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

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The Centers for Medicare and Medicaid Services (CMS) has determined, based on the Food and Drug Administration (FDA) clearance of new embolic protection devices, to revise the national coverage determination (NCD) language regarding embolic protection devices as follows in section B3 and B4 of the NCD: 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 for an FDA-approved indication when furnished in accordance with FDA-approved protocols governing post-approval studies. CMS determines that coverage of PTA of the carotid artery is reasonable and necessary in these circumstances. Medicare covers PTA of the carotid artery concurrent with the placement of an FDA-approved carotid stent for the following: Patients who are at high risk for carotid endarterectomy (CEA) and who also have symptomatic carotid artery stenosis ≥70%. Coverage is limited to procedures performed using FDA-approved carotid artery stenting systems and FDA-approved or cleared embolic protection devices. If deployment of the embolic protection device is not technically possible, and not performed, then the procedure is not covered by Medicare; Patients who are at high risk for CEA and have symptomatic carotid artery stenosis between 50% and 70%, in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), as a routine cost under the clinical trials policy (Medicare NCD Manual 310.1), or in accordance with the NCD on carotid artery stenting (CAS) post-approval studies (Medicare NCD Manual 20.7B); Patients who are at high risk for CEA and have asymptomatic carotid artery stenosis ≥80%, in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), as a routine cost under the clinical trials policy (Medicare NCD Manual 310.1), or in accordance with the NCD on CAS post- approval studies (Medicare NCD Manual 20.7B). We have decided to make no changes in coverage of patient groups for percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting (Medicare NCD Manual 20.7B3 and B). We have decided to retain our existing coverage policy with a slight revision to the language regarding embolic protection devices.

Decision Memo: To: Administrative File CAG-00085R7 From: Louis B. Jacques, MD Director, Coverage and Analysis Group Tamara Syrek Jensen, JD Deputy Director, Coverage and Analysis Group Marcel E. Salive, MD, MPH Director, Division of Medical and Surgical Services Sarah McClain, MHS Lead Analyst, Division of Medical and Surgical Services Joseph Chin, MD, MS Medical Officer, Division of Medical and Surgical Services Subject: Coverage Decision Memorandum for Percutaneous Transluminal Angioplasty (PTA) of the Carotid Artery Concurrent with Stenting (CAG-00085R7) Date: December 9, 2009 I. Decision The Centers for Medicare and Medicaid Services (CMS) has determined, based on the Food and Drug Administration (FDA) clearance of new embolic protection devices, to revise the national coverage determination (NCD) language regarding embolic protection devices as follows in section B3 and B4 of the NCD: 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 for an FDA-approved indication when furnished in accordance with FDA-approved protocols governing post-approval studies. CMS determines that coverage of PTA of the carotid artery is reasonable and necessary in these circumstances. Medicare covers PTA of the carotid artery concurrent with the placement of an FDA-approved carotid stent for the following: Patients who are at high risk for carotid endarterectomy (CEA) and who also have symptomatic carotid artery stenosis ≥70%. Coverage is limited to procedures performed using FDA-approved carotid artery stenting systems and FDA-approved or cleared embolic protection devices. If deployment of the embolic protection device is not technically possible, and not performed, then the procedure is not covered by Medicare; Patients who are at high risk for CEA and have symptomatic carotid artery stenosis between 50% and 70%, in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), as a routine cost under the clinical trials policy (Medicare NCD Manual 310.1), or in accordance with the NCD on carotid artery stenting (CAS) post-approval studies (Medicare NCD Manual 20.7B); Patients who are at high risk for CEA and have asymptomatic carotid artery stenosis ≥80%, in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), as a routine cost under the clinical trials policy (Medicare NCD Manual 310.1), or in accordance with the NCD on CAS post- approval studies (Medicare NCD Manual 20.7B). We have decided to make no changes in coverage of patient groups for percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting (Medicare NCD Manual 20.7B3 and B). We have decided to retain our existing coverage policy with a slight revision to the language regarding embolic protection devices. II. Background CMS internally generated this reconsideration request for PTA of the carotid artery concurrent with stenting. In the last reconsideration on this topic on October 14, 2008 (CAG-00085R6) CMS stated that "[w]e are aware of other data that has yet to be published and strongly urge that publication at the soonest possible time. We will work with any requestor as soon as that data is published to determine the need for an expedited review and reconsideration." New data have recently been published that examine outcomes in patients for whom coverage is currently limited to participation in clinical trials and post approval studies. In this reconsideration, CMS examines whether coverage should be expanded to beneficiaries who are at high risk for adverse events related to CEA due to anatomic risk factors with asymptomatic carotid artery stenosis of ≥ 80% when CAS procedures are performed outside of clinical trials, FDA approved IDE trials or FDA approved post approval studies. Throughout this document we reference patients who are at high risk due to CEA. When we make this statement we are discussing patients who are at high risk for adverse outcomes if they undergo CEA. These patients may be at high risk for adverse outcomes due to physiologic conditions or anatomic conditions. A list of conditions that cause patients to be at high risk for adverse outcomes if they undergo CEA is provided in the full text of the NCD (Appendix B). Under the current policy patients at high risk for CEA who have symptomatic carotid artery stenosis ≥ 70% are covered for procedures performed using FDA approved CAS systems with embolic protection devices in facilities approved by CMS to perform CAS procedures. In addition, patients at high risk for CEA with symptomatic carotid artery stenosis between 50% and 70% and patients at high risk for CEA with asymptomatic carotid artery stenosis ≥ 80% are covered in accordance with the Category B IDE clinical trials regulation (42, CFR 405.201), as a routine cost under the clinical trials policy (Medicare NCD Manual 310.1), or in accordance with the NCD on CAS post approval studies (Medicare NCD Manual 20.7, B3). III. History of Medicare Coverage Over the past eight years, Medicare has expanded coverage for PTA and stenting of the carotid artery. 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). 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. Medicare’s NCD for PTA concurrent with carotid stenting can be found in NCD Manual 20.7. Medicare’s NCD for PTA concurrent with carotid stenting in FDA approved post approval studies can also be found in NCD Manual 20.7B3. Benefit Category Determination 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. PTA of the carotid artery concurrent with stenting, at a minimum, falls under the benefit categories set forth in section §1861(b) (inpatient hospital services), a part A benefit under §1812(a)(1) and §1861(s)(1) (physician services), a part B benefit. This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service. IV. Timeline of Recent Activities Date Action March 18, 2009 CMS internally generated a reconsideration request to examine newly published evidence. April 17, 2009 Initial 30-day public comment period closed. September 10, 2009 Proposed decision memorandum posted; 30-day comment period begins. V. FDA Status There are currently seven carotid stent systems with Premarket Approval (PMA) approval by the FDA plus five distal filter embolic protection devices (EPDs) and one distal balloon occlusion EPD with FDA 510(k) clearance. Recent FDA 510(k) cleared EPDs include one proximally placed flow reversal EPD and one distally placed filter with focal suction. 1 , 2 VI. General Methodological Principles When making national coverage decisions, under §1862(a)(1)(A), 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 patients. 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. In general, features of clinical studies that improve quality and decrease bias include the selection of a clinically relevant cohort, the consistent use of a single good reference standard, and the blinding of readers of the index test, and reference test results. 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. Public comments that contain personal health information will not be made available to the public. 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. VII. Evidence A. Introduction In this coverage analysis, we considered carotid artery stenting studies and evidence that were published since the last reconsideration in 2008. It incorporates all evidence from prior decision memoranda regarding this issue. A summary of the body of evidence reviewed to date in developing this decision memorandum is available via the final decision memoranda released following the completion of each of the prior national coverage analyses (NCAs) for reconsiderations of the CAS NCD. For carotid artery stenting, we believe that studies should evaluate health outcomes especially in patients who do not have symptoms from carotid artery disease. Health outcomes for carotid artery stenting include death, stroke, myocardial infarction and other adverse events. As noted in the two prior reconsiderations of this topic, we have considered the professional society guidance that the accepted standards for carotid revascularization should apply to CAS if it is to be considered an alternative to CEA. Professional guidelines developed and published by the American Heart Association (AHA) (Sacco, et al., 2006; Goldstein et al., 2006) identify these benchmarks and suggest that CEA is indicated in patients with asymptomatic and symptomatic carotid artery stenosis when surgeons can achieve perioperative morbidity and mortality rates that are < 3% and < 6% respectively. Similar periprocedural rates would be expected to demonstrate that CAS improves health outcomes. Literature Search Because this is a reconsideration, CMS focused on new clinical research studies, technology assessments, guidelines and reviews published since the October 14, 2008 decision memorandum, but also considered literature addressing the patient populations under consideration which was published prior to the 2008 NCD. CMS searched PubMed from January 2008 to October 2009. General keywords included carotid artery stenting, carotid artery angioplasty, risk factors (high risk for surgery and anatomic risk factors). Abstracts without a complete publication were excluded. Using these general parameters, 10 original studies, 2 systematic reviews and 3 sets of evidence based guidelines were found. B. Discussion of evidence reviewed 1. Evidence Questions Our determination of whether to expand coverage of carotid artery stenting for high risk asymptomatic patients under Medicare involves consideration of health outcomes. For this NCD, the questions of interest are: Is the evidence sufficient to conclude that percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting for asymptomatic patients at high risk for adverse events related to CEA with carotid artery stenosis ≥ 80% improves health outcomes compared to carotid endarterectomy or optimal medical therapy outside the clinical trial or post market study setting? Is the evidence sufficient to conclude that percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting for asymptomatic patients with anatomic high risk factors for CEA associated adverse events with carotid artery stenosis ≥ 80% and symptomatic patients with carotid artery stenosis 50-70% improves health outcomes? 2. External Technology Assessments Abbott AL. Medical (Nonsurgical) Intervention Alone Is Now Best for Prevention of Stroke Associated With Asymptomatic Severe Carotid Stenosis Results of a Systematic Review and Analysis. Stroke 2009;40:e573-e583. Abbott reported the results of a systematic review with 3 specific objectives: 1. "To investigate temporal changes in reported stroke (+/-TIA) rate and baseline characteristics among patients with asymptomatic severe carotid stenosis receiving medical intervention alone." 2. "To compare the above stroke (+/-TIA) rates with those of patients who received CEA in major randomized surgical trials." 3. "To compare stroke prevention cost-effectiveness of current medical intervention alone with medical intervention and CEA as employed in major randomized surgical trials." The author included 11 studies (3724 patients with mean age of 66 years). Kaplan–Meier risk estimates were calculated. The author reported: "Significant advances in vascular disease medical intervention since large randomized trials for asymptomatic severe carotid stenosis were conducted (1983–2003) have prompted doubt over current expectations of a surgical benefit. In this systematic review and analysis of published data it was found that rates of ipsilateral and any-territory stroke (+/-TIA), with medical intervention alone, have fallen significantly since the mid-1980s, with recent estimates overlapping those of operated patients in randomized trials. However, current medical intervention alone was estimated at least 3 to 8 times more cost-effective. In conclusion, current vascular disease medical intervention alone is now best for stroke prevention associated with asymptomatic severe carotid stenosis given this new evidence, other cardiovascular benefits, and because high-risk patients who benefit from additional carotid surgery or angioplasty/stenting cannot be identified." While this review focused on CEA, it is relevant to CAS since it is also considered carotid intervention. Ederle J, Featherstone RL, Brown MB. Randomized controlled trials comparing endarterectomy and endovascular treatment for carotid artery stenosis: a Cochrane systematic review. Stroke 2009;40:1373-1380. Ederle and colleagues reported the results of a Cochrane systematic review "to assess the benefits and risks of endovascular treatment compared to surgery." This review provided an update of the Cochrane review done by the same authors in 2007 which reported that the data were "limited and conflicting" and concluded that: "The data support the continuing inclusion of patients within randomized clinical trials between endovascular and surgical treatment for carotid artery stenosis. Randomisation should continue in the ongoing trials and centres not participating in the large multicentre trials should be encouraged to randomise suitable patients locally. This could contribute to any future meta-analysis." For the current review, randomized trials on stenting compared to endarterectomy were selected. Only randomized trials were included so the published registry studies were not. Ten trials (n=3178 patients) were included in the analysis. The primary outcome was stroke or death within 30 days. Intention to treat analysis was used. The Peto fixed effect model was used to calculate odds ratios. The authors found: "Using a fixed-effect model, the odds ratio (OR) for the combined outcome of death or any stroke was significantly in favor of carotid endarterectomy (OR endovascular:surgery 1.40, 95% CI 1.04 to 1.88, P = 0.03)." Identical to the 2007 review, they concluded: "The data are difficult to interpret because the trials are heterogeneous. Five trials were stopped early, perhaps leading to an overestimate of the risks of endovascular treatment. The results do not support a change in clinical practice away from recommending carotid endarterectomy as the treatment of choice for suitable carotid artery stenosis but support continued recruitment in the large ongoing trials." 3. Internal Technology Assessment Chiam PTL, Roubin GS, Panagopoulos G, Iyer SS, Green RM, Brennan C, Vitek JJ. One-year clinical outcomes, midterm survival, and predictors of mortality after carotid stenting in elderly patients. Circulation 2009;119:2343-2348. Chiam and colleagues reported the results of a case series (n=142) of elderly patients who underwent CAS from 2003 to 2007 "to determine survival and predictors of mortality of selected elderly patients after stenting." Inclusion criteria were age ≥ 80 years and symptomatic ≥ 50% diameter stenosis or asymptomatic stenosis ≥ 70%. Patients were non high risk patients. The outcomes included combined death and stroke at 30 days and death at 12 months. Mean age was 83 years. Men comprised 61%. Symptomatic patients comprised 28%. The authors reported: "Among the 153 procedures, 5 events (1 death, 2 major strokes, 2 minor strokes) occurred, resulting in an overall 30-day stroke or death rate of 3.3% (5.1% in the symptomatic group, 2.6% in asymptomatic patients)." At 12 months, 15 (12%) deaths occurred out of 129 patients with at least 1 year of follow-up. The authors concluded: "This study demonstrates that in selected elderly patients, a high proportion (85%) survived 2 years and > 75% survived 3 years after stenting. Carotid stenting may be considered a revascularization option in such patients. Better selection of patients using the predictors of mortality may help to reduce unwarranted procedures and to optimize survival likelihood." Limitations of case series such as selection issues and lack of controls are applicable. Results by symptomatology and anatomic risk factors were not reported. At 12 months, there were 15 deaths and 1 nonfatal stroke for a combined 12.4% (16/129) rate. Although these patients were considered non high risk, the authors noted: "Elderly patients undergoing CS, however, may not represent the "average" elderly patient. No data on survival after CS in elderly patients are available." de Donato G, Setacci C, Deloose K, Peeters P, Cremonesi A, Bosiers M. Long-term results of carotid artery stenting. J Vasc Surg 2008;48:1431-1441. de Donato and colleagues reported the results of an analysis of a registry of 4 European carotid high volume centers (n=3179) "to review long-term results after carotid stent implantation in a large cohort of patients." Patients underwent CAS from 1998 to 2006. Inclusion criteria included "symptomatic lesions ≥ 50%, asymptomatic lesions ≥ 80%, calculated according to the North American Symptomatic Carotid Endarterectomy Trial [NASCET] criteria." Outcomes included death, stroke or other neurological complications. Mean age was about 72 years. Men comprised 67%. Symptomatic patients comprised 41%. The authors reported: "At 5 years freedom from mortality, stroke-related death, ipsilateral fatal/major stroke, and any stroke rate were 82%, 93.5%, 93.3%, and 91.9%, respectively." Rates of all cause mortality and any stroke increased year to year and were similar for symptomatic and asymptomatic patients. The authors concluded: "Our long-term results in a large cohort of patients validated CAS as a durable procedure for stroke prevention. The annual rate of neurological complications after CAS was comparable to that of conventional surgery as demonstrated by large RCTs involving both symptomatic patients (North American Symptomatic Carotid Endarterectomy Trial [NASCET] and European Carotid Surgery Trial [ECST]) and asymptomatic patients (Asymptomatic Carotid Atherosclerosis Study [ACAS] and Asymptomatic Carotid Surgery Trial [ACST])." Limitations of registry studies such as voluntary reporting, selection and lack of controls are applicable. The stroke and death proportions for asymptomatic patients were 3.5%, 8.2%, 15.4%, 20.1% and 26.1% from years 1 to 5 respectively. The authors reported a 1.9% annual rate of stroke. Results by anatomic risk factors were not reported. Surgical risk was not an inclusion criterion. Ederle J, Featherstone RL, Brown MM, CAVATAS collaborators. Long-term outcome of endovascular treatment versus medical care for carotid artery stenosis in patients not suitable for surgery and randomized in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). Cerebrovascular Diseases 2009;23:1-7. Ederle and colleagues reported the results of a randomized controlled trial of patients (n=40) considered unsuitable for carotid endarterectomy in CAVATAS to compare endovascular treatment of carotid stenosis to medical treatment. Patients included in CAVATAS had the "presence of clinically important carotid stenosis" as determined by the individual site investigators. Patients considered unsuitable for CAVATAS had "recent myocardial infarction, poorly controlled, hypertension or diabetes mellitus, renal disease, respiratory failure, inaccessible carotid stenosis, or severe cervical spondylosis" and were randomized (1:1) to carotid intervention (n=20) or medical therapy (n=20) for this subset trial (CAVATAS-MED). Of the 40 patients, 17 patients had surgical contraindications, 14 had medical contraindications, 7 refused surgery and 2 had unrecorded reasons for why they were considered unsuitable for surgery. Primary outcome was death or stroke in the follow-up period. Patients were enrolled from 1992 to 1997. Intention to treat analysis was used. Mean age was about 69 years. Men comprised 78%. Symptomatic patients comprised 63%. Median follow-up was 4.5 years. The authors found 1 death or stroke within 30 days in the endovascular treatment group and 0 death or stroke within 30 days in the medical group. At any time during the follow-up period, there were 9 death or stroke events in both groups. The authors concluded: "We failed to show superiority of endovascular treatment above medical care alone for carotid stenosis in a very small group of patients not suitable for surgical treatment. However, the trial randomized only 40 patients, and was therefore severely underpowered to detect clinically relevant treatment differences. Ongoing trials of carotid stenting will need to demonstrate improved safety and efficacy before endovascular treatment should enter routine practice." In this report, the inclusion criteria were not well defined. Since enrollment started before stents were available, endovascular treatment was variable. The actual number of patients who underwent CAS was not reported. Medical therapy also was not uniformly defined. Results for symptomatic and asymptomatic patients were not reported separately. Gray WA, Chaturvedi S, Verta P, on behalf of the Investigators and the Executive Committees. Thirty-day outcomes for carotid artery stenting in 6320 patients from 2 prospective, multicenter, high-surgical-risk registries. Circ Cardiovasc Intervent 2009;2:159-166. Gray and colleagues reported the results of a combined analysis of "2145 patients from the Emboshield and Xact Post Approval Carotid Stent Trial (EX) and 4175 patients from the Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events (C2)." The objective was to evaluate how outcomes from CAS compared to perioperative morbidity (stroke) and mortality recommendations from the American Heart Association and the American Stroke Association on prevention of stroke in symptomatic and asymptomatic patients (see guidelines in section 5 below). Patients were high-surgical risk individuals who underwent CAS from 2004 to 2006 and had symptomatic (≥ 50% stenosis) or asymptomatic (≥ 80% stenosis) lesions. Of the 6370 patients enrolled in the EX 3 and C2 4 postmarket surveillance studies mandated by the FDA, 6320 patients were included in the analytical dataset. The EX study involved 253 investigators at 128 sites while the C2 study involved 519 investigators at 186 sites. The primary end point of both studies was a composite of death, stroke or myocardial infarction within 30 days of CAS. Mean age was about 73 years. Men comprised about 62% of the subjects. Patient with symptoms of carotid artery stenosis comprised about 12%. The authors reported: "The 30-day primary composite end point (hierarchical) of death, stroke, and MI for EX was 4.1% (95% CI, 3.3% to 5.1%), for C2 was 3.7% (95% CI, 3.1% to 4.3%), and for the combined studies was 3.8% (95% CI, 3.4% to 4.3%). The 30-day combined end point of death and stroke rate for EX was 4.1% (95% CI, 3.3% to 5.0%), 3.4% (95% CI, 2.9% to 4.0%) for C2, and 3.6% (95% CI, 3.2% to 4.1%) for the combined population. For the combined symptomatic population the rate of 30-day death and stroke was 6.4% (95% CI, 4.8% to 8.4%), and for the combined asymptomatic population it was 3.2% (95% CI, 2.8% to 3.7%)." A subgroup analysis of patients with anatomic high surgical risk factors ("history of CEA, radiation, therapy to the neck or radical neck surgery, surgically inaccessible lesion at or above the C2 vertebra or below the clavicle, lesions obstructed by tumors in the neck, spinal immobility/inability to flex neck beyond neutral or kyphotic deformity, the presence of a tracheostomy stoma, and contralateral laryngeal nerve palsy") was also performed. They reported: "The 30-day rate of death and stroke for the 60 symptomatic patients with anatomic factors was 1.7% (95% CI, 0.0% to 8.9%); the single stroke was adjudicated as major. The 30-day rate of death and stroke for the 371 asymptomatic patients with anatomic high-risk features was 2.7% (95% CI, 1.3% to 4.9%), of which 78% were minor." The authors concluded: "Outcomes for carotid artery stenting in nonoctogenarian high-surgical-risk patients have improved since the pivotal Food and Drug Administration approval trials, and have achieved American Heart Association standards in both symptomatic and asymptomatic lesions." They also reported: "This study also carries the limitations of any registry analysis, including limited follow-up duration and the potential for bias in end point detection. Given that any prophylactic procedure requires the patient to survive long enough to reap the benefit of reduced end point events to justify procedural or surgical risk (as per the AHA guidelines document stipulation of an expected 5-year survival), no definitive statements regarding the ultimate benefit of CAS can be made absent long-term follow-up in this population. Last, the separation of patients between high-risk anatomic and physiological features is complex because of the need to rank order the risk factors for categorization (ie, a patient may have both an anatomic and physiological risk), resulting in almost twice the number of octogenarians in the physiological group, and potentially contributing to an increase in outcome events in this cohort." Groeneveld PW, Yang L, Greenhut A, Yang F. Comparative effectiveness of carotid arterial stenting versus endarterectomy. J Vasc Surg 2009;50:1040-8. Groeneveld and colleagues reported the results of a retrospective cohort study to "compare the effectiveness of CAS to CEA in a nonexperimental, nationwide population of Medicare beneficiaries receiving carotid revascularization after the March 2005 Medicare coverage expansion for CAS." Medicare fee for service claims from 2002 to 2006 were examined. ICD-9 codes (00.55, 39.90; 0.061, 0.063) were used to create CAS comparison groups and the CEA group (38.12). Patients who had claims for CAS from October, 2002 to September, 2004 (n=4590; 3% of carotid revascularization patients for the specified time frame) were entered into the "pre-coverage era" group, while patients had claims for CAS from August, 2005 to March, 2006 (n=5354; 11% of carotid revascularization patients for the specified time frame) were entered into the "coverage era" group. Outcomes included mortality, acute myocardial infarction and stroke. Comparisons were performed between areas with high CAS adoption (23% of carotid procedures were CAS) and low adoption (9% were CAS). Propensity scores were used to match patients across eras. Mean age was 76 years. Men comprised 60% of the cohorts. Less than 4 % of patients had a prior diagnosis of stroke or TIA. The authors found no significant difference in 270 day mortality (4.8% coverage era versus 4.6% pre-coverage; P=0.17) but a significant difference in combined outcome of stroke, death, acute myocardial infarction (7.7% coverage era versus 7.3% pre-coverage; P=0.17). They reported: "In localities with higher adoption of carotid stents, there was higher 90-day mortality (adjusted odds ratio [OR] 1.15; P = .16), 90-day combined outcomes (OR = 1.17; P = .03), 270-day mortality (OR = 1.13; P = .07), and 270-day combined outcomes (OR = 1.10; P = .09) in the coverage era." They concluded: "The adoption of carotid stents for treatment of carotid stenosis was associated with increased rates of adverse clinical outcomes after carotid revascularization." As with many studies using administrative claims data, specific clinical information such as symptoms from carotid stenosis or surgical risk factors may not be coded and unavailable in claims data, thus making the matching of cohorts more difficult. Unadjusted differences in the patient cohorts in the high and low adoption areas may potentially influence results. The stroke or death rate was not reported separately. Medical therapy is also difficult to determine in earlier claims data. Kawabata Y, Sakai N, Nagata I, Horikawa F, Miyake H, Ueno Y, Kikuchi H. Clinical predictors of transient ischemic attack, stroke, or death within 30 days of carotid artery stent placement with distal balloon protection. J Vasc Interv Radiol 2009;20:9–16. Kawabata and colleagues reported the results of a case series of 58 patients who underwent carotid artery stenting from 1999 to 2008 "to determine potential clinical risk factors for the development of postprocedural neurologic deficits after carotid artery stent placement." Inclusion criteria included ≥ 50% carotid stenosis if they had recurrent stroke or ≥ 60% carotid asymptomatic stenosis with bilateral carotid lesions or multiple-vessel disease. Primary outcome was combined 30 day major adverse events. Of the 58 patients, 41 were high risk while 17 were low risk. Mean age was 70 years. Men comprised 84%. Symptomatic patients comprised 52%. The authors reported: "Six patients (9.0%) experienced a TIA and one patient (1.5%) had a major stroke (1.5%) within 30 days of the procedure." The 30 day stroke and death rate was 1.5%. They concluded: "Our data suggest that carotid artery stent placement with distal balloon protection can be performed with similar periprocedural complication rates as CEA. CEA should be the first-line treatment in the management of patients older than 75 years of age." Limitations inherent to case studies are applicable. Sample size was small. Low risk patients were included which may lead to reduced 30 day events. Anatomic high risk factors were not evaluated. Massop D, Dave R, Metzger C, Bachinsky W, Solis M, Shah M, et al. Stenting and angioplasty with protection in patients at high-risk for endarterectomy: SAPPHIRE Worldwide Registry first 2,001 patients. Catheterization and Cardiovascular Interventions 2009;73:129–136. Massop and colleagues reported the results of an interim analysis of the SAPPHIRE 5 (Stenting and Angioplasty with Protection of Patients with High Risk for Endarterectomy) Worldwide registry (n=2001) "to evaluate 30-day outcomes after CAS utilizing the CASES training program within a broader number of centers and an increased number of physicians performing the procedure." The SAPPHIRE Worldwide registry (SAPPHIRE WW 6 ) is a post market study being conducted at 350 clinical sites (216 contributed data) in the U.S. and Canada. The primary end point was a composite of death, stroke or myocardial infarction within 30 days of CAS. High surgical risk patients were required to have "either ≥ 50% carotid stenosis (as determined by ultrasound or angiogram) if symptomatic (TIA or stroke within 180 days of the procedure) or ≥ 80% carotid stenosis (as determined by ultrasound or angiogram) if asymptomatic." Of the 2001 patients enrolled from 2006 to 2008, 1620 had complete 30 day follow up data and were included in the analysis. Mean age was about 72 years. Men comprised 62%. Patients with symptoms of carotid stenosis comprised 28%. The authors reported: "The cumulative incidence of MAE at 30 days was 4.4% (95% CI 3.5%, 5.3%), a rate comparable to the MAE rates in previous studies." The rate of death and stroke was 4.0% at 30 days. They also reported: "Asymptomatic patients with anatomic risk factors had a 30-day stroke and death rate of 1.8% while symptomatic patients with anatomic risk factors had a 30-day rate of 4.5% (P=0.0589)." They concluded: "While the number of physicians performing CAS continues to increase, MAE rates seen in this registry (4.4%) are well within an acceptable range, as was first seen in the SAPPHIRE randomized trial (4.8%). A significant decrease in MAE was seen in patients with anatomic risk compared with physiologic risk factors. The SAPPHIRE Worldwide Registry supports the use of CAS as an alternative to CEA in patients who are at high-risk for surgery due to anatomic risk factors." Overall results were not reported separately for asymptomatic and symptomatic patients. The most common anatomic risk factors were previous CEA restenosis and contralateral carotid occlusion. Limitations of registry studies such as voluntary reporting, selection and lack of controls are applicable. Sidawy AN, Zwolak RM, White RA, Siami FS, Schermerhorn ML, Sicard GA, et al. Risk-adjusted 30-day outcomes of carotid stenting and endarterectomy: Results from the SVS Vascular Registry. J Vasc Surg 2009;49:71-79. Sidawy and colleagues reported the results of an analysis of the Society for Vascular Surgery (SVS) Vascular Registry (VR), the "the first operational societal registry of carotid procedures" with 1450 CAS patients, "to report the feasibility of the VR and to provide the baseline demographics and risk-adjusted 30-day outcomes of CAS and CEA." Patients underwent carotid intervention from 2005 to 2007. Specific inclusion and exclusion criteria were not reported. The VR contained data from 287 providers at 56 centers at time of the publication. The primary outcome was combined death, stroke and myocardial infarction at 30 days. Of the CAS patients, mean age was about 71 years. Men comprised 60%. Symptomatic patients comprised 44%. The authors reported: "For CAS, death/stroke/MI at 30 days was 7.13% for symptomatic patients and 4.60% for asymptomatic patients (P=.04)." The combined rate was 5.7% (83/1450) and the death and stroke rate at 30 days was 5.6% (81/1450). The authors concluded: "Following best possible risk adjustment of these unmatched groups, symptomatic and asymptomatic CAS patients had significantly higher 30-day postprocedure incidence of death/stroke/MI when compared with CEA patients. The initial 1.5 years of data collection provide proof of concept that a specialty society based VR can succeed in meeting regulatory and scientific goals. With continued enrollment and follow-up, analysis of SVS-VR will supplement randomized trials by providing real-world comparisons of CAS and CEA with sufficient numbers to serve as an outcome assessment tool of important patient subsets and across the spectrum of peripheral vascular procedures." Results by anatomic risk factors were not reported. Limitations of registry studies such as voluntary reporting, selection and lack of controls are applicable. Simonetti G, Gandini R, Versaci F, Pampana E, Fabiano S, Stefanini M, et al. Carotid artery stenting: findings based on 8 years’ experience. Radiol med 2009;114:95–110. Simonetti and colleagues reported the results of a registry of 1003 patients who underwent CAS from 1999 to 2007 to evaluate 30 day death and stroke. Inclusion criteria were symptomatic stenosis > 50% and asymptomatic lesions with stenosis > 70%, in agreement with the NASCET criteria. Primary outcome was combined 30 day death and stroke. Mean age was 70 years. Men comprised 58%. High risk patients "refused by surgeons" comprised 24%. Symptomatic patients comprised 52%. The authors reported: "The 30-day transient ischaemic attack (TIA)/stroke/death rate was 2.16%: death (0.18%) major stroke (0.45%) and minor stroke/TIA (1.53%). During a follow-up up to 8 years, restenoses occurred in 39 cases (3.57%), of which 28 were post-CAS (2.57%) and 11 post-CAS performed for restenosis after carotid endarterectomy (1%)." Limitations of registry studies such as voluntary reporting, selection and lack of controls are applicable. Low risk patients were included which may lead to reduced adverse event rates. Definitions of low and high risk were not specified. Anatomic high risk factors were not evaluated. Steppacher R, Csikesz N, Eslami M, Arous E, Messina L, Schanzer A. An analysis of carotid artery stenting procedures performed in New York and Florida (2005-2006): Procedure indication, stroke rate, and mortality rate are equivalent for vascular surgeons and nonvascular surgeons. J Vasc Surg 2009;49:1379-86. Steppacher and colleagues reported the results of an analysis of inpatient data from New York and Florida (n=4001) to compare "the indications, in-patient mortality rate, and in-patient stroke rate for patients undergoing CAS, according to operator specialty." Patients were identified by querying inpatient databases from the Healthcare Cost and Utilization Project (HCUP), sponsored by the Agency for Health Care Research and Quality (AHRQ) for International Classification of Disease (ICD)-9-CM codes 00.63 (carotid artery stenting) and 00.61 (carotid artery angioplasty) from 2005-2006. Outcomes included inpatient death and stroke. Symptomatic patients were identified using codes for "transient ischemic attack, amaurosis fugax, or stroke at the time of admission." Mean age was about 71 years. Men comprised 62%. Symptomatic patients comprised 9%. The authors reported overall inhospital mortality and stoke of 2.0%. For symptomatic patients (n=348), the inhospital mortality and stroke was 7.8%. The authors concluded: "Despite a paucity of level 1 evidence for CAS in asymptomatic patients and current Centers for Medicare and Medicaid Services (CMS) policy limiting reimbursement for CAS to only high-risk symptomatic patients, VS (vascular surgeons) and non-VS are treating primarily asymptomatic patients. Perioperative rates of stroke and death are equivalent between VS, IC (interventional cardiologists), and IR (interventional radiologists). Regional variation of operator type is substantial, and despite similar outcomes, < 50% of CAS is performed by VS." Results for asymptomatic patients were not reported. Limitations include those inherent to hospital discharge databases, coding accuracy, difficulties classifying symptom class and lack of data on degree of stenosis. Data were only available for the hospital stays which may not reflect 30 day outcomes in many instances. Usman AA, Tang GL, Eskandari MK. Metaanalysis of procedural stroke and death among octogenarians: carotid stenting versus carotid endarterectomy. J Am Coll Surg 2009;208:1124-1131. Usman and colleagues conducted "a metaanalysis on 41 sets of data from peer-reviewed published articles on CAS versus CEA in octogenarians from 1997 to 2007" and "compared the primary outcomes measures of periprocedural (30-day) myocardial infarction (MI), stroke, and death after CAS or CEA in patients aged 80 years or greater for all studies." Studies were included if 10 or more procedures were performed, 30 day outcomes were reported and 30 day complication rates were available. Eight stenting studies (826 patients) and 33 endarterectomy studies (7017 patients) were evaluated. The authors reported: "In conclusion, octogenarians undergoing CAS had a 3.46-times higher absolute risk of stroke than those undergoing CEA, with no significant difference in mortality and a trend toward a lower rate of MI. Further outcomes research and risk stratification analyses are needed to help guide clinical decision-making. But given that the purpose of carotid intervention is stroke prevention, CAS in octogenarians using current technology should be avoided in favor of CEA or possibly medical management unless a stroke rate of less than 3% can be achieved." Vogel TR, Dombrovskiy VY, Haser PB, Scheirer JC, Graham AM. Outcomes of carotid artery stenting and endarterectomy in the United States. J Vasc Surg 2009;49:325-330. Vogel and colleagues reported the results of an analysis of carotid artery stenting outcomes based on inpatient data from the 2005 Nationwide Inpatient Sample (NIS) "to evaluate national outcomes of CAS and CEA and to compare utilization and outcomes of these procedures in different age groups." The NIS is an "all-payer hospital database developed as part of the Healthcare Cost and Utilization Project (HCUP), sponsored by the Agency for Health Care Research and Quality (AHRQ)." Patients were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code 00.63 for CAS. The analytic database included 6569 patients aged 60 years and older who underwent CAS. Mean age was about 73 years. Men comprised 62%. Symptomatic patients comprised 2.9% (189/6569) and were identified using codes for transient cerebral ischemia, transient paralysis of limb, transient arterial occlusion, transient visual loss, amaurosis fugax and other generalized ischemic cerebrovascular disease. The authors reported: "The overall incidence of stroke was 4.16% after CAS and 2.66% after CEA (P < .0001). CAS was more often utilized in octogenarians than in younger patients (8.55% in 80+ vs 7.92% in 60-69 years; P < .0002). Increased age was not associated with greater stroke rates after CAS or CEA (P=.19 and .06, respectively). Octogenarians, compared to younger patients, had greater cardiac, pulmonary, and renal complications after CEA (3.0% vs 1.9%, 1.9% vs 1.0%, and 1.4% vs 0.54%, respectively; P < .0001)." They found a death and stroke rate of 298/6569 (4.5%) during the inpatient stay for CAS and concluded: "Octogenarians did not have a higher risk of stroke after CAS when compared to younger patients. Stroke was the strongest predictor of hospital mortality. The increased utilization of CAS in the aged, which had significantly higher stroke rates in all age groups studied, may account for the greater hospital mortality seen after CAS in the elderly. Further studies focused on the aged are needed to define the best management strategies in the elderly." Results were not reported by symptomatology although there were very few patients identified as symptomatic patients. Limitations include those inherent to hospital discharge databases, coding accuracy, difficulties classifying symptom class and lack of data on degree of stenosis. Data were only available for the hospital stays which may not reflect 30 day outcomes in many instances. Zarins CK, White RA, Diethrich EB, Shackelton RJ, Siami FS for the CaRESS Steering Committee and CaRESS Investigators. Carotid revascularization using endarterectomy or stenting systems (CaRESS): 4-year outcomes. J Endovasc Ther 2009;16:397–409. Zarins and colleagues reported 4 year outcomes of the Carotid Revascularization using Endarterectomy or Stenting Systems (CaRESS), a "prospective, nonrandomized comparative cohort study of a broad-risk population of symptomatic and asymptomatic patients with carotid stenosis" (initial article in 2003; http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=157 ). Of the total 397 patients, 184 were considered high risk for surgery (107 CEA; 77 CAS patients). Of these, 12 patients had symptomatic stenosis of 50-74% and 133 had asymptomatic stenosis ≥ 75%. For this subset of 145 patients who met CMS’ entry criteria, the authors reported: "There was no difference in death/stroke rates between CEA (3.6%) and CAS (1.7%) at 30 days or at 4 years (CEA 31.5% and CAS 33.5%)." Rates for symptomatic and asymptomatic patients were not presented for this small subgroup. For all 397 patients, 4 year death/stroke rates were 12.4% (5/44) and 25.8% (22/99), respectively. For patients > 80 years of age, 4 year death/stroke rates were 35.4% (13/52) for CEA and 54.1% (13/25) for CAS. The sample sizes for these subgroups were small. 4. MEDCAC No Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) was convened for this issue. 5. Evidence-based guidelines Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushnell CD, Culebras A, DeGraba TJ, Gorelick PB, Guyton JR, Hart RG, Howard G, Kelly-Hayes M, Nixon JVI, Sacco RL. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Stroke 2006;37:1583-1633. This guideline provided "an overview of the evidence on various established and potential stroke risk factors and provides recommendations for the reduction of stroke risk." Specifically for asymptomatic carotid stenosis, the authors stated: "It is recommended that patients with asymptomatic carotid artery stenosis be screened for other treatable causes of stroke and that intensive therapy of all identified stroke risk factors be pursued (Class I, Level of Evidence C). The use of aspirin is recommended unless contraindicated because aspirin was used in all of the cited trials as an antiplatelet drug except in the surgical arm of 1 study, in which there was a higher rate of MI in those who were not given aspirin (Class I, Level of Evidence B). Prophylactic carotid endarterectomy is recommended in highly selected patients with high-grade asymptomatic carotid stenosis performed by surgeons with < 3% morbidity/mortality rates (Class I, Level of Evidence A). Patient selection should be guided by an assessment of comorbid conditions and life expectancy, as well as other individual factors, and be balanced by an understanding of the overall impact of the procedure if all-cause mortality is considered as one of the end points, and it should include a thorough discussion of the risks and benefits of the procedure with an understanding of patient preferences. Carotid angioplasty–stenting might be a reasonable alternative to endarterectomy in asymptomatic patients at high risk for the surgical procedure (Class IIb, Level of Evidence B); however, given the reported periprocedural and overall 1-year event rates, it remains uncertain whether this group of patients should have either procedure." Liapis CD, Bell PRF, Mikhailidis D, Sivenius J, Nicolaides A, Fernandes J, Biasi G, Norgren L, on behalf of the ESVS Guidelines Collaborators. ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques. Eur J Vasc Endovasc Surg 2009;37:S1-S19. Liapis and colleagues reported the European Society for Vascular Surgery evidence based guidelines on carotid stenosis interventions. They used the Agency for Healthcare Research and Quality (AHRQ) grading recommendations 7 and reported: "The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence. Carotid endarterectomy (CEA) is recommended in symptomatic patients with > 50% stenosis if the perioperative stroke/death rate is < 6% [A], preferably within 2 weeks of the patient’s last symptoms [A]. CEA is also recommended in asymptomatic men < 75 years old with 70-99% stenosis if the perioperative stroke/death risk is < 3% [A]. The benefit from CEA in asymptomatic women is significantly less than in men [A]. CEA should therefore be considered only in younger, fit women [A]. Carotid patch angioplasty is preferable to primary closure [A]. Aspirin at a dose of 75-325 mg daily and statins should be given before, during and following CEA. [A] Carotid artery stenting (CAS) should be performed only in high-risk for CEA patients, in high-volume centres with documented low peri-operative stroke and death rates or inside a randomized controlled trial [C]. CAS should be performed under dual antiplatelet treatment with aspirin and clopidogrel [A]. Carotid protection devices are probably of benefit [C]." Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The Am