest follow-up), stroke risk reduction in symptomatic patients not selected based on medical or anatomic comorbidities was similar for CAS and CEA.

Editorialists criticized EVA-3S for recommending but not requiring antiplatelet premedication (three days of aspirin plus ticlopidine or clopidogrel) and for not requiring interventionalists to be adequately experienced with the specific stent, and EPDs used to treat trial subjects.19,20, Participating interventionalists were required to have completed 12 or more CAS procedures compared with 25 or more CEAs for vascular surgeons. EVA-3S also permitted the use of five different stents and seven different EPDs but required only two prior procedures with a new device before an investigator could use that device on a patient randomized to CAS.

Mas et al (2014) published long-term follow-up (median, 7.2 years) from the EVA-3S trial.24, Complete follow-up until death or the final telephone interview was obtained in 493 (94%) of the 527 patients. At the 5-year follow-up, the main composite endpoint (ipsilateral stroke after randomization or procedural stroke or death) occurred in 29 (11%) of 265 subjects in the CAS group and 16 (6.1%) of 262 subjects in the CEA group (5-year absolute risk reduction, 4.7%). The hazard ratio (HR) for CAS vs CEA was 1.85 (95% CI, 1.0 to 3.40; p=0.04). At the 10-year follow-up, the HR for the main composite endpoint for CAS vs CEA was 1.70 (95% CI, 0.95 to 3.06; p=0.07).

International Carotid Stenting Study

The International Carotid Stenting Study (ICSS) enrolled 1713 symptomatic patients at 50 academic medical centers across Europe, Australia, New Zealand, and Canada between May 2001 and October 2008.25, EPDs were recommended but not required (used in 72% of procedures), and a number of different stents and EPD types were used. Based on plausible event rates, a target study sample size of 1500 was estimated to be able to define a between-group difference less than 3.3% in disabling stroke or death and a 3.0% difference in 30-day stroke, death, or MI. Only interim 30- and 120-day results were included in the initial report. From a per-protocol analysis, the 7.1% periprocedural death or stroke death rates accompanying CAS both exceeded the rate established to provide a net clinical benefit and was more than twice that following CEA (3.4%). In a subgroup analysis of 231 ICSS participants, new ischemic brain lesions were approximately 3-fold more frequent following CAS, and protective devices did not appear to mitigate their occurrence.26, Interim results were consistent with the accompanying editorialist’s conclusion that “routine stenting in symptomatic patients must now be difficult to justify….”27,

Bonati et al (2015) published longer term follow-up results from ICSS.28, The cumulative 5-year risk of fatal or disabling stroke did not differ significantly between the CAS (6.4%) and the CEA groups (6.5%; HR=1.06; 95% CI, 0.72 to 1.57; p=0.77). However, the 5-year cumulative risk of any stroke was higher in the CAS group (15.2%) than in the CEA group (9.45%; HR=1.71; 95% CI, 1.28 to 2.3; p<0.001). The authors noted that the difference between CEA and CAS groups in stroke risk after the procedural period was mainly attributable to strokes occurring in the contralateral carotid or vertebrobasilar territory in the CAS group. Functional outcomes, measured by modified Rankin Scale scores, did not differ significantly between groups.

Altinbas et al (2014) reported that periprocedural rates of hemodynamic instability in the ICSS differed between CEA and CAS groups.29, Hemodynamic depression occurred more commonly in CAS patients (13.8% vs 7.2%; RR=1.9; 95% CI, 1.4 to 2.6; p<0.000), while hypertension requiring treatment occurred less commonly in CAS patients (RR=0.2; 95% CI, 0.1 to 0.4; p<0.000). Hemodynamic instability was not associated with the ICSS study’s primary composite outcome.

Featherstone et al (2016) published a health technology assessment on ICSS funded by the National Institute for Health Research.30, The assessment reviewed the data presented above, concluding that "the functional outcome after stenting is similar to endarterectomy, but stenting is associated with a small increase in the risk of nondisabling stroke. The choice between stenting and endarterectomy should take into account the procedural risks related to individual patient characteristics."

CREST

CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) was conducted between December 2000 and July 2008, and enrolled 2522 patients at 117 centers across the U. S. and Canada.11, Of 427 interventionalists who applied to participate in CREST, only 224 (52%) were approved.31, Inclusion was initially restricted to recently symptomatic patients. Due to slow enrollment, the protocol was amended to include asymptomatic patients. A March 2004 protocol amendment excluded further enrollment of patients 80 years and older due to poor outcomes. Of the 1271 patients randomized to CAS, 65 underwent CEA and 54 neither procedure; of the 1251 patients randomized to CEA, 13 underwent CAS and 44 neither procedure. Twenty patients were excluded from one site due to reported data fabrication. A sample size of 2500 was targeted to detect a 46% reduction in the HR for the primary endpoint of any stroke, MI, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization.

In the entire sample (symptomatic and asymptomatic patients), investigators reported no difference between CAS and CEA for the primary outcome. Stroke was more frequent following CAS; MI more frequent after CEA. The periprocedural MI rate after CEA (2.3%) was considerably higher in CREST than any comparable trial (eg, in EVA-3S, 0.8%; SPACE, 0%; ICSS, 0.6%). This might be attributable to a somewhat higher prevalence of coronary artery disease among participants and routine cardiac enzyme assays, but the relative difference was large. Periprocedural CAS death or stroke rates were the lowest reported in any trial. Although participating interventionalists performing CAS were highly selected, periprocedural death or stroke rates following CAS exceeded those for CEA: in symptomatic patients, 5.6% vs 2.4%, respectively (the lowest rate for CAS reported in any trial); in asymptomatic patients, 2.6% vs 1.4%, respectively.32, The RR for periprocedural death or stroke in the symptomatic group was 1.89 (95% CI, 1.11 to 3.21) and in the asymptomatic group, it was 1.85 (95% CI, 0.79 to 4.34). The trial had limited power to detect a difference between procedures in the asymptomatic group. In CREST, 2-year restenosis (>70%) or reocclusion rates were similar following CEA (6.3%) and CAS (6.0%) - 2-year restenosis alone was 5.8% with either procedure.33,

Brott et al (2016) reported on long-term follow-up from CREST. There were no significant differences in the primary composite outcome (any periprocedural stroke, MI, death, or postprocedural ipsilateral stroke) between the CEA (9.9%) and CAS (11.8%; HR=1.10) groups when measured out to 10 years.34, The second primary endpoint (postprocedural ipsilateral stroke rates) also did not differ significantly between CEA (5.6%) and CAS (6.9%; HR=0.99).

Interventionalists in CREST were the most carefully selected in any trial, and the lack of similar selection criteria has been a critique of the other trials.35, Analyses of CAS in Medicare patients between 2005 and 2007 found that few CAS operators had the experience of CREST investigators.36, Among the 11846 procedures with documented operator experience, 68% were performed by operators having performed fewer than 12 procedures.

In a follow-up analysis of CREST data, Gonzales et al (2014) reported no differences in efficacy and safety outcomes for subjects based on receiving treatment in high-, medium-, or low-volume centers.37,

Asymptomatic Carotid Trial

The Asymptomatic Carotid Trial I was a noninferiority trial reported by Rosenfield et al (2016) who compared CAS with CEA in asymptomatic individuals, not at high-risk for surgical complications38,.Enrollment began in 2005, with a target of 1658 participants; but, because of slow enrollment, the trial was halted in 2013 at 1453 participants. The primary composite endpoint (death, stroke, or MI within 30 days or ipsilateral stroke within 1 year) was met by 3.8% of CAS and 3.4% of CEA patients, while the cumulative 5-year rate of stroke-free survival was 93.1% with CAS and 94.7% with CEA (p=0.44). This trial did not answer how best to treat asymptomatic patients, because it did not include a medical therapy arm. Patients treated with current best medical therapy might have had an ipsilateral stroke rate of only 0.5% to 1% per year.39,

Additional RCTs

Several other smaller trials have compared CEA with CAS. Li et al (2014) published a trial that randomized 130 subjects at high-risk of stroke due to angiographically confirmed carotid stenosis (≥50%) to CEA (n=65) or CAS (n=65).40, The authors reported a 3-month postoperative risk of mortality of 1.5% with CAS compared with 9.2% with CEA. However, “existence of complete follow-up data” was an inclusion criterion, and insufficient details were provided about enrollment and randomization procedures to permit conclusions about the trial.

Kuliha et al (2015) published results of an RCT that allocated 150 subjects with at least 70% internal carotid artery stenosis to CEA (n=73) or CAS (n=77).41,New infarctions on magnetic resonance imaging were found more frequently after CAS (49% vs 25%; p=0.002).

Reiff et al (2019) published one-year interim results of the Stent-supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy 2 (SPACE-2) RCT.42, The SPACE-2 RCT was originally planned to compare best medical treatment (BMT) to CEA plus BMT or CAS plus BMT in 3550 patients with high grade asymptomatic extracranial carotid artery stenosis. But, because patient recruitment was slow, the RCT was amended in 2013 to become two parallel randomized studies (BMT alone versus CEA plus BMT, and BMT alone versus CAS plus BMT). After recruitment continued to be slow, SPACE-2 was ultimately stopped early in 2016 after only 513 patients were randomized. Although the interim analysis did not find significant differences between CEA and CAS in one-year rates of stroke or all-cause mortality, SPACE-2 authors noted that it is insufficiently powered to detect such differences.

Section Summary: Randomized Controlled Trials of Carotid Artery Stenting versus Carotid Endarterectomy

RCTs comparing CEA with CAS enrolled a mix of symptomatic and asymptomatic patients and employed different selection criteria for participating centers. Periprocedural stroke and death rates following CAS exceeded those after CEA. Following the early perioperative period (≥31 days), the rates of ipsilateral stroke and/or transient ischemic attack appear to be similar for the 2 procedures. While some trials found higher restenosis rates after CAS (SAPPHIRE, SPACE, EVA-3S), restenosis in CREST occurred at similar frequency following either procedure. The rates of early complications in SPACE, EVA-3S, and ICSS exceeded 6.0%. In CREST, periprocedural death or stroke rates with CAS were less than 6% in symptomatic and 3% in asymptomatic patients. Interventionalists in CREST were the most carefully selected in any trial, and the criteria used to credential in other trials has been a focus of criticisms, along with the inconsistent use of EPDs.43,

No RCTs have compared CAS with medical therapy. Therefore, it is not possible to determine whether CAS is superior to medical therapy. Since the pivotal CEA vs medical therapy trials, there has been a marked improvement in medical therapy and declining stroke rates in asymptomatic patients with carotid stenosis. In 1993, the Asymptomatic Carotid Surgery Trial reported that the annual ipsilateral stroke rate was approximately 2.0% with medical therapy.4, A meta-analysis of studies completing enrollment between 2000 and 2010 found a pooled estimate for annual ipsilateral stroke incidence of 1.13%. This decrease in stroke risk has been used to argue that medical therapy in asymptomatic patients is preferable to surgical intervention.27,44,45,

Review of Evidence
Systematic Reviews

Several TEC Assessments and meta-analyses have been published, all reporting similar findings.46,47,48,49,50,51, In average-risk symptomatic patients, the body of evidence has demonstrated worse periprocedural outcomes with CAS than with CEA. While data have shown secular improvement in periprocedural outcomes following CAS, there is evidence of net harm compared with CEA.32,52, A 2010 individual patient data meta-analysis of SPACE, EVA-3S, and ICSS indicated some uncertainty in comparative periprocedural death or stroke rates for younger symptomatic patients.53, Still, that subgroup result must be considered carefully given the larger body of evidence, lack of stratified randomization, as well as the evidence on restenosis. Meta-analyses have generally found that restenosis is more common following CAS than CEA. In a meta-analysis of 13 trials, among those reporting restenosis rates, Bangalore et al (2011) reported pooled relative odds for restenosis following CAS compared with CEA of 2.8 (95% CI, 2.0 to 4.0; I2=0%).49, Of note was the individual patient data meta-analysis (n=3433) of SPACE, EVA-3S, and ICSS.53, In these symptomatic patients, the 30-day death or stroke risk (per-protocol analyses) with CAS was 7.7% vs 4.4% following CEA (RR=1.74; 95% CI, 1.32 to 2.30).

The Carotid Stenting Trialists’ Collaboration (2016) published an individual patient data meta-analysis (total N=4754 patients) of SPACE, EVA-3S, and ICSS data, plus data from symptomatic patients in CREST to evaluate the association between age and risk of stroke or death with CEA and CAS.54, The periprocedural period was defined as 120 days, which is considerably longer than the conventional 30-day periprocedural definition. For symptomatic patients assigned to CEA, there was no increase in the periprocedural or postprocedural risk of death or stroke for patients older than 65 compared with those younger than 60. In contrast, for patients assigned to CAS, the risk of periprocedural events increased with age, from a 2.1% risk for patients less than 60 years, to 11% for patients over 70 years. These analyses found increased periprocedural stroke risk for CAS vs CEA in patients approximately 65 years and older, but not among those younger patients (an age threshold was not defined). Age was not significantly associated with postprocedural stroke risk. The results would suggest that the risk-benefit profile for CAS in symptomatic patients enrolled in these trials could be modified by age, but there was considerable imprecision in the age-specific CAS vs CEA comparisons for periprocedural risk. For example, among patients ages 60 to 64 years, the HR comparing CAS with CEA for the periprocedural risk of stroke or death was 1.07 (95% CI, 0.56 to 2.01). In 2019, on behalf of the Carotid Stenting Trialists’ Collaboration, Brott et al (2019) published another individual patient data meta-analysis of the same symptomatic patient group (total n=4775 patients) from SPACE, EVA-3S, ICSS, and CREST to evaluate long-term outcomes (mean follow-up of 4 years).55, Periprocedural and postprocedural risks continued to favor CEA.

Paraskevas et al (2014) conducted a systematic review of studies comparing cognitive outcomes after CEA with those after CAS.56, Thirteen studies were included, with heterogeneity in the types of cognitive outcome measures reported. In qualitative analysis, reviewers found that most studies did not report a significant difference between CEA and CAS regarding cognitive outcomes and that heterogeneity across outcomes reported precluded more definitive conclusions.

Galyfos et al (2014) reported on results of a meta-analysis that included 9 trials (total n = 5959 patients) with a focus on the risk of periprocedural symptomatic or asymptomatic myocardial ischemia or MI.57, Four trials did not report their definitions for myocardial ischemia, and other studies varied in their definitions. In the pooled analysis, compared with CEA, CAS was associated with decreased risk of cardiac damage (pooled RR=0.37; 95% CI, 0.22 to 0.61; p<0.000). However, reviewers provided incomplete information on the selection of studies for inclusion, which limits conclusions that can be drawn.

Vincent et al (2015) conducted a meta-analysis of 8 RCTs (total n=7091 patients).54, Studies selected compared CAS with CEA, enrolled more than 50 patients, and reported periprocedural or long-term outcomes. Included were the CREST, ICSS, SPACE, EVA-3S, and SAPPHIRE trials (described above), along with the Carotid and Vertebral Artery Transluminal Angioplasty Study, an RCT comparing surgical management with endovascular treatment in 504 patients with symptomatic carotid stenosis. CAS was associated with an increased risk of any periprocedural stroke (RR=1.49; 95% CI, 1.11 to 2.01), a similar risk of a disabling or major stroke, and a decreased risk of periprocedural MI (RR=0.47; 95% CI, 0.29 to 0.78) compared with CEA. However, in long-term follow-up (range, 2-10 years), stenting was associated with an increased risk of stroke (RR=1.36; 95% CI, 1.16 to 1.61) and an increased risk of the composite endpoint of ipsilateral stroke, periprocedural stroke, or periprocedural death (RR=1.45; 95% CI, 1.20 to 1.75) compared with CEA. This analysis supported a conclusion that CEA remains the treatment of choice for most patients due to the increase in adverse events with CAS.

Section Summary: Systematic Reviews

The systematic reviews have corroborated the results of individual RCTs that early adverse events are higher with CAS than with CEA, that long-term stroke rates following the perioperative period are similar, and that restenosis rates are higher with CAS. These data would indicate that, for the average-risk patient with carotid stenosis, CAS is associated with net harm compared with CEA.

Periprocedural Death or Stroke Rates Following Carotid Artery Stenting
Systematic Reviews

Questions of periprocedural death or stroke rates were assessed in a TEC Assessment (2010).58, Given that CAS (like CEA) trades the procedure-related risks of stroke and death for a reduced risk of stroke over subsequent years, and limits for periprocedural stroke and death rates that can be assumed to achieve a net clinical benefit outlined in current guidelines are less than 3% for asymptomatic and less than 6% for symptomatic patients, the Assessment sought evidence to address two questions: (1) Is the periprocedural rate of death or stroke with CAS less than 3% for asymptomatic and less than 6% for symptomatic patients? (2) For those subgroups defined by (a) medical comorbidities or (b) unfavorable anatomy, are periprocedural rates of death or stroke with CAS less than 3% for asymptomatic and less than 6% for symptomatic patients?

To the first question, the Assessment identified 18 multicenter prospective registries collectively enrolling 20194 patients. Eleven of those registries enrolled patients in accordance with the U.S. Food and Drug Administration labeling and with 30-day outcomes available for analysis by symptomatic status (13783 asymptomatic, 3353 symptomatic). In 9 of those registries, 30-day death or stroke rates were either reported or obtained from investigators and in the remaining 2, death or stroke rates were estimated from 30-day death/stroke/MI and MI rates. An independent assessment of neurologic outcomes was required in all but one registry. For asymptomatic patients, the pooled periprocedural death or stroke rate was 3.9% (95% CI, 3.3% to 4.4%; I2=57%); for symptomatic patients, it was 7.4% (95% CI, 6.0% to 9.0%; I2=59%).

A subsequent systematic review, without consideration to the Food and Drug Administration labeling, reported results consistent with the TEC Assessment (pooled periprocedural death/stroke rates in asymptomatic patients of 3.3% [95% CI, 2.6% to 4.1%; 23 studies; n=8504 patients] and in symptomatic patients of 7.6% [95% CI, 6.3% to 9.1%; 42 studies; n=4910 patients]).52,

To the second question, the Assessment found that combined data from 2 registries reported periprocedural death or stroke rates for patients with unfavorable anatomy59,60, but included only 371 asymptomatic (30-day death or stroke rate, 2.7%; 95% CI, 1.5% to 4.9%) and 60 symptomatic patients (30-day death or stroke rate, 1.7%; 95% CI, 0.3% to 8.9%). No other registry reported results by symptomatic status for those subgroups.

Since of the 2010 TEC Assessment, additional evidence has been published on rates of periprocedural stroke and death following CAS, particularly for subgroups defined by medical comorbidities. Spangler et al (2014) evaluated patients treated with isolated primary CEA (n=11336) or primary CAS (n=544) at 29 centers between 2003 and 2013 to assess periprocedural mortality and stroke risks for those considered at medically high-risk.61, A Cox proportional hazards model was used to generate predicted five-year mortality, and patients in the highest risk score quartile were considered high-risk. For asymptomatic patients, there were no significant differences between CEA and CAS for major periprocedural outcomes (major or minor stroke, MI, death) for either high- or low-risk patients. Periprocedural death or stroke rates with CAS were 1.1% for low-risk patients and 1.6% for high-risk patients. For symptomatic patients, periprocedural death or stroke rates were higher with CAS than with CEA for both low- and high-risk groups. For low-risk symptomatic patients, periprocedural death or stroke rates were 6.0% for CAS and 2.2% for CEA (p<0.01). For high-risk symptomatic patients, periprocedural death or stroke rates were 9.3% for CAS and 2.5% for CEA (p<0.01).

Retrospective Analyses

Salzler et al (2017) conducted a large retrospective analysis of the increased use of CAS since the Centers for Medicare & Medicaid guidelines recommended CAS for high-risk patients needing carotid revascularization.62, Data from the Nationwide Inpatient Sample were searched for patients undergoing carotid revascularization. From 2005 (when the guidelines were published) to 2011, 20079 CEAs and 3447 CASs were performed on high-risk patients. During the study period, CAS utilization increased significantly among all high-risk patients. A subgroup analysis of symptomatic high-risk patients did not show an increase in CAS use, indicating that the increase in CAS was primarily in asymptomatic high-risk patients. The odds of in-hospital mortality (odds ratio, 2.6; 95% CI, 1.2 to 5.6) and postoperative in-hospital stroke (odds ratio, 1.5; 95% CI, 1.1 to 3.7) were independently and significantly higher in patients undergoing CAS compared with CEA in the overall sample of high-risk patients.

Carotid Artery Stenting for Carotid Dissection

Carotid dissection is uncommon (incidence »2 per 100000/year) and generally occurs in younger individuals.63, With a frequently favorable prognosis, conservative therapy with anticoagulants to restore blood flow is typically employed while surgical intervention is reserved for patients whose symptoms fail to respond to conservative care. Some have described CAS as a potential treatment in those instances64,65,66,; however, there are no clinical trials comparing alternative strategies and interventions. Current guidelines (detailed below) rate CAS for this indication as a class IIb (level of evidence: C) recommendation.

Summary of Evidence

For individuals who have carotid artery stenosis who receive carotid artery stenting (CAS), the evidence includes randomized controlled trials and systematic reviews of these trials. Relevant outcomes are overall survival, morbid events, and treatment-related mortality and morbidity. A substantial body of randomized controlled trial evidence has compared outcomes of CAS with CEA for symptomatic and asymptomatic patients with carotid stenosis. The evidence does not support the use of CAS in carotid artery disease for the average-risk patient because early adverse events are higher with CAS and long-term outcomes are similar between the two procedures. Data from randomized controlled trials and large database studies have established that the risk of death or stroke with CAS exceeds the threshold considered acceptable to indicate overall benefit from the procedure. Therefore, for patients with carotid stenosis who are suitable candidates for CEA, CAS does not improve health outcomes. The evidence is sufficient to determine that the technology is unlikely to improve the net health outcome.

SUPPLEMENTAL INFORMATION
Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 4 physician specialty societies (6 reviewers) and 4 academic medical centers while this policy was under review in 2009. (Also, an unsolicited response from a specialty society was received.) Input strongly supported the use of carotid artery stenting (CAS) in recently symptomatic patients where surgical carotid endarterectomy cannot be performed due to anatomic reasons, although acknowledging the limited evidence about this subgroup. The lack of alternative treatments for recently symptomatic patients and the established increased risk of stroke were factors supporting this opinion.

Practice Guidelines and Position Statements
American Stroke Association

The American Stroke Association (2011), with 13 other medical societies, issued guidelines on the management of extracranial carotid and vertebral artery diseases, which are summarized in Table 4.67,68,69,

Table 4. Guidelines for Managing Patients With Extracranial Carotid and Vertebral Artery Disease
RecommendationCORaLOEb
CAS is indicated as an alternative to CEA for symptomatic patients at average or low-risk of complications associated with endovascular intervention when the diameter of the lumen of the internal carotid artery is reduced by >70%, as documented by noninvasive imaging or >50% as documented by catheter angiography and the anticipated rate of periprocedural stroke or mortality is <6% (360)IB
Selection of asymptomatic patients for carotid revascularization should be guided by an assessment of comorbid conditions, life expectancy, and other individual factors and should include a thorough discussion of the risks and benefits of the procedure with an understanding of patient preferencesIC
It is reasonable to choose CEA over CAS when revascularization is indicated in older patients, particularly when arterial pathoanatomy is unfavorable for endovascular interventionIIaB
It is reasonable to choose CAS over CEA when revascularization is indicated in patients with neck anatomy unfavorable for arterial surgeryIIaB
When revascularization is indicated for patients with TIA or stroke and there are no contraindications to early revascularization, intervention within 2 wk of the index event is reasonable rather than delaying surgeryIIaB
Prophylactic CAS might be considered in highly selected patients with asymptomatic carotid stenosis (minimum 60% by angiography, 70% by validated Doppler ultrasound), but its effectiveness compared with medical therapy alone in this situation is not well establishedIIbB
In symptomatic or asymptomatic patients at high-risk of complications for carotid revascularization by either CEA or CAS because of comorbidities, the effectiveness of revascularization versus medical therapy alone is not well establishedIIbB
Carotid angioplasty and stenting might be considered when ischemic neurologic symptoms have not responded to antithrombotic therapy after acute carotid dissectionIIbC
Except in extraordinary circumstances, carotid revascularization by either CEA or CAS is not recommended when atherosclerosis narrows the lumen by <50%IIIA
Carotid revascularization is not recommended for patients with chronic total occlusion of the targeted carotid arteryIIIC
Carotid revascularization is not recommended for patients with severe disability caused by cerebral infarction that precludes preservation of useful functionIIIC

CAS: carotid artery angioplasty with stenting; CEA: carotid endarterectomy; COR: class of recommendation; LOE: level of evidence; TIA; transient ischemic attack.


    a
    Class I: benefit >>> risk; class IIa benefit >> risk; class IIb benefit ≥ risk; class III: no benefit.
    b
    Level A (data derived from multiple randomized controlled trials or meta-analyses; multiple populations evaluated); level B (data derived from a single randomized controlled trial or nonrandomized studies; limited populations evaluated); level C (only consensus opinion of experts, case studies, or standard of care; very limited populations evaluated).

Society for Vascular Surgery

The Society for Vascular Surgery (2011) updated its guidelines on the management of the extracranial carotid disease.70, Recommendations from the guidelines are summarized in Table 5.

Table 5. Guidelines for Managing Extracranial Carotid Disease
RecommendationGOEaLOEb
In most patients with carotid stenosis who are candidates for intervention, CEA is preferred to CAS for reduction of all-cause and periprocedural deathIB
CAS is preferred over CEA in symptomatic patients with >50% stenosis and tracheal stoma, situations where local tissues are scarred and fibrotic from prior ipsilateral surgery or external beam radiotherapy, prior cranial nerve injury, and lesions that extend proximal to the clavicle or distal to the C2 vertebral bodyIIB
CAS is preferred over CEA in symptomatic patients with >50% stenosis and severe uncorrectable coronary artery disease, congestive heart failure, or chronic obstructive pulmonary diseaseIIC
There are insufficient data to recommend CAS as primary therapy for neurologically asymptomatic patients with 70%-99% diameter stenosis. In properly selected asymptomatic patients, CAS is equivalent to CEA in the hands of experienced interventionalists with a combined stroke and death rate <3%IIB

CAS: carotid artery angioplasty with stenting; CEA: carotid endarterectomy; GOE: grade of evidence; LOE: level of evidence.


    a
    Grade I: benefit clearly outweighs risk; grade II: benefits and risks are more closely matched and are more dependent on specific clinical scenarios.
    b
    Level B (moderate quality); level C (low quality).

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this policy are listed in Table 6. There are no ongoing or direct comparisons of CAS with CEA in patients at increased risk for CEA complications.72,73, Particularly problematic is the lack of adequate data, from either randomized or nonrandomized studies, to separately compare outcomes of the alternatives (CAS vs CEA vs current optimal medical management) in symptomatic and asymptomatic increased-risk subgroups.

Table 6. Summary of Key Trials
NCT No.Trial NamePlanned EnrollmentCompletion Date
Ongoing
NCT02538276Carotid Endarterectomy and Carotid Artery Stenting in Brazil500Jul 2019 (Unknown status)
NCT00883402Asymptomatic Carotid Surgery Trial-2 (ACST-2): an International Randomised Trial to Compare Carotid Endarterectomy With Carotid Artery Stenting to Prevent Stroke3600Dec 2019
ISRCTN78592017Stent-protected angioplasty in asymptomatic carotid artery stenosis vs endarterectomy: two two-arm clinical trials (SPACE-2)5000Jul 2020
NCT02089217Carotid revascularization and medical management for asymptomatic carotid stenosis trial (CREST-2)2480Dec 2020
ISRCTN97744893European Carotid Surgery Trial 2 (ECST-2): a randomized controlled trial2000Mar 2022

ISRCTN: International Standard Randomized Controlled Trial Number; NCT: national clinical trial.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Extracranial Carotid Artery Stenting
Extracranial Carotid Artery Angioplasty/Stenting with Embolic Protection
ACCULINK Carotid Stent System
ACCUNET
ANGIOGUARD XP
Carotid Artery Stenting
Embolic Protection System
Emboshield
Endotex NexStent
FilterWire EZ
NexStent
Precise Nitinol Carotid Stent System
ProtegeRX
RX ACCULINK Carotid Stent System
RX ACCUNET EPS
SpideRx
Xact RX Carotid Stent System
RX Acculink Carotid Stent System
Carotid Wallstent
GORE Flow Reversal System
GORE Embolic Filter
Mo.Ma Ultra Proximal Cerebral Protection Device

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37. Gonzales NR, Demaerschalk BM, Voeks JH, et al. Complication rates and center enrollment volume in the carotid revascularization endarterectomy versus stenting trial. Stroke. Nov 2014; 45(11): 3320-4. PMID 25256180

38. Rosenfield K, Matsumura JS, Chaturvedi S, et al. Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. N Engl J Med. Mar 17 2016; 374(11): 1011-20. PMID 26886419

39. Spence JD, Naylor AR. Endarterectomy, Stenting, or Neither for Asymptomatic Carotid-Artery Stenosis. N Engl J Med. Mar 17 2016; 374(11): 1087-8. PMID 26890473

40. Li FM, Zhong JX, Jiang X, et al. Therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis. Int J Clin Exp Med. 2014; 7(9): 2895-900. PMID 25356155

41. Kuliha M, Roubec M, Prochazka V, et al. Randomized clinical trial comparing neurological outcomes after carotid endarterectomy or stenting. Br J Surg. Feb 2015; 102(3): 194-201. PMID 25511816

42. Reiff T, Eckstein HH, Mansmann U, et al. Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2. Int J Stroke. Mar 15 2019: 1747493019833017. PMID 30873912

43. Gray WA. Carotid stenting or carotid surgery in average surgical-risk patients: interpreting the conflicting clinical trial data. Prog Cardiovasc Dis. Jul-Aug 2011; 54(1): 14-21. PMID 21722782

44. Woo K, Garg J, Hye RJ, et al. Contemporary results of carotid endarterectomy for asymptomatic carotid stenosis. Stroke. May 2010; 41(5): 975-9. PMID 20339122

45. Barnett HJ, Pelz DM, Lownie SP. Reflections by contrarians on the post-CREST evaluation of carotid stenting for stroke prevention. Int J Stroke. Dec 2010; 5(6): 455-6. PMID 21050401

46. Muller MD, Lyrer P, Brown MM, et al. Carotid artery stenting versus endarterectomy for treatment of carotid artery stenosis. Cochrane Database Syst Rev. Feb 25 2020; 2: CD000515. PMID 32096559

47. . Angioplasty and stenting of the cervical carotid artery with distal embolic protection of the cerebral circulation. Technol Eval Cent Assess Program Exec Summ. Feb 2005; 19(15): 1-4. PMID 15714698

48. Ederle J, Featherstone RL, Brown MM. Randomized controlled trials comparing endarterectomy and endovascular treatment for carotid artery stenosis: a Cochrane systematic review. Stroke. Apr 2009; 40(4): 1373-80. PMID 19228850

49. Bangalore S, Kumar S, Wetterslev J, et al. Carotid artery stenting vs carotid endarterectomy: meta-analysis and diversity-adjusted trial sequential analysis of randomized trials. Arch Neurol. Feb 2011;68(2):172-184. PMID

50. Murad MH, Shahrour A, Shah ND, et al. A systematic review and meta-analysis of randomized trials of carotid endarterectomy vs stenting. J Vasc Surg. Mar 2011; 53(3): 792-7. PMID 21216556

51. Economopoulos KP, Sergentanis TN, Tsivgoulis G, et al. Carotid artery stenting versus carotid endarterectomy: a comprehensive meta-analysis of short-term and long-term outcomes. Stroke. Mar 2011; 42(3): 687-92. PMID 21233476

52. Touze E, Trinquart L, Chatellier G, et al. Systematic review of the perioperative risks of stroke or death after carotid angioplasty and stenting. Stroke. Dec 2009; 40(12): e683-93. PMID 19892997

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54. Vincent S, Eberg M, Eisenberg MJ, et al. Meta-Analysis of Randomized Controlled Trials Comparing the Long-Term Outcomes of Carotid Artery Stenting Versus Endarterectomy. Circ Cardiovasc Qual Outcomes. Oct 2015; 8(6 Suppl 3): S99-108. PMID 26515216

55. Brott TG, Calvet D, Howard G, et al. Long-term outcomes of stenting and endarterectomy for symptomatic carotid stenosis: a preplanned pooled analysis of individual patient data. Lancet Neurol. Apr 2019; 18(4): 348-356. PMID 30738706

56. Paraskevas KI, Lazaridis C, Andrews CM, et al. Comparison of cognitive function after carotid artery stenting versus carotid endarterectomy. Eur J Vasc Endovasc Surg. Mar 2014; 47(3): 221-31. PMID 24393665

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60. White CJ, Iyer SS, Hopkins LN, et al. Carotid stenting with distal protection in high surgical risk patients: the BEACH trial 30 day results. Catheter Cardiovasc Interv. Apr 2006; 67(4): 503-12. PMID 16548004

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62. Salzler GG, Farber A, Rybin DV, et al. The association of Carotid Revascularization Endarterectomy versus Stent Trial (CREST) and Centers for Medicare and Medicaid Services Carotid Guideline Publication on utilization and outcomes of carotid stenting among high-risk patients. J Vasc Surg. Jul 2017; 66(1): 104-111.e1. PMID 28502543

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Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*
    37215
    37216
    37217
HCPCS

* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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