Medical Policies - Surgery
Extracranial Carotid Angioplasty or Stenting
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Carotid angioplasty with associated stenting and embolic protection may be considered medically necessary in patients with:
• 50-99% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] measurement); AND
• Symptoms of focal cerebral ischemia (transient ischemic attack [TIA] or monocular blindness) in previous 120 days, symptom duration less than 24 hours, or nondisabling stroke; AND
• Anatomic contraindication for carotid endarterectomy (CEA), such as prior radiation treatment or neck surgery, lesions surgically inaccessible, spinal immobility, or tracheostomy.
Carotid angioplasty with or without associated stenting and embolic protection is considered experimental, investigational and/or unproven for all other indications, including but not limited to:
• Patients with carotid stenosis who are suitable candidates for CEA,
• Patients with carotid artery dissection, and
• Patients who are not considered high-risk and are asymptomatic.
Carotid artery angioplasty with stenting is a treatment for carotid stenosis that is intended to prevent future stroke. It is an alternative to medical therapy and a less-invasive alternative to carotid endarterectomy (CEA).
When an angioplasty is performed, a small balloon at the end of a catheter is inflated in the blood vessel at the blocked area. The balloon pushes against the build-up of plaque and compresses or flattens it. At the same time the balloon widens the blood vessel, the blocked vessel opens up and restores blood flow. If a stent is used, it expands to the size and shape of the artery wall, designed to open the artery, restore blood flow and prevent future blockages.
Combined with optimal medical management, carotid angioplasty with or without stenting has been evaluated as an alternative to 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.
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.
A number of carotid artery stents and EPDs have been approved by the U.S. Food and Drug Administration (FDA) through the premarket approval or the 510(k) process. Examples are provided in Table 1.
Table 1. FDA-Approved Carotid Artery Stents and Embolic Protection Devices
Stents and Devices
Guidant, now Abbott Vascular
Acculink™ and RX Acculink™ carotid stents
Guidant, now Abbott Vascular
Accunet™ and RX Accunet™ cerebral protection filters
Xact® RX carotid stent system
Emboshield® embolic protection system
Precise® nitinol carotid stent system
AngioGuard™ XP and RX emboli capture guidewire systems
Endotex Interventional Systems
NexStent® carotid stent over-the-wire and monorail delivery systems
FilterWire EZ™ embolic protection system
ev3 Inc, Arterial Evolution Technology
ProtégéRx® and SpideRx®
GORE® Flow Reversal System
GORE® Embolic Filter
Mo.MA® Ultra Proximal Cerebral Protection Device
Silk Road Medical
ENROUTE™ Transcarotid Stent System and ENROUTE Transcarotid Neuroprotection System
FDA: U.S. 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 (CT) angiography (CTA) 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 Acculink™ 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 (RX) 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 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 (e.g., straight or tapered) and sizes (diameters and lengths) to match the vessel lumen that will receive the stent.
In February 2015, the ENROUTE™ Transcarotid NPS was cleared for marketing by FDA through the 510(k) process. The ENROUTE™ is a flow-reversal device designed to be placed via direct carotid access.
FDA product code: NIM (stents) and NTE (EPDs).
This policy was created in 1993 and updated periodically with literature review. The last update with literature review covers the period through July 2017.
Assessment of efficacy for therapeutic intervention involves a determination of whether the intervention improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes, but are prone to biases such as noncomparability of treatment groups, placebo effect, and variable natural history of the condition.
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.
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. (1-7) Those trial results defined the magnitude of risk reduction for stroke and the periprocedural stroke and death rates that must be offset to achieve a net clinical benefit (benefit outweighing harm)--30-day rates 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 was defined by the trial duration needed to demonstrate benefit--2 years for symptomatic patients with 70% to 99% stenosis, 5 years for symptomatic patients with 50% to 69% stenosis, and asymptomatic patients with greater than 60% stenosis (summarized in Table 2).
Table 2. Acceptable Periprocedural Death/Stroke Rate in Clinical Trials of CEA
Acceptable Periprocedural Death/Stoke Rate shown in %
Anticipated Life Expectancy by # of years
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 (ACST) (periprocedural death/stroke rate, 1.8%).7 Over a 5-year time horizon, CEA provided 4 days of stroke-free survival and a net harm when periprocedural death or disabling stroke rates exceeded 2.1%.
Since the landmark trials were performed, there has been considerable improvement in medical care and evidence of substantial decline in stroke rates with medical care in asymptomatic carotid disease. (9, 10) Current medical therapies including aggressive lipid lowering were inconsistently used in the landmark trials. While indirect, evidence for impact of improved medical care supports a perspective that guidelines for periprocedural death or stroke exceed those needed to obtain a net clinical benefit. Surgeons in contemporary clinical trials have also achieved CEA periprocedural death and stroke rates lower than those in pivotal trials. For example, in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), (11) the death or stroke rate for symptomatic patients was 3.2% and for asymptomatic patients was 1.4%. Accordingly, the benchmarks established decades ago may no longer be appropriate. A recent consensus document (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 5 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 or anatomic reasons (e.g., medical factors include severe cardiac dysfunction, requirement for combined coronary and carotid revascularization, severe renal or pulmonary dysfunction, and other characteristics associated with increased surgical risk; anatomic factors include surgically inaccessible stenosis, prior radiation, prior neck surgery, spinal immobility, prior laryngeal nerve palsy, contralateral occlusion, prior ipsilateral CEA, restenosis after CEA).
Although general anesthetic risk is considered a potential reason to use CAS, CEA can typically be safely performed under local or regional anesthesia, (13) as confirmed in the 95-center General Anesthesia versus Local Anesthesia (GALA) trial. (14) 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 according to anesthetic approach (relative risk [RR], 0.94; 95% confidence interval [CI], 0.70 to 1.3). (14)
RCTs of CAS versus CEA
The first major RCT comparing CAS with CEA was the Stenting and Angioplasty, with Protection in Patients at HIgh Risk for Endarterectomy (SAPPHIRE) trial. (15) The relevant conclusions are summarized as follows:
• SAPPHIRE included few patients with symptomatic stenosis at increased risk for periprocedural complications from CEA (n=96), which resulted in wide confidence intervals 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, differences in 30-day outcomes also had wide confidence intervals and were not statistically significant.
• Early study closure resulted in fewer study patients than planned, which compromised the evaluation of non-inferiority.
• Variance in differential complication rates for the 2 treatments across sites may 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 embolic protection device (EPD) or CEA for patients with increased risk of surgical complications.
Long-term follow-up of SAPPHIRE was reported at 3 years. (16, 17) For asymptomatic and symptomatic patients combined, ipsilateral strokes from day 31 to 1080 days 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% versus 3.0%; p=0.26).
In 2006, results of the Stent-supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) trial were published. This trial randomized 1200 patients within 180 days of neurologic symptoms, transient ischemic attack (TIA), 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 SPACE, 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 of an EPD with CAS (although 30-day event rates were 7.3% with versus 6.7% without EPD). (19, 20)
Long-term follow-up of the SPACE trial was reported at 2 years. (17) Approximate annual ipsilateral stroke rates from day 31 through longest follow-up for CAS and CEA, respectively, were 0.4% in each group. These results supported a conclusion that, following the periprocedural period (i.e., 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 2 years with CAS (10.7%) than with CEA (4.6%; p=0.001).
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 after CEA (5.0%). (22) Long-term follow-up from EVA-3S was reported at 4 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 (i.e., 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 (3 days of aspirin plus either 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 successfully completed 12 or more CAS procedures compared with 25 or more CEAs for vascular surgeons. EVA-3S also permitted use of 5 different stents and 7 different EPDs but required only 2 prior procedures with a new device before an investigator could use that device on a patient randomized to CAS.
In 2014, Mas et al. 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 versus 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 versus CEA was 1.70 (95% CI, 0.95 to 3.06; p=0.07).
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 exceed the rate established to provide a net clinical benefit and was more than twice that following CEA (3.4%). In a substudy 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)
In 2015, Bonati et al. 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). 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.
In 2014, Altinbas et al. 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% versus 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.
In 2016, Featherstone et al. published a health technology assessment (HTA) on ICSS funded by the U.K.’s National Institute for Health Research. (30) The HTA 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 non-disabling stroke. The choice between stenting and endarterectomy should take into account the procedural risks related to individual patient characteristics.”
The CREST was conducted between December 2000 and July 2008, and enrolled 2522 patients at 117 centers across the United States 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 1 site due to reported data fabrication. A sample size of 2500 was targeted to detect a 46% reduction in the hazard ratio 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 (e.g., 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% versus 2.4%, respectively (the lowest rate for CAS reported in any trial); in asymptomatic patients, 2.6% versus 1.4%, respectively. (32) The relative risk 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)
In 2016, Brott et al. 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 11,846 procedures with documented operator experience, 68% were performed by operators having performed fewer than 12 procedures.
In a follow-up analysis of CREST data, Gonzalez et al. (2014) reported no differences in outcomes for subjects treated in high-, medium-, or low-volume centers. (37)
The Asymptomatic Carotid Trial (ACT) I was a noninferiority trial comparing CAS to CEA in asymptomatic individuals not at high-risk for surgical complications. (38) 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 does 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)
Several other smaller trials have compared CEA with CAS. In 2014, Li et al. published a study that randomized 130 subjects at high-risk of stroke due to angiographically confirmed carotid stenosis (≥50%) to CEA (n=65) or to 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 to be drawn about the study.
In 2015, Kuliha et al. published results of an RCT that allocated 150 subjects with at least 70% internal carotid artery stenosis to CEA (n=73) or to CAS (n=77). (41) New infarctions on magnetic resonance imaging (MRI) were found more frequently after CAS (49% vs 25%; p=0.002).
Section Summary: RCTs of CAS versus CEA
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, the subsequent rates of ipsilateral stroke and/or TIA 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. (42) The ACT I trial reported was unable to treat asymptomatic patients as the trial methods were not set up with a medical arm (38)
No RCTs have compared CAS with medical therapy. Since the pivotal CEA versus medical therapy trials, there has been marked improvement in medical therapy and declining stroke rates in asymptomatic patients with carotid stenosis. In 1993, the Asymptomatic Carotid Artery Stenosis trial (4) reported that the annual ipsilateral stroke rate was approximately 2.0% with medical therapy. (10) 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 intervention. (27, 43, 44) Therefore, it is not possible to determine whether CAS is superior to medical therapy.
Systematic Reviews and Meta-Analysis
Several Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessments and meta-analyses have been published, all reporting with similar findings. (45-49) 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 a net harm compared with CEA. (32, 50) A 2010 individual patient data (IPD) meta-analysis of SPACE, EVA-3S, and ICSS indicated some uncertainty in comparative periprocedural death or stroke rates for younger symptomatic patients. (51) 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%). (47) Of note was the IPD meta-analysis (N=3433) of SPACE, EVA-3S and ICSS. (51) In these symptomatic patients, the 30-day death or stroke risk (per-protocol analyses) with CAS was 7.7% versus 4.4% following CEA (RR=1.74; 95% CI, 1.32 to 2.30).
In 2016, the Carotid Stenting Trialists’ Collaboration published an IPD meta-analysis (N=4754) 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. (52) 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 periprocedural or postprocedural risk of death or stroke for patients older than 65 compared to patients 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 younger than 60 years, to 11% for patients older than 70 years. These analyses found increased periprocedural stroke risk for CAS versus CEA in patients approximately 65 years of age 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 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 versus CEA comparisons for periprocedural risk. For example, among patients aged 60 to 64 years, the hazard ratio comparing CAS to CEA for the periprocedural risk of stroke or death was 1.07 (95% CI, 0.56 to 2.01).
Paraskevas et al. (2014) conducted a systematic review of studies comparing cognitive outcomes after CEA with those after CAS. (53) Thirteen studies were included, with heterogeneity in the types of cognitive outcome measures reported. In qualitative analysis, reviewers reported that most studies did not report a significant difference between CEA and CAS in terms of cognitive outcomes and that heterogeneity across outcomes reported precluded more definitive conclusions.
Galyfos et al. (2014) reported results of a systematic review that included 9 trials (total N=5959 patients) with a focus on risk of periprocedural symptomatic or asymptomatic myocardial ischemia or MI. (54) Four trials did not report their definitions for myocardial ischemia, and other studies varied in their definitions. In pooled analysis, compared with CEA, CAS was associated with decreased risk for cardiac damage (pooled RR=0.37; 95% CI, 0.22 to 0.61; p<0.000). However, the review provided incomplete information on selection of studies for inclusion, which limits conclusions that can be drawn.
In 2015, Vincent et al. conducted a meta-analysis of 8 RCTs (total N=7091 patients). (55) Studies selected compared CAS to 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 CAVATAS, an RCT comparing surgical management with endovascular treatment in 504 patients with symptomatic carotid stenosis. CAS was associated with an increased risk of any type of 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). However, in 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 end-point of ipsilateral stroke, periprocedural stroke, or periprocedural death (RR=1.45; 95% CI, 1.20 to 1.75). This analysis supports the conclusion that CEA remains the treatment of choice for most patients due to the increase in adverse events with CAS.
Section Summary: Systematic Reviews and Meta-Analysis
The systematic reviews have corroborated the results of individual RCTs that early adverse events are higher with CAS compared with CEA, that long-term stroke rates following the perioperative period are similar, and that restenosis rates are higher with CAS. These data indicate that, for the average-risk patient with carotid stenosis, CAS is associated with a net harm compared with CEA.
Periprocedural Death or Stroke Rates Following CAS
Questions of periprocedural death or stroke rates were assessed in the 2010 BCBSA TEC Assessment. (56) Noting again 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 traded 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 2 questions:
1. Is the periprocedural death/stroke rate 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 death/stroke rates with CAS less than 3% for asymptomatic and less than 6% for symptomatic patients?
To the first question, the TEC Assessment identified 18 multicenter prospective registries collectively enrolling 20,194 patients; 11 enrolled patients in accordance with U.S. Food and Drug Administration (FDA) labeling and with 30-day outcomes available for analysis by symptomatic status (13,783 asymptomatic, 3353 symptomatic). For 9 registries, 30-day death or stroke rates were either reported or obtained from investigators; 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 1 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 FDA 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; 4910 patients]). (50)
To the second question, the TEC Assessment found that combined data from 2 registries reported periprocedural death or stroke rates for patients with unfavorable anatomy (57, 58) but included only 371 asymptomatic (30-day death/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 the publication of the 2010 TEC Assessment, additional evidence has been published related to 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=11,336) or primary CAS (n=544) at 29 centers between 2003 and 2013 to assess periprocedural mortality and stroke risks for patients considered at medically high-risk. (59) A Cox proportional hazards model was used to generate predicted 5-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).
CAS for Carotid Dissection
Carotid dissection is uncommon (incidence »2 per 100,000/year) and occurs generally in younger individuals. (60) 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 instances (61-63); however, there are no clinical trials comparing alternative strategies and interventions. Current guidelines (detailed next) rate CAS for this indication as a class IIb (level of evidence: C) recommendation.
Clinical Input Received through Physician Specialty Societies and Academic Medical Centers
BCBSA requested and received input through 4 Physician Specialty Societies and 4 Academic Medical Centers while their policy was under review in 2009. This clinical input strongly supported use of CAS in recently symptomatic patients where CEA cannot be performed due to anatomic reasons, although acknowledging the limited evidence pertaining to this subgroup. The lack of alternative treatments for recently symptomatic patients and the established increased risk of stroke were factors supporting this opinion.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 3. There are no ongoing or direct comparisons of CAS with CEA in patients at increased risk for CEA complications. (64) Particularly problematic is the lack of adequate data, from either randomized or nonrandomized studies, to separately compare outcomes of the alternatives (CAS versus CEA versus current optimal medical management) in symptomatic and asymptomatic increased risk subgroups.
Table 3. Summary of Key Trials
Asymptomatic Carotid Surgery Trial-2 (ACST-2): An International Randomized Trial to Compare Carotid Endarterectomy with Carotid Artery Stenting to Prevent Stroke
Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis versus Endarterectomy: Two Two-Arm Clinical Trials (SPACE-2)
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2)
European Carotid Surgery Trial 2 (ECST-2): A Randomized Controlled Trial
NCT: National Clinical Trial.
Practice Guidelines and Position Statements
American Stroke Association (ASA)
In 2011, the ASA, with 13 other medical societies, issued guidelines on the management of extracranial carotid and vertebral artery diseases, which are summarized in Table 4. (65-67)
Table 4. Guidelines on the Management of Patients with Extracranial Carotid and Vertebral Artery Disease
Level of Evidenceb
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 more than 70% as documented by noninvasive imaging or more than 50% as documented by catheter angiography and the anticipated rate of periprocedural stroke or mortality is less than 6%.
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 preferences.
It is reasonable to choose CEA over CAS when revascularization is indicated in older patients, particularly when arterial pathoanatomy is unfavorable for endovascular intervention.
It is reasonable to choose CAS over CEA when revascularization is indicated in patients with neck anatomy unfavorable for arterial surgery.
When revascularization is indicated for patients with TIA or stroke and there are no contraindications to early revascularization, intervention within two weeks of the index event is reasonable rather than delaying surgery.
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 established.
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 established.
Carotid angioplasty and stenting might be considered when ischemic neurological symptoms have not responded to antithrombotic therapy after acute carotid dissection.
Except in extraordinary circumstances, carotid revascularization by either CEA or CAS is not recommended when atherosclerosis narrows the lumen by less than 50%.
Carotid revascularization is not recommended for patients with chronic total occlusion of the targeted carotid artery.
Carotid revascularization is not recommended for patients with severe disability caused by cerebral infarction that precludes preservation of useful function.
CAS: carotid artery stenting;
CEA: carotid endarterectomy.
Key to (a) Classification of Recommendations:
Class I: benefit >>> risk;
Class IIa benefit >> risk;
Class IIb benefit ≥ risk;
Class III: no benefit.
Key to (b) Levels of Evidence:
A: Data derived from multiple randomized controlled trials or meta-analyses; multiple populations evaluated;
B: Data derived from a single randomized controlled trial or non-randomized studies; limited populations evaluated.
C: Only consensus opinion of experts, case studies, or standard of care; very limited populations evaluated.
Society of Vascular Surgery (SVS)
In 2011, the SVS of Vascular Surgery issued updated guidelines for management of extracranial carotid disease, which are summarized in Table 5. (68)
Table 5. Guidelines for Management of Extracranial Carotid Disease
Level of Evidenceb
In most patients with carotid stenosis who are candidates for intervention, CEA is preferred to CAS for reduction of all-cause and periprocedural death.
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 body.
CAS is preferred over CEA in symptomatic patients with >50% stenosis and severe uncorrectable coronary artery disease, congestive heart failure, or chronic obstructive pulmonary disease.
There are insufficient data to recommend CAS as primary therapy for neurologically asymptomatic patients with 70% to 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%.
CAS: carotid artery stenting;
CEA: carotid endarterectomy;
Key to (a) Grade:
Grade I: benefit clearly outweighs risk;
Grade II: benefits and risks are more closely matched and are more
dependent on specific clinical scenarios.
Key to (b) Levels of Evidence:
A: High Quality;
B: Moderate Quality;
C: Low Quality.
European Society of Cardiology (ESC)
In 2011, the ESC issued guidelines on the diagnosis and treatment of peripheral artery diseases, which included recommendations regarding carotid revascularization, summarized in Table 6. (69)
Table 6. Guidelines on the Diagnosis and Treatment of Carotid Artery Diseases
Level of Evidenceb
In symptomatic patients at high surgical risk requiring revascularization, CAS should be considered as an alternative to CEA.
In symptomatic patients requiring carotid revascularization, CAS may be considered as an alternative to CEA in high-volume centers with documented death or stroke rate <6%.
CAS: carotid artery stenting;
CEA: carotid endarterectomy;
ESC: European Society of Cardiology.
Key to (a) Classification of Recommendations:
Class IIa: Should be considered;
Class IIb: May be considered;
Key to (b) Levels of Evidence:
A: Data derived from multiple randomized clinical trials or meta-analyses.
B: Data derived from a single randomized clinical trial or large nonrandomized studies.
C: Consensus of opinion of the experts and/or small studies, retrospective studies, registries.
National Institute for Health and Clinical Excellence (NICE)
NICE issued the following guidance in 2011 on CAS (70):
“Current evidence on the safety of CAS placement for asymptomatic extracranial carotid stenosis shows well documented risks, in particular, the risk of stroke. The evidence on efficacy is inadequate in quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.”
Australasian Carotid Stenting Guidelines Committee
The Royal Australasian College of Physicians, Royal Australasian College of Surgeons, and Royal Australian and New Zealand College of Radiologists issued joint recommendations in 2011 on CAS (71):
“CAS may be considered as a treatment option for patients with symptomatic severe carotid stenosis who are at high-risk of stroke, but are surgically unsuitable for CEA, namely postradiation therapy, block dissection of the neck, in situ tracheostomy, recurrent stenosis following previous CEA, severe cervical spine arthritis, surgically inaccessible carotid stenosis (e.g., obesity, high carotid bifurcation), contralateral recurrent laryngeal nerve injury, and contralateral internal carotid occlusion.”
“The overall results of randomized controlled trials indicate that CAS is not as safe as CEA for treatment of symptomatic carotid stenosis for prevention of ipsilateral stroke.”
“There is currently no evidence to support CAS as a treatment for asymptomatic carotid stenosis.”
Medicare National Coverage
In March 2001, the Center for Medicaid and Medicare Services (CMS) issued national coverage policy that restricted coverage for carotid angioplasty and stenting to patients participating in a clinical trial with category B investigational device exemption (IDE) designation from the FDA. Percutaneous transluminal angioplasty of the vertebral and cerebral arteries remained noncovered.
When the FDA approved the first (Guidant) devices, Medicare coverage under the IDE was no longer available for that manufacturer’s devices and was not applicable to FDA-required postapproval studies. Thus, in October 2004, Medicare broadened its national coverage policy and “determined that the evidence is adequate to conclude that percutaneous transluminal angioplasty (PTA) with carotid stent placement is reasonable and necessary when performed consistent with FDA approval of the carotid stent device and in an FDA required post-approval study.” For unapproved stents and EPDs, the prior policy remained in effect and restricted coverage to patients participating in an FDA-approved category B IDE trial of stent placement in the cervical carotid artery.
While the Medicare decision differed from the conclusions of this policy, Medicare made a public policy decision “that making available new, effective therapies aimed at addressing treatment and prevention of cerebrovascular disease was important to Medicare beneficiaries.” Medicare also noted that it recognized value in supporting postapproval studies as “the collected data may provide an opportunity for practitioners to determine which patients are most appropriate for carotid artery stenting and to reinforce IDE trial data on health outcomes and adverse events.”
CMS provides a continually updated listing of facilities eligible for Medicare reimbursement that meet CMS's minimum facility standards for performing carotid artery stenting for high-risk patients.
In March 2005, CMS determined that CAS with EPD was reasonable and necessary for patients at high-risk for CEA who also have symptomatic carotid artery stenosis 70% or more. CMS limited coverage for these patients to procedures performed using FDA-approved devices. CMS also limited coverage for patients at high-risk for CEA with symptomatic carotid artery stenosis between 50% and 70%, and for patients at high-risk for CEA with asymptomatic stenosis 80% or more, to FDA-approved category B IDE clinical trials for unapproved devices, or to FDA-required postapproval studies for approved devices. CMS defined patients at high-risk for CEA as having significant comorbidities and/or anatomic risk factors (i.e., recurrent stenosis and/or previous radical neck dissection) who would be poor candidates for CEA in the opinion of a surgeon.
In April 2007, a decision memo reaffirmed CMS’s previous decision following a request to expand coverage while clarifying that “CAS is only covered when used with an embolic protection device and is, therefore, not covered if deployment of the distal embolic protection device is not technically possible.” In October 2008, in a sixth reconsideration, and in December 2009, in a seventh reconsideration, CMS reaffirmed its prior coverage decisions.
In January 2012, CMS convened a Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) panel to consider management of carotid atherosclerosis. MEDCAC panel members voted on specific questions using a scale of 1 (low confidence) to 5 (high confidence). For symptomatic patients not considered at high-risk, the mean scores to the question of whether CAS is the favored treatment strategy in this population was 1.85 and for CEA 3.6. For asymptomatic patients not considered high-risk, the evidence was not judged to have reached a level of certainty to provide allow determining a favored treatment.
Summary of Evidence
For individuals who have carotid artery stenosis who receive carotid artery stenting (CAS), the evidence includes randomized controlled trials (RCTs) and systematic reviews of RCTs. Relevant outcomes are overall survival, morbid events, and treatment-related mortality and morbidity. A substantial body of RCT evidence compares outcomes of CAS to carotid endarterectomy (CEA) for symptomatic and asymptomatic patients with carotid stenosis. The evidence does not support 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 no better. Data from RCTs and large database studies have established that the risk of CAS exceeds the threshold set 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
However, based on limited data, clinical input, an indirect chain of evidence, and unmet medical need, CAS may be considered a reasonable treatment option in recently symptomatic patients when CEA cannot be performed due to anatomic reasons. For this population, CAS may be considered medically necessary. It is considered experimental, investigational and/or unproven for all other indications, including carotid dissection. For asymptomatic patients not considered at high-risk, the evidence is insufficient as a reasonable treatment option for this population group. The lack of adequate studies and comparisons in RCT’s does not support carotid angioplasty with or without stenting and is considered experimental, investigational and/or unproven.
Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
In 2015 CPT codes 37215 and 37216 were revised to include open and percutaneous transcatheter placement. The procedure would also include angioplasty, when done, and all associated radiological supervision and interpretation.
The new 2014 CPT Category I code, 37217, indicates the procedure is performed transcervically or by retrograde approach, but is still considered carotid stenting. The intravascular stent placement is accomplished by open ipsilateral cervical carotid exposure.
Disclaimer for coding information on Medical Policies
Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.
The following codes may be applicable to this Medical policy and may not be all inclusive.
37215, 37216, 37217, 37218, 0075T, 0076T
ICD-9 Diagnosis Codes
Refer to the ICD-9-CM manual
ICD-9 Procedure Codes
Refer to the ICD-9-CM manual
ICD-10 Diagnosis Codes
Refer to the ICD-10-CM manual
ICD-10 Procedure Codes
Refer to the ICD-10-CM manual
The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.
The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.
A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.
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|10/15/2018||Reviewed. No changes.|
|10/15/2017||Document updated with literature review. The following indication was added to the experimental, investigational and/or unproven coverage statement, “patients who are not considered high-risk and are asymptomatic.”|
|10/1/2016||Reviewed. No changes.|
|8/15/2015||Document updated with literature review. Coverage unchanged.|
|10/15/2014||Document updated with literature review. Coverage unchanged. CPT/HCPCS code(s) updated.|
|9/15/2012||New medical document. Carotid angioplasty with associated stenting and embolic protection may be considered medically necessary when meeting specific criteria; otherwise carotid angioplasty with or without associated stenting and embolic protection is considered experimental, investigational and unproven. (This topic was previously addressed on MED202.032 Angioplasty and Stenting for Vascular Occlusive Disease.)|
|Title:||Effective Date:||End Date:|
|Extracranial Carotid Angioplasty or Stenting||10-15-2017||10-14-2018|
|Extracranial Carotid Angioplasty or Stenting||10-01-2016||10-14-2017|
|Extracranial Carotid Angioplasty or Stenting||08-15-2015||09-30-2016|
|Extracranial Carotid Angioplasty or Stenting||10-15-2014||08-14-2015|
|Extracranial Carotid Angioplasty or Stenting||09-15-2012||10-14-2014|