Percutaneous Transluminal Angioplasty (PTA) of the Carotid Artery Concurrent with Stenting

The Centers for Medicare & Medicaid Services (CMS) proposes that coverage of percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting is reasonable and necessary with the placement of a Food and Drug Administration (FDA) approved carotid stent with an FDA-approved or cleared embolic protection device, for Medicare beneficiaries under the following conditions:

1. Patients with symptomatic carotid artery stenosis ≥50%; and
2. Patients with asymptomatic carotid artery stenosis ≥70%.

For both A and B above:
1. Independent neurological assessment before and after carotid artery stenting (CAS) must be performed to assess procedural risks.
2. Evaluation of the extent and severity of carotid artery stenosis must use one of the following non-invasive modalities for first-line imaging: duplex ultrasound, computed tomography angiography, or magnetic resonance angiography.
   1. If duplex ultrasound is used as first-line imaging, computed tomography angiography or magnetic resonance angiography must also be performed to provide additional information about the aortic arch, and extra- and intra-cranial circulation, for better patient selection.
   2.  If either computed tomography angiography or magnetic resonance angiography is used as first-line imaging, no second-line imaging is required.
   3. Intra-arterial digital subtraction (catheter) angiography must not be used for first-line imaging, and may be used only when there is significant discrepancy between non-invasive imaging results.

Prior to furnishing CAS, the practitioner must engage in a formal shared decision-making interaction with the beneficiary. The shared decision-making interaction must involve the use of a validated shared decision-making tool and include:

• Discussion of all treatment options for carotid stenosis to ensure the beneficiary is familiar with and aware of all treatment options including, but not limited to, procedures that fall within the parameters of this NCD.
• Explanation of risks and benefits for each option specific to the beneficiary’s clinical condition.
• Integration of clinical guidelines (e.g., patient life-expectancy).
• Discussion and incorporation of beneficiary’s personal preferences and priorities in choosing a treatment plan.

In addition to the national coverage described above, Medicare Administrative Contractors (MACs) may make reasonable and necessary determinations under section 1862(a)(1)(A) for any other beneficiary seeking coverage for PTA of the carotid artery concurrent with stenting.

See Appendix B for the proposed manual language.

In summary, our proposals, which affect NCD 20.7 sections B4 and D, will revise Medicare coverage for PTA of the carotid arteries concurrent with stenting by:

1. Expanding coverage to individuals previously only eligible for coverage in clinical trials;
2. Expanding coverage to standard surgical risk individuals by removing the limitation of coverage to only high surgical risk individuals;
3. Removing facility standards and approval requirements;
4. Adding formal shared decision-making with the individual prior to furnishing CAS; and
5. Allowing MAC discretion for all other coverage of PTA of the carotid artery concurrent with stenting not otherwise addressed in NCD 20.7.

CMS is seeking comments on our proposed decision.  In particular, we are requesting comments on whether the shared decision-making interaction should require the use of a validated shared decision-making tool and/or if there are other options to achieve the goal of truly informed decision-making. We will respond to public comments in a final decision memorandum, as required by §1862(l)(3) of the Social Security Act (the Act).

TO: 		 Administrative File:  CAG-00085R8 

FROM:		Coverage and Analysis Group (CAG)

SUBJECT: 	Proposed National Coverage Determination for Percutaneous Transluminal Angioplasty (PTA) of the Carotid Artery Concurrent with Stenting

DATE: 		July 11, 2023

I. Proposed Decision

The Centers for Medicare & Medicaid Services (CMS) proposes that coverage of percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting is reasonable and necessary with the placement of a Food and Drug Administration (FDA) approved carotid stent with an FDA-approved or cleared embolic protection device, for Medicare beneficiaries under the following conditions:

1. Patients with symptomatic carotid artery stenosis ≥50%; and
2. Patients with asymptomatic carotid artery stenosis ≥70%.

For both A and B above:
1. Independent neurological assessment before and after carotid artery stenting (CAS) must be performed to assess procedural risks.
2. Evaluation of the extent and severity of carotid artery stenosis must use one of the following non-invasive modalities for first-line imaging: duplex ultrasound, computed tomography angiography, or magnetic resonance angiography.
   1. If duplex ultrasound is used as first-line imaging, computed tomography angiography or magnetic resonance angiography must also be performed to provide additional information about the aortic arch, and extra- and intra-cranial circulation, for better patient selection.
   2.  If either computed tomography angiography or magnetic resonance angiography is used as first-line imaging, no second-line imaging is required.
   3. Intra-arterial digital subtraction (catheter) angiography must not be used for first-line imaging, and may be used only when there is significant discrepancy between non-invasive imaging results.

Prior to furnishing CAS, the practitioner must engage in a formal shared decision-making interaction with the beneficiary. The shared decision-making interaction must involve the use of a validated shared decision-making tool and include:

• Discussion of all treatment options for carotid stenosis to ensure the beneficiary is familiar with and aware of all treatment options including, but not limited to, procedures that fall within the parameters of this NCD.
• Explanation of risks and benefits for each option specific to the beneficiary’s clinical condition.
• Integration of clinical guidelines (e.g., patient life-expectancy).
• Discussion and incorporation of beneficiary’s personal preferences and priorities in choosing a treatment plan.

In addition to the national coverage described above, Medicare Administrative Contractors (MACs) may make reasonable and necessary determinations under section 1862(a)(1)(A) for any other beneficiary seeking coverage for PTA of the carotid artery concurrent with stenting.

See Appendix B for the proposed manual language.

In summary, our proposals, which affect NCD 20.7 sections B4 and D, will revise Medicare coverage for PTA of the carotid arteries concurrent with stenting by:

1. Expanding coverage to individuals previously only eligible for coverage in clinical trials;
2. Expanding coverage to standard surgical risk individuals by removing the limitation of coverage to only high surgical risk individuals;
3. Removing facility standards and approval requirements;
4. Adding formal shared decision-making with the individual prior to furnishing CAS; and
5. Allowing MAC discretion for all other coverage of PTA of the carotid artery concurrent with stenting not otherwise addressed in NCD 20.7.

CMS is seeking comments on our proposed decision.  In particular, we are requesting comments on whether the shared decision-making interaction should require the use of a validated shared decision-making tool and/or if there are other options to achieve the goal of truly informed decision-making. We will respond to public comments in a final decision memorandum, as required by §1862(l)(3) of the Social Security Act (the Act).

II. Background

Throughout this document we use numerous acronyms, some of which are not defined as they are presented in direct quotations.  Please find below a list of these acronyms and corresponding full terminology:

ACAS – Asymptomatic Carotid Atherosclerosis Stenosis
ACST-2 – Asymptomatic Carotid Surgery Trial-2
ACT-1 – Asymptomatic Carotid Trial
BMT – Best Medical Therapy
CAS – Carotid Artery Stenting
CEA – Carotid Endarterectomy
CMS – Centers for Medicare & Medicaid Services
CREST – Carotid Revascularization Endarterectomy versus Stenting Trial
CREST-2 – Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial
CTA – Computed Tomography Angiography
ECST-2 – Second European Carotid Surgery Trial
EPD – Embolic Protection Device
FDA – Food and Drug Administration
IDE – Investigational Device Exemption
MAC – Medicare Administrative Contractor
MI – Myocardial Infarction
MRA – Magnetic Resonance Angiography
MSCA – Multispecialty Carotid Alliance
NASCET – North American Symptomatic Carotid Endarterectomy Trial
NCA – National Coverage Analysis
NCD – National Coverage Determination
OMT – Optimal Medical Therapy
PTA – Percutaneous Transluminal Angioplasty
ROADSTER – Reverse Flow Used During Carotid Artery Stenting Procedure
SAPPHIRE – Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy
SDM – Shared Decision-Making
SPACE-2 – Stent Protected Angioplasty versus Carotid Endarterectomy-2
TCAR – Transcarotid Artery Revascularization

The terms “procedural” and “periprocedural” are used interchangeably in the literature, and in this NCD, as are the terms “best medical therapy or BMT” and “optimal medical therapy or OMT.”

Strokes occur when blood flow to the brain is blocked (ischemic stroke) or sudden bleeding in the brain occurs (hemorrhagic stroke) (NINDS 2023).  In the United States, more than 795,000 people experience a stroke annually and ischemic strokes comprise about 87% of all strokes (CDC 2023).  The carotid arteries supply oxygenated blood to the brain and are susceptible to atherosclerosis which can result in carotid artery stenosis and plaque embolization (Sethi 2023).  Carotid atherosclerosis develops when plaque, formed by cholesterol, fat, blood cells and other substances in the blood, builds up inside the carotid arteries, to narrow the arteries and reduce blood flow (NHLBI 2023, NINDS 2023).  Carotid atherosclerotic disease accounts for about 10-20% of ischemic strokes, or about 150,000 strokes each year in the United States (Finn 2017).

Treatment strategies for atherosclerotic carotid stenosis include aggressive medical therapy, carotid endarterectomy (CEA) and carotid artery stenting (CAS).  Aggressive medical therapy may involve use of anti-platelet agents, statins, antihypertensives, anti-ischemic perioperative beta blockers, risk factor modification (including smoking cessation and diabetic control) plus lifestyle modification (e.g., exercise).

CEA is a surgical procedure used to prevent stroke in which a surgeon removes fatty deposits or ulcerated and stenotic plaques from the carotid arteries, the two main arteries in the neck supplying blood to the brain.

CAS is performed with a catheter, usually inserted through the femoral artery, and threaded up to the carotid artery beyond the area of narrowing.  A distal embolic protection device or filter is usually placed first to catch emboli or debris that may dislodge during the procedure.  A self-expandable or balloon-expandable, metal mesh stent is then placed to widen the stenosis and the protection device is removed.  CAS procedures using the femoral access point are often referred to as transfemoral CAS (TF-CAS) following the advent of the newest CAS procedure, transcarotid artery revascularization (TCAR).  TCAR accesses the carotid arteries percutaneously through an incision above the collarbone and uses a proximal embolic protection device involving blood flow reversal instead of distal embolic protection.

III. History of Medicare Coverage

Medicare first covered PTA of the carotid artery concurrent with stent placement in accordance with the FDA approved protocols governing Category B IDE clinical trials and later in FDA required post approval studies (Medicare NCD Manual 20.7B2, B3).  Our proposals do not involve revisions to subsections B2 and B3.

Effective March 17, 2005, Medicare expanded coverage for PTA and stenting of the carotid artery when performed on patients at high risk for CEA who also have symptomatic carotid artery stenosis ≥ 70% only when performed in a CMS approved facility for CAS with FDA-approved carotid artery stenting systems and embolic protection devices.  Symptoms of carotid artery stenosis include carotid transient ischemic attack (TIA) (distal focal neurological dysfunction persisting less than 24 hours), non-disabling stroke (Modified Rankin Scale score < 3 with symptoms for 24 hours or more), and transient monocular blindness (amaurosis fugax) (Medicare NCD Manual 20.7B4).

Effective April 30, 2007, Medicare maintained the existing coverage policy and included detailed facility recertification instructions in the NCD.

Effective October 14, 2008, Medicare maintained the existing coverage policy, making no deletions, revisions or additions.

Effective December 9, 2009, Medicare revised the NCD language to specify that FDA approved or cleared embolic protection devices may be used during CAS procedures.  No changes were made to other coverage requirements or criteria.

A.  Current Request

CMS received and accepted a complete, formal request to reconsider NCD 20.7 from the Multispecialty Carotid Alliance (MSCA).  The request letter is available at https://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id311.pdf.  The scope of this reconsideration is limited to PTA concurrent with CAS including transcarotid artery revascularization (TCAR) procedures.

B. Benefit Category

For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Social Security Act [§1812 (Scope of Part A); §1832 (Scope of Part B); §1861(s) (Definition of Medical and Other Health Services)].
PTA of the carotid artery concurrent with stenting qualifies as:

• Inpatient hospital services.
• Physicians’ services.

Note: This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service.

IV. Timeline of Recent Activities 

V.  Food and Drug Administration (FDA) Status

On August 30, 2004, the FDA approved the first carotid stent for marketing in the United States. The ACCULINK™ Carotid Stent System and the RX ACCULINK™ Carotid Stent System, used in conjunction with Guidant carotid embolic protection systems, was approved “for the treatment of patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the criteria outlined below.

(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P040012).

Since this first approval, the devices in Table 1 below have been approved for:

• Standard (i.e., non-high) surgical risk patients; and
• Stenting via direct carotid artery access (TCAR) vs. traditional femoral artery access (CAS).

Table 1 below provides a timeline of carotid stent device approvals to date.

Table 1 – FDA approved carotid stent devices

VI. General Methodological Principles

When making national coverage determinations (NCDs) under section 1862(a)(1)(A) of the Social Security Act, CMS generally evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.  The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for beneficiaries.  An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary.

A detailed account of the methodological principles of study design that the Agency utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix A.

Public comments sometimes cite published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination.  Public comments that contain personal health information that cannot be redacted will not be made available to the public.  CMS responds in detail to the public comments on a proposed national coverage determination when issuing the final national coverage determination.

VII. Evidence

A. Introduction

B. Discussion of Evidence

1. Evidence Questions

Q1.  Does carotid artery stenting with embolic protection improve health outcomes similarly to carotid endarterectomy in symptomatic patients with carotid artery stenosis?

Q2. Does carotid artery stenting with embolic protection improve health outcomes similarly to carotid endarterectomy in asymptomatic patients with carotid artery stenosis?

Q3.  Do specific patient characteristics impact which procedure, CAS or CEA, results in better health outcomes for individual patients?

Q4.  Are NCD criteria for physicians, care teams, and facilities performing CAS necessary or helpful to ensure that beneficial health outcomes seen in trials are achieved in broad community practice?

2. External Technology Assessments

CMS did not request an external technology assessment (TA) on this issue.

3. Internal Technology Assessment

We searched the databases PubMed and Embase for English language articles in peer-reviewed journals published since the last NCD, from 2009-2023, using the search terms ‘carotid artery stenting’, ‘carotid endarterectomy’, ‘transcarotid artery revascularization’ and “healthcare disparities” in various combinations.  To ensure that we captured all the relevant articles, the search was conducted independently by the contractor International Consulting Associates (ICA), and the CMS Coverage and Analysis Group (CAG).  We incorporated all the distinct, relevant references into a single reference database.  We included other, relevant articles and documents cited by those in the reference database, or cited by the requester and public commenters, as well as expert opinion or commentary from online sources.  We also searched for the most recent guidelines by medical societies, based in the U.S. and abroad, as well as relevant government reports (e.g., by the FDA or CDC).  The final result was the identification of over 70 peer-reviewed documents relevant to the NCD analysis.

4. Medicare Evidence Development & Coverage Advisory Committee (MEDCAC)

A MEDCAC meeting was not convened on this issue.

5. Evidence Table

Link to evidence table.

VIII. Public Comment

Public comments sometimes cite the published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination.

CMS uses the initial public comments to inform its proposed decision. CMS responds in detail to the public comments on a proposed decision when issuing the final decision memorandum. All comments that were submitted without personal health information may be viewed in their entirety by using the following link: https://www.cms.gov/medicare-coverage-database/view/ncacal-public-comments.aspx?ncaid=311.

Initial Comment Period: 1/12/2023-2/11/2023

During the 30-day public comment period following the release of the tracking sheet, CMS received 193 timely comments.  All comments were published on the CMS website and considered for this proposed decision.  The majority of comments, 146 comments, supported the expansion of coverage criteria in one or more areas. Of these 146 comments, 75 comments specifically supported removal of the requirement that patients are at high risk for CEA, 21 comments specifically supported removal of the operator and facility standards and approval requirements, and 3 comments supported expansion of coverage only for TCAR and not transfemoral CAS.  Twenty-three comments did not support expansion.  Of these 23 comments, 2 comments did not support removal of the requirement that patients are at high risk for CEA, and 4 comments did not support the removal of the operator and facility standards and approval requirements.  Three comments supported expansion of coverage criteria in some areas and non-expansion in others.  Twenty-one comments did not state a clear position regarding coverage criteria. Of these 21 comments, 10 comments were generally positive toward transfemoral CAS and 3 comments were generally positive toward TCAR.  One comment supported independent facility accreditation for all carotid stenting procedures and operator guidelines provided by professional societies.

One hundred fifty-six comments were submitted by healthcare professionals, with the majority (at least 145 comments) provided by physicians.  Seven comments were provided by medical device companies.  Seventeen commenters did not specify their titles and/or organizations. Thirteen comments were provided by national associations, professional societies, commissions, foundations, including the Intersocietal Accreditation Commission (IAC), the Multispecialty Carotid Alliance (MSCA), the Society for Cardiovascular Angiography and Interventions (SCAI), the Society of Interventional Radiology (SIR), the Society of NeuroInterventional Surgery (SNIS), the Society of Vascular and Interventional Neurology (SVIN), the Society for Vascular Medicine (SVM), the Society for Vascular Surgery (SVS), the Society for Vascular Surgery (SVS) Patient Safety Organization (PSO) Vascular Quality Initiative (VQI), the Vascular InterVentional Advances (VIVA) Foundation, a joint comment from the American College of Cardiology (ACC) and the American Heart Association (AHA), and a joint comment from the American Association of Neurological Surgeons (AANS), the Congress of Neurological Surgeons (CNS), and the AANS/CNS Joint Section on Cerebrovascular Neurosurgery.

Numerous commenters provided references for our deliberation of this NCA.  We very much appreciate this information.  All such references were assessed for inclusion in our evidence review.

IX. CMS Analysis

Introduction

National coverage determinations (NCDs) are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally by Medicare (§1869(f)(1)(B) of the Act).  In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B, and must not be otherwise excluded from coverage.  Moreover, with limited exceptions, the expenses incurred for items or services must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§1862(a)(1)(A) of the Act).

When making NCDs, we evaluate the evidence related to our analytic questions based on the quality, strength and totality of evidence presented in the reviewed literature.  As part of this evaluation, it is important to consider whether the evidence is relevant to the Medicare beneficiary population.  In determining the generalizability of the results of the body of evidence to the Medicare population, we consider, at minimum, the age, race and sex of the study participants.

Summary

We are reconsidering certain aspects of section 20.7 of the Medicare National Coverage Determinations manual, Percutaneous Transluminal Angioplasty (PTA) of the Carotid Artery Concurrent with Stenting.  Specifically, we are reconsidering NCD 20.7, B4, which covers stenting with embolic protection devices (EPDs) for symptomatic patients with carotid artery stenosis ≥70% who are considered “high surgical risk” for carotid endarterectomy (CEA).  Section B4 of the NCD also covers other, including asymptomatic, patients in the context of studies (CMS 2009).  We propose at section B4 of the NCD to cover PTA of the carotid artery concurrent with stenting with EPDs for symptomatic patients with carotid artery stenosis ≥50% or asymptomatic patients with carotid artery stenosis ≥70%.  We are proposing to eliminate facility requirements that are no longer necessary.

We also propose to add language at NCD 20.7, D (“Other”) to enable MACs to make reasonable and necessary determinations under section 1862(a)(1)(A) for other Medicare beneficiaries who do not meet the coverage criteria in section B but are seeking Medicare coverage for PTA of the carotid artery concurrent with stenting.

Our current NCD is based on earlier trials comparing carotid artery stenting (CAS) to CEA.  These in turn were based on the superiority of CEA over medical therapy in foundational trials launched three decades ago, in patients who were symptomatic (NASCET, ECST trials) or asymptomatic (ACAS trial).  Even for asymptomatic patients, CEA “halved the subsequent rate of disabling or fatal stroke” compared to medical therapy alone (Halliday 2010), although the absolute difference (6%) was small (Walker 1995, Halliday 2004).

Since the last CMS reconsideration in 2009, papers on five major RCTs comparing CAS to CEA have been published along with large, prospective registry-based studies, and meta-analyses of pooled trial data.  We propose that this new evidence, especially now for asymptomatic patients, suffices to demonstrate that CAS and CEA are similarly effective with respect to the composite primary outcomes of recent trials (which have included various combinations of disabling stroke, death, any stroke, and myocardial infarction) in patients with either standard or high surgical risk, and who are symptomatic with carotid artery stenosis ≥50% or asymptomatic with stenosis ≥70%.

“Symptomatic” patients are those with recent transient ischemic attack, stroke, or other relevant neurologic signs or symptoms as defined in contemporary trials.  “Asymptomatic” patients are those without a recent neurological event but with carotid atherosclerosis on imaging.  Consistent with every recent societal guideline, all patients should have a reasonable life expectancy (>3 or >5 years depending on the guideline) in order to experience benefit from the procedure (i.e., to overcome procedure-related adverse events, which medical therapy does not entail).  We are proposing to require a formal patient-physician shared decision-making (SDM) visit because of the importance of individual patient anatomy, pathophysiology, and preferences, and as CAS and CEA entail different procedural (30-day) risks (minor stokes generally being more common with CAS; myocardial infarction (MI) and cranial nerve palsies, with CEA).

While not a requirement under this NCD, individuals undergoing a carotid revascularization procedure should be provided with optimal medical therapy (OMT) for atherosclerotic disease, including lifestyle/behavioral modification counseling, tailored to the individual patient.  The aim is to reduce all-cause and cardiac mortality in addition to carotid-related stroke and mortality, and (perhaps) to protect against long-term cognitive decline (Paraskevas 2022, Lancet 2021, Balestrini 2013).  Such medical therapy is often reflected in the latest societal guidelines, if published recently (e.g., the 2023 European Society of Vascular Surgeons (ESVS) clinical guideline is now available (Naylor 2022); it is also the only guideline to date that incorporates the most recent CAS vs CEA trial for asymptomatic patients, ACST-2).

We recognize that the medical therapy that served as the control group treatment in the early, foundational trials has also vastly improved.  Thus, contemporary trials comparing CEA to CAS reviewed in this NCD analysis, with their wide use of modern antithrombotic, antihypertensive, and lipid-lowering drugs, and lifestyle risk-modification, as background medical therapy for both groups, can fairly compare the two procedures.  However, these trials do not answer the question of whether any procedure produces better health outcomes than contemporary OMT alone for these patients.  This highlights the importance of completing and publishing ongoing trials which compare each procedure to OMT alone (e.g., CREST-2 and ECST-2).

CMS is not proposing specific physician, care team, or facility requirements in this NCD.  Standards for these are important, but adequately exist in societal guidelines, are backed by evidence from contemporary randomized trials, continue to evolve, and provider, patient, and outcomes data housed at local facilities can be audited or reviewed by appropriate entities.  That said, we note that a standardized, nationwide registry – for all carotid artery procedures – would be helpful to monitor procedural safety, further evolve patient risk stratification, and to facilitate auditing and quality improvement, including comparison of local outcomes to national and other benchmarks.  It would be helpful wherever possible that large-scale, data-collection enterprises (registries) collaborate, include all patients, and build off existing infrastructure rather than create anew.  Similar collection of outcomes data for patients on OMT alone would be informative. Results of ongoing trials, such as CREST-2 and ECST-2, may better inform registry content.

Our analysis and proposed decision do not:

• Distinguish, for purposes of coverage criteria, among different:
  • approaches for deploying FDA-approved stent systems (e.g., transfemoral, transradial, or transcarotid);
  • types of FDA-approved stents (e.g., open cell, closed cell, dual layer); and
  • types of FDA-approved devices and methods for embolic protection (e.g., proximal or distal protection, or use of flow reversal).
• Address the timing of carotid artery procedures after neurological events, or the appropriate sequence for multiple procedures (e.g., for patients in need of both carotid and coronary revascularization).
• Specify performance criteria for physicians, care teams, or facilities.
• Assess carotid procedures compared to OMT alone.  While observational studies support the case for OMT, these merely provide the clinical equipoise for the definitive, ongoing randomized trials.  Assessment awaits trial results.

Answers to the Four Reconsideration Questions

Our answers to the four key questions for this NCD reconsideration are based on: a review of the trial evidence and relevant reports (discussed in greater depth in the Evidence Review below) since the 2009 reconsideration; internal review across CMS coverage policies to promote consistency; and feedback during the public comment period.  All four questions are with respect to Medicare beneficiaries.

Q1.  Does carotid artery stenting with embolic protection improve health outcomes similarly to carotid endarterectomy in symptomatic patients with carotid artery stenosis?

Our answer is yes, and CAS does so for symptomatic patients with standard as well as high surgical risk (as these terms are described in recent trials).  Based primarily on the CREST trial (half of which were symptomatic patients) and ICSS trial (symptomatic patients only), the evidence is stronger for patients with carotid artery stenosis ≥70%; however, we believe it is sufficient for patients with ≥50% stenosis as well.  The reason for the relatively weaker evidence for the ≥50% stenosis mark is that while inclusion criteria for both trials was carotid stenosis ≥50%, in fact the vast majority of patients had stenosis ≥70% (86% for CREST and 89% for ICSS).  This may reflect reluctance of physicians to refer patients with moderate stenosis at that time.  However, there is evidence supporting CAS for carotid stenosis of 50-69%, and we believe it is less helpful if CEA was the only procedural option for these patients, regardless of patient anatomy and other characteristics (see Q3 below).

How carotid artery stenosis is measured matters.  In contemporary practice and trials alike, carotid stenosis is appropriately measured by noninvasive means, primarily duplex (Doppler vascular and B mode) ultrasound, with confirmation by CT or MR angiography (CTA or MRA).  This is because of improvements in non-invasive imaging modalities, and because interventional (catheter) angiography is itself associated with increased risk of stroke.  Both CTA and MRA also provide additional information about anatomy (e.g., aortic tortuosity), and characteristics and locations of atherosclerotic plaques, which are crucial for selecting the right procedure for the individual patient.  The importance of patient selection is a primary reason for patient-doctor shared decision-making (SDM), discussed in Q3 below.

Q2.  Does carotid artery stenting with embolic protection improve health outcomes similarly to carotid endarterectomy in asymptomatic patients with carotid artery stenosis?

Our answer here is yes as well, and again for patients with standard as well as high surgical risk.  The publication of ACST-2, the largest and most recent of any CAS vs CEA trial, has reversed the historical trend in which there has always been better evidence for carotid procedures in symptomatic than in asymptomatic patients.  The ACST-2 trial supports coverage of asymptomatic patients with standard risk and carotid artery stenosis ≥70% (again, by duplex ultrasound with assistance by CT and MR angiography).  Similar outcomes from a large, national registry support the conclusion that trial findings are generalizable to broad community practice.

For both symptomatic and asymptomatic patients with carotid artery stenosis, while guidelines and meta-analyses of trial data are supportive, the most convincing evidence comes from the most recent individual trials themselves.  However, the evidence to date does not compare either procedure to OMT alone, which has also vastly improved over the last decade; that comparison awaits publication of trials like CREST-2 and ECST-2.  We look forward to reading those trial reports.

Q3.  Do specific patient characteristics impact which procedure, CAS or CEA, results in better health outcomes for individual patients?

Yes.  There is a growing body of evidence on which patients might be better suited for the respective procedures. Contemporary risk stratification includes not just patient age and comorbidities (e.g., presence and severity of heart disease, lung disease, diabetes, hypertension, obesity, history of stroke or MI), which are typically assessed before any surgery, but also, for carotid procedures, relevant arterial anatomy, and characteristics, locations and extent of atherosclerotic plaques to include above and below the carotid bulb. 

For example, a recent review states, “there are a variety of clinical and imaging features associated with the risk of future stroke in asymptomatic carotid stenosis. They include: (1) stenosis progression; (2) plaque characteristics including morphology, size, and vulnerability; (3) accompanied stroke-related conditions; and (4) microembolization” (Baek 2023).  However, the evidence on patient risk stratification is still growing and has not matured to the extent that would allow us to codify stable, evidence-based criteria into NCD coverage criteria at this time.

Individual patient characteristics thus matter, but so do patient concerns and preferences, especially as there are three management strategies (CAS, CEA, OMT alone), and the two procedures entail different procedural (30-day) risks (minor stokes generally being more common with CAS; MI and cranial nerve palsies, with CEA).  As a clinical example, a patient with no aortic tortuosity, good femoral access, no extensive carotid calcifications, no hypertension or significant white matter disease on brain MRI, but (stable) coronary artery disease, and whose father died in his 50s from an MI, might reasonably select CAS over CEA.  A different patient with a different clinical picture and set of concerns may reasonably select CEA. Many patients will (and probably should) select OMT alone.

We thus are proposing to require formal patient-doctor SDM to ensure that the beneficiary receives up to date information and personalized advice.  Ideally, that advice would come directly from the competing experts: a surgeon, an interventionalist who is not a surgeon, both of whom perform their procedures in accordance with contemporary standards of care (more on this in Q4 below), and an independent physician with expertise in medical management of carotid artery disease, who does not perform procedures.  As part of the SDM encounter, we propose requiring use of a validated, standardized SDM tool to assist in fulfilling this coverage requirement.

Q4.  Are NCD criteria for physicians, care teams, and facilities performing CAS necessary or helpful to ensure that beneficial health outcomes seen in trials are achieved in broad community practice?

We are proposing to discontinue the requirement that facilities meet specific standards and be approved by CMS to perform CAS procedures.  Moreover, CMS is not proposing specific physician, care team, or facility requirements in this NCD.  Analysis of data from large registries support the conclusion that benefits and harms of CAS compared to CEA seen in trials are generalizable to broad community practice.  This is not surprising, as twenty years have passed since the first investigational device exemption (IDE) study was conducted for CAS.  The standard of care for diagnosis and treatment of carotid artery disease, and training to enter this field, has furthermore matured since our 2009 NCD reconsideration.  Currently, provider and individual patient data is maintained at these local facilities, and could be used for continuous quality improvement.  Team approaches to care and acceptable patient outcomes are backed by contemporary trials and guidelines alike.  Thus, appropriate physician and facility experience and outcomes are adequately reflected in current standards of care, and institutional processes (public and private) exist to monitor practice and enforce standards.

Also, the standards themselves are constantly improving.  For example, the current rate for procedural (30-day) disabling stroke or death in asymptomatic patients is now near 1%, and for any stroke or death, below 4% (for either procedure, in trials and registries alike).  The ESVS recommends that providers have a <3% rate for any stroke or death for asymptomatic patients (and <6% for symptomatic ones) – but have hinted that this may change (Naylor 2022).  The SVS guidelines have yet to be updated after ACST-2.  We would not want to codify in an NCD a numeric threshold that may be constantly moving.

Specifically, we are proposing to discontinue the CAS facility approval and recertification requirements to determine that a facility is competent in performing the evaluation, procedure and follow-up necessary to ensure optimal patient outcomes. These standards include specific physician training standards, facility support requirements and data collection and submission requirements.  Please see Appendix C for the complete list of requirements under the facility approval and recertification requirement that will be discontinued.

Evidence Review

The five major, relevant new reports from trials comparing CAS to CEA since the last NCD reconsideration are for: ICSS, CREST, ACT-1, SPACE-2, ACST-2 (see Evidence Table 1 in this proposed decision memorandum).  These five RCTs are all in patients with standard (also called average) surgical risk.  One trial has symptomatic patients (ICSS); one has both symptomatic and asymptomatic patients (CREST), and three have asymptomatic patients (ACT-1, SPACE-2, ACST-2).  As reflected in the 2009 NCD, the evidence for procedural treatment has previously been stronger for symptomatic than for asymptomatic carotid artery disease (CMS 2009).  The ICSS and CREST trials brought additional evidence for CAS treatment of symptomatic patients, including those at average surgical risk (not just those at high risk for adverse events with CEA).  And with the publication of ACST-2 in 2021, the evidence gap for asymptomatic patients with average surgical risk has largely been filled, with this one trial alone doubling the number of total asymptomatic trial patients (Halliday 2021).

Additional key evidence includes studies from large registries, both in the U.S., and in Germany (where by law key data from all carotid procedures must be submitted to one national registry (Klein 2023)). While both early and late outcomes of RCTs remain the gold-standard for unbiased comparison of interventions in terms of safety, efficacy, and clinical utility, the analysis of large, observational registry data may better assess the generalizability of trial data to broad (“real-world”) community practice, which involves greater diversity of patients, clinicians, and treatment centers.

Finally, while meta-analyses of pooled trial data have generally supported the findings of the individual trials, the strongest evidence comes from the most recent trials themselves, using contemporary devices and standards of care, which includes physician credentialing and optimal medical therapy.  We discuss these key trials in greater depth below.

ICSS, CREST and ACT-1 trials (earlier trials, for symptomatic and asymptomatic patients)

Of the trial reports published after the 2009 NCD, these constitute the “early” ones, and have a mix of symptomatic and asymptomatic patients.  ICSS is symptomatic only, ACT-2 is asymptomatic only, and CREST is both.  These “early” trials have in common use of background OMT for both CAS and CEA that is not the contemporary OMT seen, for instance, in the ACST-2 trial (discussed later), or ongoing trials in which OMT is a separate treatment arm directly compared to each procedure.  Late outcomes of the ICSS trial were published in Lancet in 2015, and early and late outcomes of CREST and ACT-1 were published in the same New England Journal of Medicine issue in 2016 (Rosenfield 2016, Brott 2016).

ICSS

ICSS randomized 1,710 symptomatic patients with standard surgical risk and “atherosclerotic carotid stenosis causing at least 50% reduction in carotid artery lumen diameter” to CAS or CEA, with the primary outcome of “fatal or disabling stroke in any territory to end of follow up.”  The final, 10-year report published in 2015 is our focus (Bonati 2015).

Standard surgical risk was described as those patients “deemed equally suited for both treatments” (Bonati 2015), and where the investigators were “uncertain which of the two treatments was the best option for the patient” (ICSS 2010).  This would become the usual wording in later trials for patients not at “high surgical risk” for CEA.  Note that ICSS does not actually use the terms “standard” or “average” regarding patient risk, but the description is consistent with this, and subsequent editorials and reviews use those terms in referring to ICSS (White 2022).  Thus, “patients unsuitable for stenting because of tortuous anatomy proximal or distal to the stenosis, visible thrombus, proximal common carotid artery stenosis, or internal carotid artery pseudo-occlusion were excluded, as were patients unsuitable for endarterectomy because of the distal site of the stenosis, a rigid neck, or risk factors for surgical complications” (with “risk factors” including patient comorbidities; ICSS 2010).  This was a precursor to contemporary risk stratification, itself still evolving.

Stenosis “of at least 50% reduction in carotid artery lumen diameter” refers to the use of interventional (catheter) angiography to measure lumen diameter (a non-interventional equivalent was acceptable but not typical), using NASCET criteria (Ederle 2010, Bonati 2015).  ICSS ended up with roughly 89% of patients having stenosis ≥70%, with the remainder at 50-69% stenosis (Ederle 2010).

“Symptomatic” carotid stenosis was defined as any one or more of the following symptoms or events “attributable to the randomized artery” in the past 12 months: amaurosis fugax, transient ischemic attack (TIA), ischemic hemispheric stroke, or retinal infarction; patients with major prior strokes were excluded (Ederle 2010).  This is consistent with how trials (both early and contemporary) in this 2010-present era would define symptomatic versus asymptomatic patients.  Physicians in turn had to meet certain experience/volume criteria (Ederle 2010).

The ICSS trial found no significant difference between CAS and CEA at 10 years for the primary outcome of fatal or disabling stroke, or for either ipsilateral (same-sided) stroke, or severe restenosis of the treated carotid artery.  CAS had more non-disabling stroke at 30 days and 5 and 10 years, while CEA had more cranial nerve palsies (but not more MIs, as was seen in prior trials) (Bonati 2015).

CREST

CREST evaluated CAS (with embolic protection) vs CEA in 2,502 patients with standard surgical risk who were either symptomatic (and with ≥50% stenosis of the arterial diameter on angiography, by NASCET criteria) or asymptomatic (with stenosis of ≥60% on angiography).  Overall, 86% of patients had carotid stenosis ≥70%.  Associated criteria for stenosis by duplex ultrasound, CTA and MRA were included.  “Symptomatic” patients were defined as having had a transient ischemic attack, amaurosis fugax, or minor nondisabling stroke involving the ipsilateral carotid artery within 6 months before randomization.  “Asymptomatic” patients were those without a recent neurological event but with evidence of carotid atherosclerosis.  Patients with a major stroke at any previous time were excluded from the trial.  Surgeons and interventionalists had to meet experience and outcome criteria, and stenting used embolic protection devices whenever feasible (Brott 2010, 2016; Hopkins 2010).

In the 1-year and 4-year follow-up reports, the trial found no significant difference between CAS and CEA for the primary composite outcome of any stroke, MI, or death from any cause (all-cause mortality) during the periprocedural period (first 30 days post procedure), or for the long-term outcome of any subsequent ipsilateral stroke during 4 years of follow-up (Brott 2010).  At 30-days, CAS had relatively more strokes, while CEA had more MIs and cranial nerve palsies (Figure 1, Supplementary Appendix, Brott 2010).  The early report was evaluated in the 2009 NCD (CMS 2009).

The long-term outcome (ipsilateral stroke after the periprocedural period among patients who had had no periprocedural event) was chosen with the rationale that the purpose of the procedure is to prevent future stroke in the cerebral artery territory fed by the treated carotid artery (Brott 2016).

Ten years was chosen for follow up because the mean age of patients at the start of the trial was 69 years, and “at that age the average life expectancy is 15 years for men and 17 years for women” (Brott 2016).  At 10 years, the authors found that for 2,502 asymptomatic (47.2%) and symptomatic (52.8%) patients, there was no significant difference for the early primary composite outcome between CAS (11.8%) and CEA (9.9%), or for the late primary outcome (any ipsilateral stroke) between CAS (6.9%, or 0.7% per year) and CEA (5.6%, or ~0.6% per year).  The combined risk of periprocedural stroke or death and subsequent ipsilateral stroke was 37% higher for CAS than CEA; this was driven by the higher CAS 30-day (periprocedural) stroke rate.  The trial was criticized (by some) for including MI as a component of the primary outcome.  There was no significant difference between CAS and CEA in rates of restenosis or revascularization (Brott 2016).

Prespecified subgroup analysis found no significant between-group differences between symptomatic and asymptomatic patients (Silver 2011).  However, the trial was not powered to detect outcome differences in the asymptomatic population; thus, comparison between CAS and CEA specifically for asymptomatic patients with severe carotid stenosis and standard surgical risk remained hypothesis-generating. 

ACT-1

ACT-1 randomized 1,453 patients who were asymptomatic (i.e., had not had a stroke, transient ischemic attack, or amaurosis fugax in the 180 days before enrollment), with severe stenosis (≥70% by carotid ultrasound or angiography), and standard surgical risk, to CAS with an embolic protection device or to CEA.  While the trial had a short “run in” phase, there was no physician credentialing criteria as done in CREST.  The trial had planned for 1,658 patients but was stopped early due to slow enrollment and “not related to patient safety, futility, or concerns regarding the study devices” (Rosenfield 2016); hence the trial was slightly underpowered (landing at 75% power).  The primary and some secondary outcomes were also different from other trials.  The trial used a non-inferiority design[1] with a margin of 3% for the primary outcome (a composite of any death, stroke [ipsilateral or contralateral], or MI within 30 days of the procedure), or any ipsilateral stroke within 1 year (Rosenfield 2016).

The trial found, for the primary composite outcome, that CAS (at 3.8%) was noninferior to CEA (at 3.4%).  There was no significant difference, in the context of a non-inferior design, between CAS and CEA for:

• the composite of any stroke or death within 30 days (2.9% for CAS, 1.7% for CEA);
• the composite of major stroke or death within 30 days (0.6% for each);
• freedom of ipsilateral stroke from 30 days to 5 years after the procedure (97.8% for CAS, 97.3% for CEA);
• overall survival (87.1% for CAS, 89.4% for CEA); and
• the cumulative 5-year rate of stroke-free survival (93.1% for CAS, 94.7% for CEA).  (Rosenfield 2016.)

Within 30 days of the procedure, CAS had more strokes, while CEA had more MIs (but these were not statistically significant).  CEA had a small but statistically higher rate of cranial nerve palsies (1.1% vs 0.1% for CAS) (Rosenfield 2016).

Evidence gaps after CREST, ICSS, and ACT-1

An editorial on both CREST and ACT-1 (as these were published in the same issue of the NEJM) concluded that the question about the long-term durability of stents was now answered (Spence and Naylor 2016).  The editorial then highlighted remaining evidence gaps.

The first major gap was “the issue of the generalizability of randomized-trial findings into routine clinical practice . . .” Citing a recent systematic review (Paraskevas 2016), they stated that “9 of 21 large administrative data-set registries (43%) reported rates of death and stroke in excess of the 3% risk threshold that is recommended by the American Heart Association in asymptomatic patients undergoing stenting, as compared with 1 of 21 registries (5%) after endarterectomy” (Spence and Naylor 2016).

The second gap, and related to the issue of generalizability, was a question of appropriate patient selection in broad practice, specifically in the United States.  In the U.S., “more than 90% of carotid-artery interventions are performed in asymptomatic patients, even though evidence suggests that up to 90% of them will undergo an ultimately unnecessary and potentially harmful procedure [Bogiatzi 2012, Spence 2005].  By contrast, the percentage of interventions that are performed for asymptomatic stenoses is approximately 60% in Germany and Italy, 15% in Canada and Australia, and 0% in Denmark [Vikatmaa 2012]” (Spence and Naylor 2016).

The third gap, and related to appropriate selection of patients, was the question of whether any procedure was necessary for patients with carotid artery stenosis, particularly asymptomatic ones, given vast improvements in OMT since the foundational trials demonstrated the clinical utility of CEA over 30 years ago.  The editorial stated that “data from both randomized trials and nonrandomized studies suggest that the annual rate of stroke among medically treated asymptomatic patients has declined over the past two decades, regardless of the severity of stenosis at baseline [Naylor 2015].  Evidence now suggests that the annual rate of ipsilateral stroke may be as low as 0.5 to 1% [Naylor 2015] — a rate that is very similar to that observed in ACT I and CREST after successful stenting or endarterectomy [Rosenfield 2016, Brott 2016]” (Spence and Naylor 2016).

The editorial thus concluded: “Outside clinical trials, endarterectomy and stenting should be reserved for patients with symptomatic severe stenosis or for asymptomatic patients who are shown to be at higher risk for stroke with medical therapy than with intervention [Spence 2005, 2010; Markus 2010; Naylor 2014]” (Spence and Naylor 2016).

In sum, after the longer-term results of ICSS (2015) and CREST (2016), and the ACT-1 trial (2016), there was stronger evidence for CAS (compared to CEA, but not for either procedure compared to OMT) in symptomatic patients with standard surgical risk and carotid artery stenosis.

Although both ICSS and CREST included patients with carotid stenosis ≥50%, most patients (89% in ICSS, 86% in CREST) had stenosis ≥70%.  A secondary analysis of pooled data of symptomatic patients from these two trials (and including two prior trials) supported that rates for stroke recurrence for CAS and CEA were similar and low out to 10 years (Brott 2019), but given its design, this study is hypothesis-generating.  However, there is face value in the overall result for the primary outcome of a randomized controlled trial population.  While it is important to look at forest plots and other tools for subgroup analysis for indications of which patients in the trial benefitted more or less, caution must be taken in drawing conclusions from these.  That caution cuts both ways.  One cannot definitively reject or accept a certain subpopulation of a trial based on non-powered subgroup analysis.  Nor can one reject or accept a conclusion about a subpopulation based on analysis of data pooled with other trials; for each trial has greater validity internally within the randomized population sample, and less validity outside of it.  Such analyses are useful, but mostly for forming hypotheses.

More significant evidence gaps remained for asymptomatic patients (with CREST not powered for subgroup analysis of asymptomatics, and irregularities in the ACT-1 trial) and for generalizability of trial results to broader (“real-world”) community practice.  Viewing the randomized trials up to that time as a whole, there were limitations due to varying patient populations, interventionalists’ experience (e.g., CREST credentialed physicians while ACT-1 did not), primary outcomes, device types, and use of embolic protection devices.  Finally, comparison of these procedures to vastly improved, contemporary OMT was needed.

SPACE-2 and ACST-2 (contemporary trials, asymptomatic patients)

In 2022, CMS accepted a complete, formal request to reconsider this NCD, due to the new body of evidence available since the 2009 analysis.  In addition to the SPACE-2 trial (Reiff 2022), ACST-2, the most recent and also the largest of any CAS vs CEA trial, and designed to address key concerns about asymptomatic patients, had recently been published (Halliday 2021).  We consider these two the “contemporary” trials as background OMT, patient selection, and physician criteria were all improved from prior trials.

SPACE-2

SPACE-2 was designed as a three-armed RCT (BMT alone vs. CEA plus BMT vs. CAS plus BMT) in asymptomatic patients with moderate-to-severe carotid artery stenosis, ≥50% by NASCET trial criteria.  (Note that BMT or best medical therapy, is also called OMT or optimal medical therapy, throughout the literature.)  The primary outcome was “the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischemic stroke within 5 years” (Reiff 2022).

However, because of slow patient recruitment, the trial was changed to two parallel RCTs (BMT alone vs CEA and BMT, and BMT alone vs CAS and BMT).  The authors reported that “Trial recruitment ceased after recruiting 513 patients over a 5-year period (CEA vs. BMT (n=203); CAS vs. BMT (n=197), and BMT alone (n=113)).  The 30-day rate of any death or any stroke was 2.0% for patients undergoing CEA, and 2.5% for patients undergoing CAS.  No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT” (Reiff 2022).  Originally, the trial planned to include 3,640 patients.

At the 5-year mark, there was no significant difference among the three arms for the primary outcome (the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischemic stroke within 5 years), with 2.5% for CEA, 4.4% for CAS, and 3.1% for BMT (Reiff 2022).

The authors concluded that “CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period.  Because of the small sample size, results should be interpreted with caution.”

Explaining the recruitment problem, an editorial stated: “SPACE-2 concluded that recruitment largely failed because (1) many non-trial clinicians believed that interventions were warranted in the majority of asymptomatic patients; (2) patients expected to undergo CEA/CAS following referral and did not want to be randomized to BMT; (3) CAS was already reimbursed across the SPACE-2 countries for the treatment of asymptomatic patients outside the trial; and (4) randomization to BMT (which was not reimbursed) meant a loss of income to randomizing hospitals, surgeons, and interventionists” (Naylor 2016).

ACST-2

We discuss the ACST-2 trial in greater depth as it is both the largest, and the most recent, of any CAS vs CEA trial.  It fills a major evidence gap by doubling the total number of asymptomatic trial patients, and its results complement those of a recent large (“real-world”) registry study.

ACST-2 randomized 3,625 asymptomatic patients with severe carotid artery stenosis (97% of patients had stenosis ≥70% by duplex ultrasound) and standard surgical risk to CAS with embolic protection or CEA with outcome assessments at 30 days, 5 years, and 10 years. 

As with earlier trials, the terms “standard” or “average” risk were not used, but the description matched their meaning.  Duplex (Doppler vascular plus B mode) ultrasound became the dominant imaging modality, replacing interventional (catheter) angiography, because it is readily available, has improved in accuracy, and most importantly, is non-invasive; it was found that interventional angiography itself was associated with higher stroke risk (Naylor 2023, Halliday 2021).  Ultrasound stenosis was confirmed by CT or MR angiography (CTA or MRA); the latter provided additional anatomical information as well (e.g., aortic tortuosity, and plaque characteristics, length, and burden proximally and distally).  Physicians had to meet outcome criteria (a first in any trial): “For participation, the risks of any stroke or death had to be 6% or lower for symptomatic patients and 3% or lower for asymptomatic patients” (Halliday 2021).

The primary early outcome was a composite of disabling stroke or death from any cause at 30-days (i.e., procedure-related events).  The strength of this composite is that these two harms are important, relevant, and roughly equivalent (indeed many older Americans prefer death to a major, disabling stroke; CMS 2019).  The primary late outcome was “long-term (up to 5 or more years) prevention of stroke, particularly disabling or fatal stroke” (Halliday 2021).

Prespecified meta-analysis combining data on symptomatic and asymptotic patients across recent trials, including ACST-2, and comparison of ACST-2 trial results to those of a large registry, were performed with the aim of improving both subgroup analysis and generalizability to broad community practice.  Finally, the study sponsors “had no role in design, data collection, analysis, interpretation, or report writing” (Halliday 2021) – aimed at reassuring that this was an unbiased, investigator-led trial.  

The ACST-2 trial found, for early (30-day, procedural) outcomes, that 1% overall had disabling stroke or death (with no significant difference between CAS and CEA), while 2% had non-disabling stroke (with CAS having a statistically significant higher rate of 2.7% vs 1.6% for CEA).  CEA in turn had a greater number of MIs (0.7% CEA vs 0.3% CAS), which was not statistically significant, and of cranial nerve palsies (5.4% vs 0), which was.  This pattern of adverse events was consistent with prior trials, including those with symptomatic patients (e.g., Ederle 2010, Economopoulos 2011, Rosenfield 2016, Cui 2018).  The net crossover from CAS to CEA was 53 patients (3% of the CAS group); CAS unsuitability or failure was typically due to unfavorable anatomy (e.g., extensive arterial calcifications, or tortuosity of vessels including the aorta) (Halliday 2021).

For late outcomes, the 5-year non-procedural rates for fatal or disabling stroke was 2.5% (or 0.5% per year) for each procedure, and for any stroke, 5.3% for CAS and 4.5% for CEA (with no significant difference).  Patients are being followed for 10-year outcomes.  Meta-analysis evaluating any non-procedural stroke in all recent CAS vs CEA trials demonstrated no significant difference between symptomatic and asymptomatic patients (at their respective degrees of stenosis specified in trial inclusion criteria) (Halliday 2021).

The ACST-2 results are best viewed against the background of three facts.  The first was the relative lack of asymptomatic patients in prior trials comparing CAS to CEA (also noted in a 2012 Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) meeting).  ACST-2 has now doubled the number of total asymptomatic trial patients.

The second fact was the similar results of a German nationwide registry (IQTiG 2023), which found that “asymptomatic patients undergoing CAS [n=18,000] or CEA [n=86,000] during 2014–19 had in both cases an in-hospital risk of disabling stroke or death of 0.7%, with median time to discharge of 4–5 days3 (appendix p 9).  A risk of 0.7% within 4–5 days suggests a 30-day risk of disabling stroke or death of about 1% for each procedure” (Halliday 2021).  In addition, in-hospital non-disabling stroke was 1.1% for CAS and 0.7% for CEA (IQTiG 2023, Halliday 2021).

The third fact was the emergence of studies suggesting that with contemporary OMT alone, patients with severe carotid stenosis may have a risk of about 1% per year of disabling stroke or death (Naylor 2015, Halliday 2021, Reiff 2022).

The authors concluded, “The main finding from the ACST-2 trial of CAS versus CEA is that the effects of the two procedures on disabling or fatal events are approximately equal in terms of procedural hazards (about 1% for each treatment, in line with findings from large, representative registries) and of 5-year disabling stroke rates (which were about 0.5% per year with either procedure, suggesting that they would have been about 1% per year with neither procedure)” (Halliday 2021). 

Our conclusion: with the ACST-2 trial, there is now sufficient evidence for CAS (compared to CEA, but not for either procedure compared to OMT) in asymptomatic patients with standard as well as high surgical risk, and carotid artery stenosis ≥70%.

Recent systematic reviews and guidelines

Recent systematic reviews and meta-analyses (e.g., Hasan 2021, Howard 2021, Müller 2020, Galyfos 2019, Cui 2018) were written before ACST-2, and while helpful, are outdated with respect to treatment of asymptomatic patients with carotid artery disease.  The Oxford Vascular Study, a large prospective, population-based study in the UK, “aimed to establish whether there is any association between the degree of asymptomatic stenosis and ipsilateral stroke risk in patients on contemporary medical treatment” (Howard 2021).  The study included patients who were currently asymptomatic, but who were referred because of a “recent suspected transient ischaemic attack or stroke” – and as such reflected a slightly different population from those in the ACST-2 trial.

The Oxford study concluded that “the stroke risk reported in cohort studies was highly dependent on the degree of asymptomatic carotid stenosis, suggesting that the benefit of endarterectomy might be underestimated in patients with severe stenosis.  Conversely, the 5-year stroke risk was low for patients with moderate stenosis on contemporary medical treatment, calling into question any benefit from revascularisation” (Howard 2021).  This further supports the inclusion criteria in ACST-2 of patients with severe stenosis only.

The difference in findings about the relationship between the degree of carotid stenosis and risk of ipsilateral stroke in the ACST-2 trial (no relationship found), and the Oxford cohort study (a positive relationship found) is unclear but could be due in part to differences in patient populations as the Oxford patients were referred originally because of prior symptoms (neurological events).  However, both the Oxford and ACST-2 authors agree that it is unclear which patients may still benefit from any carotid artery procedure, compared to contemporary optimal medical therapy alone – and hence on the importance of ongoing trials (such as CREST-2 and ECST-2) which include OMT alone as a separate trial arm.

Recent guidelines, in turn, specifically the 2021 U.S. Society for Vascular Surgery (SVS), the 2021 European Stroke Organization (ESO), and the 2020 German-Austrian guidelines, recommend CEA (plus OMT) for asymptomatic patients with standard (average) surgical risk, and carotid stenosis ≥70% (AbuRahma 2022a, 2022b; Bonati 2021; Eckstein 2020).  None of these consider ACST-2 trial results, published later.  These societies also recommend that providers should have outcomes below certain thresholds for procedural disabling stroke or death (<2% in the 2020 German-Austrian and 2021 ESO, and <3% in the 2021 SVS and 2023 ESVS guidelines), and that patients have a reasonable life expectancy (>5 years typically, but not by every guideline).  The German-Austrian and ESO guidelines dropped to <2% rate of stroke/death from the previous threshold of <3% based on the lower rates seen in recent CAS vs CEA trials, and in recent observational studies of patients on OMT alone (Eckstein 2020, Bonati 2021).

U.S. Society for Vascular Surgery (SVS) Guidelines (AbuRahma 2022a, 2022b)

The SVS (U.S.) guideline has yet to be updated after the ASCT-2 trial publication.  The current guideline recommends the following:

• For neurologically symptomatic patients with stenosis less than 50% or asymptomatic patients with stenosis less than 60% diameter reduction, optimal medical therapy is indicated. There are no data to support transfemoral CAS, TCAR, or CEA in this patient group.
• Neurologically asymptomatic patients with a 70% or greater diameter stenosis should be considered for CEA, TCAR, or transfemoral CAS for reduction of long-term risk of stroke, provided the patient has a 3- to 5-year life expectancy and perioperative stroke/death rates can be 3% or less. Perhaps future models to help estimate life expectancy based on calculating various physiologic comorbidities such as cardiac, pulmonary, renal, malignancy, will be available in the future. The determination for which technique to use should be based on the presence or absence of high risk criteria for CEA, TCAR, or transfemoral CAS (Table I).  [Table I appears in-line below.]
• CEA is preferred over transfemoral CAS in symptomatic patients with 50% or greater stenosis who are candidates for both procedures. TCAR is preferred over transfemoral CAS but not CEA in symptomatic patients with 50% or greater stenosis.
• Transfemoral CAS is preferred over CEA in symptomatic patients with 50% or greater stenosis and tracheal stoma, situation where local tissues are scarred and fibrotic from prior ipsilateral surgery or external beam radiotherapy. CEA or TCAR may be preferable in situations where ipsilateral tissue planes remain relatively intact.
• TCAR is preferred over CEA and transfemoral CAS in symptomatic patients with 50% or greater stenosis and lesion above C2.
• TCAR is preferred over CEA and transfemoral CAS in high surgical risk (both anatomically and physiologically).
• CAS is preferred over CEA in symptomatic patients with 50% or greater stenosis and severe uncorrectable coronary artery disease, congestive heart failure, or chronic obstructive pulmonary disease. The committee recognized the difficulty in clearly defining this group of individuals, both in symptomatology and risk assessment, and acknowledged the potential increased role of aggressive medical management as primary therapy in this high-risk group.
• Neurologically asymptomatic patients deemed high risk for CEA, TCAR, and transfemoral CAS should be considered for primary medical management. Intervention can be considered in these patients only with evidence that perioperative morbidity and mortality is less than 3%. CAS should not be performed in these patients except as part of an ongoing clinical trial.
• There are insufficient data to recommend transfemoral CAS as primary therapy for neurologically asymptomatic patients with 70% to 99% diameter stenosis. Data from CREST, ACT, and the VQI suggest that in properly selected asymptomatic patients, CAS may be equivalent to CEA in the hands of experienced interventionalists. Operators and institutions performing CAS must exhibit expertise sufficient to meet the previously established AHA guidelines for treatment of patients with asymptomatic carotid stenosis. Specifically, the combined stroke and death rate must be less than 3% to ensure benefit for the patient.

Table I. Revascularization techniques with high-risk criteria

European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines(Naylor 2022)

The most recent of any societal guideline, the 2023 ESVS clinical guidelines recommends, for symptomatic patients: “for patients reporting carotid territory symptoms within the preceding six months” and who have either a 50-69%, or a 70-99%, carotid stenosis, “carotid endarterectomy is recommended provided the 30-day risk of death/stroke rate is <6%” (Naylor 2022).

For asymptomatic patients, the ESVS recommends that “for average surgical risk patients with an asymptomatic 60-99% stenosis, carotid endarterectomy should be considered,” while carotid stenting “may be an alternative to carotid endarterectomy,” in both cases “in the presence of one or more imaging or clinical characteristics that may be associated with an increased risk of late stroke, provided 30-day stroke/death rates are <3% and patient life expectancy exceeds five years” (Naylor 2022).  For asymptomatic patients “deemed by the multidisciplinary team to be ‘high risk for surgery’ and who have an asymptomatic 60-99% stenosis in the presence of one or more imaging/clinical characteristics that may be associated with an increased risk of late stroke on best medical therapy, carotid stenting may be considered provided anatomy is favourable, 30-day death/stroke rates are <3% and patient life expectancy exceeds five years” (Naylor 2022).

As for diagnostic work up and patient selection, ESVS recommends the following (Naylor 2022):

• For patients undergoing evaluation of the extent and severity of extracranial carotid stenoses, duplex ultrasound, computed tomographic angiography and/or magnetic resonance angiography are recommended.
• For a patient where carotid artery stenting is being considered, it is recommended that any duplex ultrasound study be followed by computed tomographic angiography or magnetic resonance angiography, which will provide additional information on the aortic arch, as well as the extra- and intracranial circulation.
• In units [centers] which base management decisions in patients with atherosclerotic carotid disease on duplex ultrasound measurement, it is recommended that reports should state which measurement method is used.
• For patients with atherosclerotic disease being considered for revascularisation, intra-arterial digital subtraction [catheter] angiography is not recommended, unless there are significant discrepancies on non-invasive imaging.
• Multidisciplinary team review is recommended to reach consensus decisions regarding the indications for, and treatment of, patients with carotid stenosis regarding carotid endarterectomy, carotid stenting or optimal medical therapy.
• Independent neurological assessment before and after carotid interventions is recommended to audit periprocedural risks.
• For patients with asymptomatic and symptomatic carotid disease, behavioural counselling to promote healthy diet, smoking cessation and physical activity is recommended.”  This is in addition to extensive ESVS recommendations on optimal medical therapy, which go beyond the scope of this NCD.

The ESVS states a preference for CEA over CAS (where the latter could include TCAR as well as transfemoral CAS) in symptomatic patients age >70yrs.

Considering Societal Guidelines and Trial Evidence as a Whole

As noted above, our coverage criteria for CAS – the focus of this NCD – is based primarily on the evidence from large RCTs, and thus on the major patient inclusion and exclusion criteria for these trials.  However, there is significant overlap among recommendations by SVS and ESVS, and the trial evidence itself (as might be expected), with some discrepancies, and we note that ACST-2 trial results for asymptomatic patients were not available for the SVS committee to consider when writing its recommendations.

No guideline (or any of the five new major RCT papers discussed above) recommends or provides evidentiary support for treatment with any procedure for any patient with carotid artery stenosis <50%.  All support OMT combined with lifestyle/behavioral modifications (and no procedure) in patients with mild stenosis as such, to prevent progression of carotid atherosclerotic disease.  The ESVS recommends independent neurological assessment before and after carotid interventions to assess procedural risks, and facilitate audits.  Our proposed decision reflects these recommendations.

We also agree that imaging should be non-invasive, with rare exceptions, as catheter angiography is associated with its own risk of stroke.  We derive our criteria for thresholds for carotid stenosis principally from the randomized trials themselves (as reviewed earlier), as these provide the primary evidence base.   Largely based on those trials, we concluded that there is sufficient, new RCT evidence for CAS to be considered for certain symptomatic patients, across the spectrum of patient risk for adverse events with CEA, with carotid artery stenosis ≥50%.  There is also sufficient evidence now for CAS to be considered for certain asymptomatic patients, also across the risk spectrum, with carotid artery stenosis ≥70%.  Hence, we propose to remove risk categories for symptomatic and asymptomatic patients from the 2009 NCD, and to update criteria for the degree of carotid stenosis required for each group.  We do not establish coverage criteria based on comparison of TCAR to CEA or transfemoral CAS, as CAS vs CEA have multiple RCTs for symptomatic and asymptomatic patients, while TCAR has none.  As we discuss in the TCAR section below, TCAR remains from a regulatory standpoint a type of CAS that uses a different delivery approach.  

If duplex ultrasound is the first-line imaging of carotid stenosis, CT or MR angiography should be performed also, primarily to provide “additional information on the aortic arch, as well as the extra- and intracranial circulation” (as the ESVS recommends, above).  This is important for determining which procedure – if any – is most suitable for the individual patient.  The more invasive imaging method of intra-arterial digital subtraction (catheter) angiography should be used only when there is significant discrepancy between non-invasive imaging results.  All imaging reports of stenosis should specify the method or criteria used (e.g., “NASCET criteria” for a direct measure of luminal stenosis, and for duplex ultrasound, the method for correlating metrics for peak-systolic velocity, etc., with degree of carotid stenosis).

In most clinical scenarios, we expect that duplex ultrasound will be the first-line imaging for patients being worked up for a possible carotid artery procedure.  Many of these imaging studies will be negative (meaning the patient may have carotid disease, but does not meet criteria for a procedure).  Those with a positive duplex ultrasound study would then receive either CT or MR angiography (for reasons discussed above, and as consistent with ESVS recommendations).  The findings from these imaging studies, along other patient characteristics (age, comorbidities), and patient concerns and preferences, are to be discussed in formal SDM.

We use the term “certain” symptomatic and asymptomatic patients above as there is a growing body of evidence about which patients might be better suited for the respective procedures (or OMT alone, with no procedure).  Contemporary risk stratification includes not just patient age and comorbidities (e.g., presence and severity of heart disease, lung disease, diabetes, hypertension, obesity, history of stroke or MI), which are typically assessed before any surgery, but also, for carotid procedures, relevant arterial anatomy, and characteristics, locations and extent of atherosclerotic plaques to include above and below the carotid bulb.

For example, a recent review states, “there are a variety of clinical and imaging features associated with the risk of future stroke in asymptomatic carotid stenosis. They include: (1) stenosis progression; (2) plaque characteristics including morphology, size, and vulnerability; (3) accompanied stroke-related conditions; and (4) microembolization” (Baek 2023).  However, the evidence on patient risk stratification is still growing and has not matured to the extent that would allow us to codify stable, evidence-based criteria into NCD coverage criteria at this time.

Individual patient characteristics thus matter, but so do patient concerns and preferences, especially as there are three management strategies (CAS, CEA, OMT alone), and the two procedures entail different procedural (30-day) risks (minor stokes generally being more common with CAS; MI and cranial nerve palsies, with CEA).  As a clinical example, a patient with no aortic tortuosity, good femoral access, no extensive carotid calcifications, no hypertension or significant white matter disease on brain MRI, but (stable) coronary artery disease, and whose father died in his 50s from an MI, might reasonably select CAS over CEA, other factors being equal.  A different patient with a different clinical picture and set of concerns may reasonably select CEA. Many patients will (and probably should) select OMT alone.

We agree with both of the SVS and ESVS (and all other) guidelines that asymptomatic patients should have some reasonable degree of life expectancy to overcome the procedural (30-day) risks of adverse events such as death, stroke, MI, and cranial nerve palsies demonstrated in multiple trials.  Most guidelines recommend >5 years, while the SVS (U.S.) recommends at least “3-5 years.”  We encourage continual updates to the criteria, as clinical outcomes improve (and adverse events decline), and acknowledge that there is currently no agreed-upon, evidence-based formula for determining life expectancy.  Life expectancy is to be a topic discussed in patient-doctor SDM.

Finally, we agree that provider criteria are important (physicians should only be doing a procedure if they can do it well), as reflected in both SVS and ESVS recommendations that only providers with demonstrated 30-day stroke/death rates <3% for asymptomatic patients (and <6% for symptomatic patients per the ESVS) should be doing a procedure (AbuRahma 2022a, 2022b; Naylor 2022).

However, we are not proposing specific physician, care team, or facility requirements in this NCD.  Large registries support the conclusion that benefits and harms of CAS compared to CEA seen in trials are generalizable to broad community practice.  This is not surprising, as twenty years have passed since the first IDE study was conducted for CAS.  The standard of care for diagnosis and treatment of carotid artery disease, and training to enter this field, has furthermore matured since our 2009 NCD reconsideration.  Provider and individual patient data are maintained at these local facilities, and team approaches to care and acceptable patient outcomes are backed by contemporary trials and guidelines alike.  Appropriate physician and facility experience and outcomes are adequately reflected in current standards of care, that data can be used for continuous quality improvement, and institutional processes (public and private) exist to monitor practice and enforce standards.  As such, we are proposing to discontinue the requirement that facilities meet specific standards and be approved by CMS to perform CAS procedures.

Also, the standards themselves are constantly improving.  For example, the current rate for procedural (30-day) disabling stroke or death in asymptomatic patients is now near 1%, and for any stroke or death, below 4% (for either procedure, in trials and registries alike).  The ESVS recommends that providers have a <3% rate for any stroke or death for asymptomatic patients (and <6% for symptomatic ones) – but hinted that this could change (Naylor 2022).  The SVS guidelines have yet to be updated after ACST-2.  We would not want to codify in an NCD a numeric threshold that may be constantly moving.  For these reasons, while we believe thresholds for provider outcomes are valuable, it is in part because societal guidelines continually (and appropriately) update them that we do not feel a need to include them as specific NCD coverage criteria at this time.

Transcarotid artery revascularization

Transcarotid artery revascularization (TCAR) is a hybrid procedure that combines elements of CAS and CEA.  A stent is placed in the carotid artery through a surgical incision, and cerebral protection is provided by proximal carotid artery clamping and reversal of cerebral arterial flow (these are combined in the ENROUTE Transcarotid Stent and Neuroprotection System).  TCAR was initially performed with a stent that had already been FDA-approved, a shorter version of the same stent used in the CAS arm of the CAS v CEA SAPPHIRE trial (Kashyap 2022).  As such, TCAR was regarded essentially as an approved stent using a different route and method of insertion compared to traditional CAS.  ROADSTER, a small observational study, was the first to use the ENROUTE transcarotid neuroprotection system (NPS), with a variety of carotid artery stents.  Promising 30-day results (Kwolek 2015), and 1-year follow-up of a subset of these patients (Malas 2019) led to the much larger ROADSTER 2 observational study, which used only the ENROUTE Transcarotid Stent and Neuroprotection System (Kashyap 2020, 2022).  This NCD remains consistent with the initial categorization of TCAR as a stent system.  We do not distinguish for purposes of coverage criteria, among different: approaches for deploying FDA-approved stent systems (eg, transfemoral, transradial, or transcarotid); types of FDA-approved stents (eg, open cell, closed cell, dual layer); or types of FDA-approved devices and methods for embolic protection (eg, proximal vs distal, use of blood flow reversal).

The Vascular Quality Initiative (VQI) registry reportedly captures 95% of all TCAR procedures performed in the U.S.  Scores of observational studies have analyzed data collected in this registry.  The registry is commendable and valuable due to its size (>15,500 patients as of 2022), diversity (21% of registry participants are Black, although only 8% are Hispanic), and degree of standardization (Zhang 2022).

Using the registry platform, the ROADSTER 2 prospective observational study included 632 patients at high risk for adverse events with CEA, with symptomatic carotid artery stenosis ≥50%, or asymptomatic stenosis ≥80%.  Early (30-day, periprocedural) outcomes demonstrated a “composite 30-day stroke/death rate of 0.8% and a stroke/death/myocardial infarction (MI) rate of 1.7%” using per-protocol, not intention-to-treat, statistical analysis (Kashyap 2020).  One-year follow up of a small subset of 155 of those ROADSTER 2 patients reported no subsequent ipsilateral stroke (post-procedural, so between 31and 365 days), although 4 patients (2.6%) died, all deemed to be due to non-neurological causes (Kashyap 2022).

A recent retrospective cohort study using propensity-score methods matched 2,962 TCAR patients with standard surgical risk, “defined as those lacking Medicare-defined high medical or surgical risk characteristics,” with similar CEA patients in a 1:3 ratio (Liang 2023).  The study found no statistically significant difference in the risk of the primary composite outcome of 30-day stroke, death, or MI or 1-year ipsilateral stroke (TCAR 3.0%; CEA 2.6%).  TCAR was associated with a statistically significant higher risk of 1-year ipsilateral stroke (TCAR 1.6%; CEA 1.1%), but no difference in 1-year all-cause mortality (Liang 2023).  An accompanying editorial commented that “an important caveat is the completeness of data at 1 year was poor with only 33% of patients who underwent TCAR with available information and 50% of patients who underwent CEA” (Chaturvedi 2023).

The totality of evidence demonstrates that TCAR is promising as a suitable alternative for certain patients in need of carotid artery revascularization.  There is however the caveat that not a single pivotal RCT assessing TCAR has been performed, limiting its comparison to CEA or transfemoral CAS, which in contrast are supported by multiple contemporary randomized trials.  The authors of ROADSTER 2 concluded that “Larger, randomized controlled trials are needed to confirm the safety and efficacy of TCAR, as well as understand the comparative effectiveness with other carotid interventions” (Kashyap 2022).  We agree.  We also believe that pending CAS or CEA vs OMT trials (e.g., CREST-2 and ECST-2) may better inform patient risk stratification for all carotid artery procedures, TCAR included.

Ongoing trials comparing carotid procedures to OMT

“As with many procedures in the elderly, the key question is should it be done and not whether it can be done” (CMS 2009).

Based on marked improvement in OMT for patients with atherosclerotic disease over the last dozen years (as discussed earlier), two ongoing RCTs are designed to reassess the foundational trials, launched three decades ago, comparing revascularization (now with CEA or CAS) to contemporary OMT.

ECST-2

The 2nd European Carotid Surgery Trial (ECST‑2) is randomizing 2,000 patients with asymptomatic or symptomatic carotid stenosis ≥50% and an estimated 5-year risk of stroke of <20% using the Carotid Artery Risk (CAR) score, to revascularization (CEA or CAS, whichever is deemed most appropriate for the patient) or to OMT.  The primary outcome is the combined 2-year rate of any clinically manifest stroke, new cerebral infarct on MRI, MI or periprocedural death (Cheng 2022).

The CAR score was adapted from Rothwell’s model, developed from ECST trial data and validated with NASCET trial data, which showed that several factors such as carotid plaque ulceration, age and associated comorbidities could stratify patients into low, intermediate or high risk of future stroke in patients treated with medical therapy alone and also the amount of risk reduction through CEA (Rothwell 2005, Cheng 2022).  This is especially important given marked improvements in contemporary OMT using cholesterol-lowering statin, antihypertensive, and antithrombotic (anticoagulation and antiplatelet) medications, as well as behavioral modification (e.g., diet, exercise, smoking cessation).  The trial is estimated to be completed in early 2025.

CREST-2

Carotid revascularization for primary prevention of stroke (CREST-2) is two independent randomized controlled trials (CEA v OMT, and CAS v OMT) in 2,480 patients with asymptomatic carotid stenosis ≥70%.  The primary outcome is the composite of stroke and death within 44 days after randomization and ipsilateral stroke thereafter up to 4 years.  Intensive medical therapy is used in all arms, including medical and lifestyle modification and treatment for stroke risk factors such as hypertension, elevated cholesterol, diabetes, tobacco use, excess body weight, and sedentary lifestyle, with use of a patient coach.  The trial is estimated to be completed in early 2026.  There is a parallel CREST-2 registry designed in part to answer questions about generalizability.  (Turan 2020, 2012; Mott 2017; ClinicalTrials.gov accessed April 2023.)

Shared Decision-Making

As noted above, appropriate patient selection is critical to ensure optimal outcomes from CAS or any other treatment for carotid artery stenosis.  Individual patient characteristics, along with patient preferences, are important to consider when assessing treatment options.  Because there are multiple treatment options for carotid artery stenosis and patient characteristics are complex and varied in this space, it is essential that patients are informed of all treatment options and corresponding risks and benefits.  This is critical to ensure that not only are treatment options assessed to achieve optimal clinical outcomes, but beneficiary preferences and priorities are also incorporated in the decision-making process.

As such, we are proposing that prior to furnishing CAS, practitioners must engage in a formal shared decision-making (SDM) interaction with the beneficiary (to also include family and/or medical representatives as needed) using a validated, evidence-based tool to ensure the beneficiary is familiar with and aware of all treatment options including, but not limited to, the procedures that fall within the parameters of this NCD (i.e., traditional CAS and TCAR).  While we understand, at the time of writing, there is no validated, evidence-based SDM tool for any carotid artery procedure, we believe there is a distinct need for such a tool in light of the multiple treatment options, patient characteristic variability, and lack of consensus across medical specialties as to which treatment is best for which patients.

We are proposing that the formal SDM interaction must involve use of a validated SDM tool and include:

• Discussion of all treatment options for carotid stenosis to ensure the beneficiary is familiar with and aware of all treatment options including, but not limited to, procedures that fall within the parameters of this NCD.
• Explanation of risks and benefits for each option specific to the beneficiary’s clinical condition.
• Integration of clinical guidelines (e.g., patient life-expectancy).
• Discussion and incorporation of beneficiary’s personal preferences and priorities in choosing a treatment plan.

While CMS is not specifying how to develop an SDM tool (leaving this to clinical societies and other expert bodies), we believe the following criteria are informative:

“These criteria include: 1) transparency regarding the development and validation process (including availability of documentation of how development occurred, when updates were made, and any conflicts of interest within the development team); 2) direct relevance to the specific clinical decision patients are facing; 3) comprehensiveness of the discussion of available treatment options (including alternative pharmacomedical interventions and symptom-focused therapy where applicable); and 4) availability within the public domain” (Knopke 2019).

Additionally, when appropriate, the SDM interaction could offer information and recommendations from experts across specialties (for example from surgeons and non-surgical interventionalists) who perform procedures in accordance with contemporary standards of care as well as independent physicians with expertise in medical management of carotid artery disease. The goal of this type of interaction is to ensure beneficiaries have all relevant information and expert viewpoints to help them make an informed choice.  We are not proposing to require distinct interactions with each of these types of practitioners for coverage purposes, but strongly encourage a multidisciplinary approach to the diagnosis and treatment of this patient population (consistent with ESVS recommendations).

CMS is requesting comments on whether the SDM interaction should require the use of a validated SDM tool and/or if there are other options to achieve the goal of truly informed decision-making.

Health Disparities

We have stated that our NCD analysis considers the key randomized controlled trials (RCTs) as the strongest evidence base, but views these results through the prism of large registry data (which provide greater generalizability), recent guidelines from medical societies, and meta-analyses, systematic reviews, secondary analyses and the like.  On race and ethnicity, participation in trials of carotid artery disease treatments (and in all trials across all of medicine for that matter) has typically not reflected what the Medicare population ‘looks like’, and even if it did so, such ‘proportionate representation’ would generally not provide the subgroup sample sizes needed for definitive subgroup analysis.

While we strongly encourage better strategies for recruitment and retention of underrepresented populations in clinical trials, we have also not wanted that shortfall to itself create more barriers to access.  Thus, in practice, if there is no other evidence suggesting that a particular subgroup defined by race, ethnicity, or gender would not achieve meaningful clinical benefit from a treatment that shows overall positive results in a well-designed trial, our approach is to provide access to those subgroups.  We may encourage or require more research, but will err on the side of access for interventions which for the overall trial population result in meaningful, improved net health outcomes.

We take that approach – ‘leaning toward access’ – in this NCD, while acknowledging that the peer-reviewed medical literature (beyond the trials themselves) has reported differences in patients undergoing carotid revascularization and outcomes across race, ethnicity, gender, and insurance status.  We discuss some key studies in that literature below.

A retrospective analysis of State Inpatient Databases (SIDs) from five U.S. states assessed disparities across race and insurance status in postoperative outcomes of carotid revascularization (CEA or CAS) (Panchap 2020).  The authors found that Black and Hispanic patients had higher odds of stroke and combined death/stroke than White patients.  This disparity was also observed for a combined group of patients reported as having other non-White races. Black and other non-White patients also had increased odds of in-hospital mortality.  These disparities were observed after stratification by procedure type (CEA vs. CAS) and by symptoms on presentation (symptomatic vs. asymptomatic).  The authors reported that Black, Hispanic, and other non-White patients were more likely to undergo CAS than CEA.  The authors found that insurance status was not significantly associated with outcomes in this study.

A recent retrospective analysis of data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) assessed racial disparities in perioperative outcomes of CEA and CAS (Cui 2022).  The authors compared outcomes between White patients and a combined group of patients who were American Indian or Alaskan Native, Asian, Black or African American, or Native Hawaiian or Pacific Islander.  The authors found non-White patients were more likely than White patients to experience 30-day postoperative stroke, unplanned return to the operating room, and restenosis following carotid revascularization.  In a stratified analysis of CAS procedures, non-White patients had increased odds of postoperative stroke, stroke/death, and stroke/transient ischemic attack.  This disparity was not observed in a stratified analysis of CEA, but the authors found that non-White patients had increased odds of unplanned return to the operating room and restenosis.  The authors reported that non-White patients had fewer risk factors for CEA but were more likely to undergo CAS.

An analysis of data from self-referred, self-paid vascular screening assessments showed that Black and Hispanic participants had a more adverse cardiovascular risk profile, including a higher prevalence of hypertension or diabetes, but a lower prevalence of high-grade carotid stenosis than White participants (Lal 2021).  The authors also found that Asian participants had a generally lower prevalence of high-grade stenosis and participants reported as Native American had a higher prevalence of high-grade stenosis.  The authors concluded that a lower prevalence of high-grade carotid stenosis may contribute to the lower rates of carotid revascularization in Black and Hispanic patients in the United States.

A recent systematic review and meta-analysis of RCTs and observational studies showed that Black and Hispanic patients who underwent surgery for carotid artery stenosis were more likely symptomatic and had an increased risk for all-cause mortality and stroke or transient ischemic attack compared to White patients (Lee 2023).

A retrospective analysis of data from the Society for Vascular Surgery Vascular Quality Initiative (VQI) assessed sex-based disparities in outcomes following carotid revascularization (CEA or CAS) (Dansey 2020).  The authors found that among symptomatic patients who underwent CEA, female patients had increased odds of 30-day perioperative mortality compared to male patients. Among asymptomatic patients who underwent CAS, female patients had increased odds of in-hospital stroke and perioperative stroke/death.  The authors observed that female patients were less likely than male patients to receive perioperative statin and antiplatelet therapy.

A recent retrospective analysis of data from NSQIP assessed gender-based differences in postoperative complications of carotid intervention (CEA or CAS) (Goicoechea 2022).  The authors found that female gender was associated with a higher rate of 30-day postoperative cerebrovascular accident/stroke, bleeding complication, and urinary tract infection.  In asymptomatic patients, female gender was also associated with a higher rate of readmission.  In an analysis specific to CAS, the authors found that female gender was associated with higher odds of readmission and urinary tract infection. The majority of patients in this study (98.0%) underwent carotid endarterectomy.

A recent retrospective analysis of data from the National Inpatient Sample (NIS) assessed disparities across race and insurance status in the utilization of high-volume centers for carotid revascularization (Mabeza 2022).  The authors also assessed differences in clinical outcomes between high-volume and low-volume centers.  High-volume centers were hospitals in the highest quartile of annual carotid revascularization caseload (combined CEA and CAS); low-volume centers were in the lowest quartile of annual caseload.  The authors found that Black and Hispanic patients had lower odds of carotid revascularization at high-volume centers than White patients.  This disparity was also observed for a combined group of patients reported as Asian, Pacific Islander, Native American, and other races.  The authors reported that patients with Medicaid or no insurance were less likely to undergo carotid revascularization at high-volume centers than patients with private insurance.  The authors also found that high-volume centers were associated with lower odds of in-hospital mortality/stroke/MI than low-volume centers.  In an analysis specific to CAS, the authors found no significant differences in mortality/stroke/MI between high-CAS and low-CAS centers.  TCAR was not captured in this study.

Differences in health literacy, socioeconomic status, timely surgical access, physician referral patterns, provider factors, and institutional barriers have been suggested in the literature as potential contributors to the observed health disparities.  Further research is required to describe other circumstances and patient characteristics that may impede the delivery of carotid revascularization to those who can benefit from it.  CMS believes the expansion of coverage for CAS to our beneficiaries will serve to allow greater numbers of individuals to access this procedure for stroke prevention.

X.   Conclusion

The Centers for Medicare & Medicaid Services (CMS) proposes that coverage of percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting is reasonable and necessary with the placement of a Food and Drug Administration (FDA) approved carotid stent with an FDA-approved or cleared embolic protection device, for Medicare beneficiaries under the following conditions:

1. Patients with symptomatic carotid artery stenosis ≥50%; and
2. Patients with asymptomatic carotid artery stenosis ≥70%.  

For both A and B above:
1. Independent neurological assessment before and after carotid artery stenting (CAS) must be performed to assess procedural risks.
2. Evaluation of the extent and severity of carotid artery stenosis must use one of the following non-invasive modalities for first-line imaging: duplex ultrasound, computed tomography angiography, or magnetic resonance angiography.
   1. If duplex ultrasound is used as first-line imaging, computed tomography angiography or magnetic resonance angiography must also be performed to provide additional information about the aortic arch, and extra- and intra-cranial circulation, for better patient selection.
   2.  If either computed tomography angiography or magnetic resonance angiography is used as first-line imaging, no second-line imaging is required.
   3. Intra-arterial digital subtraction (catheter) angiography must not be used for first-line imaging, and may be used only when there is significant discrepancy between non-invasive imaging results.

Prior to furnishing CAS, the practitioner must engage in a formal shared decision-making interaction with the beneficiary. The shared decision-making interaction must involve the use of a validated shared decision-making tool and include:

• Discussion of all treatment options for carotid stenosis to ensure the beneficiary is familiar with and aware of all treatment options including, but not limited to, procedures that fall within the parameters of this NCD.
• Explanation of risks and benefits for each option specific to the beneficiary’s clinical condition.
• Integration of clinical guidelines (e.g., patient life-expectancy).
• Discussion and incorporation of beneficiary’s personal preferences and priorities in choosing a treatment plan.

In addition to the national coverage described above, Medicare Administrative Contractors (MACs) may make reasonable and necessary determinations under section 1862(a)(1)(A) for any other beneficiary seeking coverage for PTA of the carotid artery concurrent with stenting.

See Appendix B for the proposed manual language.

APPENDIX A

General Methodological Principles of Study Design
(Section VI of the Decision Memorandum)

When making national coverage determinations, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service is reasonable and necessary. The overall objective for the critical appraisal of the evidence is to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for patients.

We divide the assessment of clinical evidence into three stages: 1) the quality of the individual studies; 2) the generalizability of findings from individual studies to the Medicare population; and 3) overarching conclusions that can be drawn from the body of the evidence on the direction and magnitude of the intervention’s potential risks and benefits.

The methodological principles described below represent a broad discussion of the issues we consider when reviewing clinical evidence. However, it should be noted that each coverage determination has its unique methodological aspects.

Assessing Individual Studies

Methodologists have developed criteria to determine weaknesses and strengths of clinical research. Strength of evidence generally refers to: 1) the scientific validity underlying study findings regarding causal relationships between health care interventions and health outcomes; and 2) the reduction of bias. In general, some of the methodological attributes associated with stronger evidence include those listed below:

• Use of randomization (allocation of patients to either intervention or control group) in order to minimize bias.
• Use of contemporaneous control groups (rather than historical controls) in order to ensure comparability between the intervention and control groups.
• Prospective (rather than retrospective) studies to ensure a more thorough and systematical assessment of factors related to outcomes.
• Larger sample sizes in studies to demonstrate both statistically significant as well as clinically significant outcomes that can be extrapolated to the Medicare population. Sample size should be large enough to make chance an unlikely explanation for what was found.
• Masking (blinding) to ensure patients and investigators do not know to that group patients were assigned (intervention or control). This is important especially in subjective outcomes, such as pain or quality of life, where enthusiasm and psychological factors may lead to an improved perceived outcome by either the patient or assessor.

Regardless of whether the design of a study is a randomized controlled trial, a non-randomized controlled trial, a cohort study or a case-control study, the primary criterion for methodological strength or quality is to the extent that differences between intervention and control groups can be attributed to the intervention studied. This is known as internal validity. Various types of bias can undermine internal validity. These include:

• Different characteristics between patients participating and those theoretically eligible for study but not participating (selection bias).
• Co-interventions or provision of care apart from the intervention under evaluation (performance bias).
• Differential assessment of outcome (detection bias).
• Occurrence and reporting of patients who do not complete the study (attrition bias).

In principle, rankings of research design have been based on the ability of each study design category to minimize these biases. A randomized controlled trial minimizes systematic bias (in theory) by selecting a sample of participants from a particular population and allocating them randomly to the intervention and control groups. Thus, in general, randomized controlled studies have been typically assigned the greatest strength, followed by non-randomized clinical trials and controlled observational studies. The design, conduct and analysis of trials are important factors as well. For example, a well-designed and conducted observational study with a large sample size may provide stronger evidence than a poorly designed and conducted randomized controlled trial with a small sample size. The following is a representative list of study designs (some of that have alternative names) ranked from most to least methodologically rigorous in their potential ability to minimize systematic bias:

Randomized controlled trials
Non-randomized controlled trials
Prospective cohort studies
Retrospective case control studies
Cross-sectional studies
Surveillance studies (e. g. , using registries or surveys)
Consecutive case series
Single case reports

When there are merely associations but not causal relationships between a study’s variables and outcomes, it is important not to draw causal inferences. Confounding refers to independent variables that systematically vary with the causal variable. This distorts measurement of the outcome of interest because its effect size is mixed with the effects of other extraneous factors. For observational, and in some cases randomized controlled trials, the method in that confounding factors are handled (either through stratification or appropriate statistical modeling) are of particular concern. For example, in order to interpret and generalize conclusions to our population of Medicare patients, it may be necessary for studies to match or stratify their intervention and control groups by patient age or co-morbidities.

Methodological strength is, therefore, a multidimensional concept that relates to the design, implementation and analysis of a clinical study. In addition, thorough documentation of the conduct of the research, particularly study selection criteria, rate of attrition and process for data collection, is essential for CMS to adequately assess and consider the evidence.

Generalizability of Clinical Evidence to the Medicare Population

The applicability of the results of a study to other populations, settings, treatment regimens and outcomes assessed is known as external validity. Even well-designed and well-conducted trials may not supply the evidence needed if the results of a study are not applicable to the Medicare population. Evidence that provides accurate information about a population or setting not well represented in the Medicare program would be considered but would suffer from limited generalizability.

The extent to that the results of a trial are applicable to other circumstances is often a matter of judgment that depends on specific study characteristics, primarily the patient population studied (age, sex, severity of disease and presence of co-morbidities) and the care setting (primary to tertiary level of care, as well as the experience and specialization of the care provider). Additional relevant variables are treatment regimens (dosage, timing and route of administration), co-interventions or concomitant therapies, and type of outcome and length of follow-up.

The level of care and the experience of the providers in the study are other crucial elements in assessing a study’s external validity. Trial participants in an academic medical center may receive more or different attention than is typically available in non-tertiary settings. For example, an investigator’s lengthy and detailed explanations of the potential benefits of the intervention and/or the use of new equipment provided to the academic center by the study sponsor may raise doubts about the applicability of study findings to community practice.

Given the evidence available in the research literature, some degree of generalization about an intervention’s potential benefits and harms is invariably required in making coverage determinations for the Medicare population. Conditions that assist us in making reasonable generalizations are biologic plausibility, similarities between the populations studied and Medicare patients (age, sex, ethnicity and clinical presentation) and similarities of the intervention studied to those that would be routinely available in community practice.

A study’s selected outcomes are an important consideration in generalizing available clinical evidence to Medicare coverage determinations. One of the goals of our determination process is to assess health outcomes. These outcomes include resultant risks and benefits such as increased or decreased morbidity and mortality. In order to make this determination, it is often necessary to evaluate whether the strength of the evidence is adequate to draw conclusions about the direction and magnitude of each individual outcome relevant to the intervention under study. In addition, it is important that an intervention’s benefits are clinically significant and durable, rather than marginal or short-lived. Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits.

If key health outcomes have not been studied or the direction of clinical effect is inconclusive, we may also evaluate the strength and adequacy of indirect evidence linking intermediate or surrogate outcomes to our outcomes of interest.

Assessing the Relative Magnitude of Risks and Benefits

Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits. Health outcomes are one of several considerations in determining whether an item or service is reasonable and necessary. CMS places greater emphasis on health outcomes actually experienced by patients, such as quality of life, functional status, duration of disability, morbidity and mortality, and less emphasis on outcomes that patients do not directly experience, such as intermediate outcomes, surrogate outcomes, and laboratory or radiographic responses. The direction, magnitude, and consistency of the risks and benefits across studies are also important considerations. Based on the analysis of the strength of the evidence, CMS assesses the relative magnitude of an intervention or technology’s benefits and risk of harm to Medicare beneficiaries.

20.7 - Percutaneous Transluminal Angioplasty (PTA) (Various Effective Dates Below)

A. General 

This procedure involves inserting a balloon catheter into a narrow or occluded blood vessel to recanalize and dilate the vessel by inflating the balloon.  The objective of percutaneous transluminal angioplasty (PTA) is to improve the blood flow through the diseased segment of a vessel so that vessel patency is increased and embolization is decreased.  With the development and use of balloon angioplasty for treatment of atherosclerotic and other vascular stenoses, PTA with and without the placement of a stent) is a widely used technique for dilating lesions of peripheral, renal, and coronary arteries.

Indications and Limitations of Coverage 

B. Nationally Covered Indications 

The PTA is covered when used under the following conditions:

1. Treatment of Atherosclerotic Obstructive Lesions 

-In the lower extremities, i.e., the iliac, femoral, and popliteal arteries, or in the upper extremities, i.e., the innominate, subclavian, axillary, and brachial arteries. The upper extremities do not include head or neck vessels.

-Of a single coronary artery for patients for whom the likely alternative treatment is coronary bypass surgery and who exhibit the following characteristics: 

• Angina refractory to optimal medical management; 
• Objective evidence of myocardial ischemia; and
• Lesions amenable to angioplasty.  

-Of the renal arteries for patients in whom there is an inadequate response to a thorough medical management of symptoms and for whom surgery is the likely alternative. PTA for this group of patients is an alternative to surgery, not simply an addition to medical management.  

-Of arteriovenous dialysis fistulas and grafts when performed through either a venous or arterial approach.

2. 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. 

3. 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 and an FDA-approved or –cleared embolic protection device (effective December 9, 2009) for an FDA-approved indication when furnished in accordance with FDA-approved protocols governing post-approval studies. The Centers for Medicare & Medicaid Services (CMS) determines that coverage of PTA of the carotid artery is reasonable and necessary in these circumstances.

4. Concurrent with Carotid Stent Placement

5. Concurrent with Intracranial Stent Placement in FDA-Approved Category B IDE Clinical Trials 

Effective November 6, 2006, Medicare covers PTA and stenting of intracranial arteries for the treatment of cerebral artery stenosis ≥50% in patients with intracranial atherosclerotic disease when furnished in accordance with the FDA-approved protocols governing Category B IDE clinical trials.  CMS determines that coverage of intracranial PTA and stenting is reasonable and necessary under these circumstances. 

C. Nationally Non-Covered Indications 

All other indications for PTA with or without stenting to treat obstructive lesions of the vertebral and cerebral arteries remain non-covered. 

All other indications for PTA without stenting for which CMS has not specifically indicated coverage remain non-covered.

D. Other 

Coverage of PTA with stenting not specifically addressed or discussed in this NCD is at the discretion of the MACs. 

(This NCD last reviewed xx/xx/xx.)

APPENDIX C—NCD 20.7 (2009)

20.7 - Percutaneous Transluminal Angioplasty (PTA) (Various Effective Dates Below) (Rev. 212, Issued: 01-19-19, Effective: 02-19-19, Implementation: 02-19-19) 

The term Medicare beneficiary identifier (Mbi) is a general term describing a beneficiary’s Medicare identification number. For purposes of this manual, Medicare beneficiary identifier references both the Health Insurance Claim Number (HICN) and the Medicare Beneficiary Identifier (MBI) during the new Medicare card transition period and after for certain business areas that will continue to use the HICN as part of their processes.

A. General 

This procedure involves inserting a balloon catheter into a narrow or occluded blood vessel to recanalize and dilate the vessel by inflating the balloon.  The objective of percutaneous transluminal angioplasty (PTA) is to improve the blood flow through the diseased segment of a vessel so that vessel patency is increased and embolization is decreased.  With the development and use of balloon angioplasty for treatment of atherosclerotic and other vascular stenoses, PTA (with and without the placement of a stent) is a widely used technique for dilating lesions of peripheral, renal, and coronary arteries.

Indications and Limitations of Coverage 

B. Nationally Covered Indications 

The PTA is covered when used under the following conditions:

1. Treatment of Atherosclerotic Obstructive Lesions 

-In the lower extremities, i.e., the iliac, femoral, and popliteal arteries, or in the upper extremities, i.e., the innominate, subclavian, axillary, and brachial arteries. The upper extremities do not include head or neck vessels. 

-Of a single coronary artery for patients for whom the likely alternative treatment is coronary bypass surgery and who exhibit the following characteristics: 

The letter must include the following information:

• Facility's name and complete address; 
• Facility's national provider identifier (formerly referred to as the Medicare provider number);
• Point-of-contact for questions with telephone number;
• Discussion of how each standard has been met by the hospital;
• Mechanism of data collection of CAS procedures; and, 
• Signature of a senior facility administrative official.  

A list of certified facilities will be made available and viewable at: http://www.cms.hhs.gov/coverage/carotid-stent-facilities.asp.  In addition, CMS will publish a list of approved facilities in the Federal Register.

Facilities must recertify every two (2) years in order to maintain Medicare coverage of CAS procedures. Recertification will occur when the facility documents that and describes how it continues to meet the CMS standards.

The process for recertification is as follows:

1. At 23 months after initial certification: 
   • Submission of a letter to CMS stating how the facility continues to meet the minimum facility standards as listed above. 
2. At 27 months after initial certification: 
   • Submission of required data elements for all CAS procedures performed on patients during the previous two (2) years of certification.  

     Data elements:

     1. Patients’ Medicare beneficiary identifier if a Medicare beneficiary;
     2. Patients’ date of birth;
     3. Date of procedure;
     4. Does the patient meet high surgical risk criteria (defined below)? 
        • Age ≥80;
        • Recent (<30 days) MI;
        • LVEF <30%;
        • Contralateral carotid occlusion;
        • New York Heart Association (NYHA) Class III or IV congestive heart failure;
        • Unstable angina: Canadian Cardiovascular Society (CCS) Class III/IV;
        • Renal failure: end-stage renal disease on dialysis;
        • Common Carotid Artery (CCA) lesion(s) below clavicle;
        • Severe chronic lung disease; ○ Previous neck radiation;
        • High cervical Internal Carotid Artery (ICA) lesion(s);
        • Restenosis of prior CEA;
        • Tracheostomy;
        • Contralateral laryngeal nerve palsy. 
     5. Is the patient symptomatic (defined below)? 
        • Carotid Transient Ischemic Attack (TIA) persisting less than 24 hours;
        • Non-disabling stroke: Modified Rankin Scale
        • Transient monocular blindness: amaurosis fugax. 
     6. Modified Rankin Scale score if the patient experienced a stroke.
     7. Percent of stenosis of stented lesion(s) by angiography.
     8. Was embolic protection used?
     9. Were there any complications during hospitalization (defined below)? 
        • All stroke: an ischemic neurologic deficit that persisted more than 24 hours;
        • MI;
        • All death. 

Recertification is effective for two (2) additional years during which facilities will be required to submit the requested data every April 1 and October 1.

The CMS will consider the approval of national CAS registries that provide CMS with a comprehensive overview of the registry and its capabilities, and the manner in which the registry meets CMS data collection and evaluation requirements. Specific standards for CMS approval are listed below. Facilities enrolled in a CMS-approved national CAS registry will automatically meet the data collection standards required for initial and continued facility certification. Hospitals’ contracts with an approved registry may include authority for the registry to submit required data to CMS for the hospital. A list of approved registries will be available on the CMS Coverage Web site.

National Registries 

As noted above, CMS will approve national registries developed by professional societies and other organizations and allow these entities to collect and submit data to CMS on behalf of participating facilities to meet facility certification and recertification requirements. To be eligible to perform these functions and become a CMS-approved registry, the national registry, at a minimum, must be able to: 

1. Enroll facilities in every U.S. state and territory;
2. Assure data confidentiality and compliance with HIPPA;
3. Collect the required CMS data elements as listed in the above section;
4. Assure data quality and data completeness;
5. Address deficiencies in the facility data collection, quality, and submission;
6. Validate the data submitted by facilities as needed;
7. Track long term outcomes such as stroke and death;
8. Conduct data analyses and produce facility specific data reports and summaries;
9. Submit data to CMS on behalf of the individual facilities; and
10. Provide quarterly reports to CMS on facilities that do not meet or no longer meet the CMS facility certification and recertification requirements pertaining to data collection and analysis. 

Registries wishing to receive this designation from CMS must submit evidence that they meet or exceed our standards.  Though the registry requirements pertain to CAS, CMS strongly encourages all national registries to establish a similar mechanism to collect comparable data on CEA.  Having both CAS and CEA data will help answer questions about carotid revascularization, in general, in the Medicare population.

The CAS for patients who are not at high risk for CEA remains covered only in FDAapproved Category B IDE clinical trials under 42 CFR 405.201.

The CMS has determined that PTA of the carotid artery concurrent with the placement of an FDA-approved carotid stent and an FDA-approved or –cleared embolic protection device is not reasonable and necessary for all other patients.

5. Concurrent with Intracranial Stent Placement in FDA-Approved Category B IDE Clinical Trials 

Effective November 6, 2006, Medicare covers PTA and stenting of intracranial arteries for the treatment of cerebral artery stenosis ≥50% in patients with intracranial atherosclerotic disease when furnished in accordance with the FDA-approved protocols governing Category B IDE clinical trials.  CMS determines that coverage of intracranial PTA and stenting is reasonable and necessary under these circumstances. 

C. Nationally Non-Covered Indications 

All other indications for PTA with or without stenting to treat obstructive lesions of the vertebral and cerebral arteries remain non-covered. 

All other indications for PTA without stenting for which CMS has not specifically indicated coverage remain non-covered.

D. Other 

Coverage of PTA with stenting not specifically addressed or discussed in this NCD is at local A/B MAC discretion. 

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