Technology Assessment Report

Transcription

1 ICSI I NSTITUTE FOR CLINICAL S YSTEMS IMPROVEMENT Report The information contained in this ICSI Report is intended primarily for health professionals and the following expert audiences: physicians, nurses, and other health care professional and provider organizations; health plans, health systems, health care organizations, hospitals and integrated health care delivery systems; medical specialty and professional societies; researchers; federal, state and local government health care policy makers and specialists; and employee benefit managers. This ICSI Report should not be construed as medical advice or medical opinion related to any specific facts or circumstances. If you are not one of the expert audiences listed above you are urged to consult a health care professional regarding your own situation and any specific medical questions you may have. In addition, you should seek assistance from a health care professional in interpreting this ICSI Report and applying it in your individual case. This ICSI Report is designed to assist clinicians by providing a scientific assessment, through review and analysis of medical literature, of the safety and efficacy of medical technologies and is not intended either to replace a clinician s judgment or to suggest that a particular technology is or should be a standard of medical care in any particular case. Standards of medical care are determined on the basis of all the facts and circumstances involved in a particular case and are subject to change as scientific knowledge and technology advance and practice patterns evolve. Copies of this ICSI Report may be distributed by any organization to the organization s employees butmay not be distributed outside of the organization without the prior written consent of the Institute of Clinical Systems Improvement. All other copyright rights in this ICSI Report are reserved by the Institute for Clinical Systems Improvement. The Institute for Clinical Systems Improvement assumes no liability for any adaptations or revisions or modifications made to this ICSI Report.

2 Report Abstract: Carotid, Vertebral and Intracranial Artery Angioplasty and Stenting Prepared under the direction of the Committee by Brent Metfessel, M.D., Staff TA #93 Approved: June 2006 Work Group Leader James Smith, M.D. Internal Medicine HealthPartners Medical Group Work Group Members Bret Haake, M.D. Neurology MeritCare Michael Bacharach, M.D. Cardiology and Vascular Medicine Avera This document is a scientific statement of safety and efficacy only. It is not intended to replace a clinician s judgement or to suggest that a particular technology is or should be a standard of medical care in any particular case. Description of Treatment Stroke is the most common life-threatening neurological disorder and the leading cause of adult long-term disability in North America and is also the third leading cause of death in the United States after heart disease and cancer. Approximately 25% of ischemic stroke events are related to cervical internal carotid occlusive disease with another 8 to 10% of ischemic strokes being due to intracranial arterial occlusive disease. Approximately 700,000 individuals in the United States experience a stroke each year, leading to about $40 billion dollars in direct and indirect costs. Unmodifiable risk factors for stroke include advanced age; male gender; black, Hispanic, or Asian ethnicity; and positive family history. Modifiable risk factors for stroke include hypertension, smoking and environmental tobacco exposure, diabetes and insulin resistance, asymptomatic carotid stenosis, atrial fibrillation and other cardiac diseases, sickle cell disease, and hyperlipidemia. The purpose of the carotid angioplasty and stent (CAS) procedure is to compress the atherosclerotic plaque and expand the lumen in the target carotid artery(s), although no direct plaque excision takes place. The recent introduction of embolic protection devices is purported to trap emboli dislodged during the procedure and thus to decrease the likelihood of procedure-related stroke. Studies have been performed that compare CAS with carotid endarterectomy (CEA), the reference standard, with the purpose of establishing the equivalence (or lack of equivalence) of the two technologies. Vertebral and intracranial stenting has also been studied but to a much more limited extent. Committee Conclusions With regard to carotid, vertebral, and intracranial angioplasty and stenting the ICSI Committee finds the following: 1. Carotid angioplasty and stenting (CAS), especially when using an embolic protection device, is a relatively safe procedure when performed by providers experienced with the technology. 2. A number of short-term studies have shown CAS to be generally equivalent to carotid endarterectomy (the reference standard) in safety and efficacy, especially in populations at increased risk for surgery (i.e., SAPPHIRE trial). However, lack of longer-term follow-up does not permit conclusions regarding CAS in terms of long-term (greater than 1 year) efficacy. Results of ongoing randomized trials may provide further clarity in this area. (Conclusion Grade III) 3. The evidence is scant concerning the efficacy of vertebral and intracranial angioplasty and stenting. Thus, no conclusions can be drawn about the efficacy of these procedures. In addition, vertebral and intracranial artery angioplasty and stenting is technically difficult and carries a high risk of complications, up to 20% in some studies. Please see full report for potential uses, contraindications, efficacy, safety, alternatives, and comparative costs. Copyright 2006 by Institute for Clinical Systems Improvement

3 Report: Carotid, Vertebral and Intracranial Artery Angioplasty and Stenting Prepared under the direction of the Committee by Brent Metfessel, M.D., Staff TA #93 Approved: June 2006 James Smith, M.D., Chair HealthPartners Medical Group Merrill Biel, M.D. ENT Specialty Care Bruce Burnett, M.D. Park Nicollet Health Services Craig Christianson, M.D. UCare Thomas Elliott, M.D. St. Mary s/duluth Clinic Health System Keith Folkert, M.D. BlueCross BlueShield MN John Frederick, M.D. PreferredOne Paul Karazija, M.D. Medica George Klee, M.D., Ph.D. Mayo Clinic Richard Kopher, M.D. HealthPartners Medical Group Thomas Kottke, M.D. HealthPartners Medical Group Kirsten Hall Long, Ph.D. Mayo Clinic Thomas Marr, M.D. HealthPartners Lorre Ochs, M.D. HealthPartners Medical Group Jamie Peters, M.D. Fairview Ridges Arthur Puff, M.D. Metropolitan Health Plan Howard Stang, M.D. HealthPartners Medical Group Paul Swan, M.D. University of Minnesota Physicians Rick Wehseler, M.D. Affiliated Community Medical Centers ICSI technology assessment reports are designed to assist clinicians by providing a scientific assessment, through review and analysis of medical literature, of the safety and efficacy of medical technologies and are not intended to replace a clinician s judgement or to suggest that a particular technology is or should be a standard of medical care in any particular case. Standards of medical care are determined on the basis of all the facts and circumstances involved in a particular case and are subject to changes as scientific knowledge and technology advance and practice patterns evolve. Work Group Members* Work Group Leader: James Smith, M.D. Internal Medicine HealthPartners Medical Group Michael Bacharach, MD Cardiology and Vascular Medicine Avera Bret Haake, MD Neurology MeritCare ICSI Report Process: A topic is selected by the Committee (TAC) based on its relevance to the ICSI Health Care Guidelines and/or interest in the topic by ICSI member or sponsor organizations. A work group of 4 to 6 physicians and other health care professionals is identified. The work group includes a leader who does not perform the procedure/treatment/test that is the focus of the report, a critical reading expert, content expert(s), and, preferably, a primary care physician. Prospective work group members are asked to disclose any potential conflicts of interest relevant to the topic of the report; disclosures are reviewed for unacceptable conflicts. The literature search is completed using MEDLINE; in addition, bibliographies of articles obtained from the literature search are examined to identify articles that may have been missed and work group members are asked to provide key references. The ICSI staff person gets direction on the scope of the report from the work group and prepares a draft report based on the available literature. The evidence is graded according to the system described in the References section of the report. The work group meets to review the draft report and direct the ICSI staff person in revising the report. After approval of the draft report by the work group, the work group leader presents the report to the TAC. Committee members review the report and provide feedback to the work group. The draft report is concurrently distributed to ICSI member organizations and content experts nationwide for their review. All comments received are shared with the work group leader and revisions to the report are made, if necessary. With work group approval of the revisions, the TAC makes the final decision regarding approval of the report for distribution. Reports are approved or not approved based on whether a) the conclusions are supported by the evidence, and b) whether the reviewers' comments were reasonably addressed. Newly approved reports are posted at. Reports are reviewed and revised, if warranted. *See Potential Conflict of Interest Disclosure at the end of the report Copyright 2006 by Institute for Clinical Systems Improvement

4 Introduction Epidemiology of Stroke Stroke is the most common life-threatening neurological disorder and the leading cause of adult longterm disability in North America (Higashada et al., 2005; Blue Cross Blue Shield Asssociation, 2005) and is also the third leading cause of death in the United States after heart disease and cancer (Harrigan et al., 2004; Hanel et al., 2003). Approximately 25% of ischemic stroke events are related to cervical internal carotid occlusive disease (Hanel et al., 2003) with another 8 to 10% of ischemic strokes being due to intracranial arterial occlusive disease (Higashada et al., 2005; Hanel et al., 2005). Approximately 700,000 individuals in the United States experience a stroke each year, leading to about $40 billion dollars in direct and indirect costs (Harrigan et al., 2004). Unmodifiable risk factors for stroke include advanced age; male gender; black, Hispanic, or Asian ethnicity, and positive family history. Modifiable risk factors for stroke include hypertension, smoking and environmental tobacco exposure, diabetes and insulin resistance, asymptomatic carotid stenosis, atrial fibrillation and other cardiac diseases, sickle cell disease, and hyperlipidemia (Goldstein et al., 2001). Description of Treatment Medical treatments for carotid or intracranial arterial stenosis consist of lifestyle changes including smoking cessation, diet and exercise modifications, and medications such as antihypertensives, lipidlowering drugs, and anti-platelet medications (aspirin, ticlopidine, clopidogrel, and dipyridamole) (Hofmann et al., 2002). Antiplatelet medications are especially important for secondary prevention in patients with prior transient ischemic attacks or previous nondisabling stroke (Goldstein et al., 2001; Blue Cross Blue Shield Association, 2005). Surgical treatments can be used in select patients to further reduce the risk of stroke, in particular carotid endarterectomy (CEA) where an arteriotomy is performed with subsequent excision of the carotid atherosclerotic plaque. This procedure is major surgery and usually is performed under general anesthesia, although in select cases regional anesthesia has been used. Recent successes and improvements in CEA technique have made this procedure the reference standard for which other treatments are compared. One of these treatment options includes endovascular procedures such as carotid angioplasty and stenting (CAS), which has been promoted as a less invasive and possibly less risky procedure than CEA, especially in patients with carotid stenoses that are at high risk for surgery. Vertebral and intracranial artery procedures have also been performed in order to reduce stroke and are an area of active investigation. Carotid angioplasty was introduced as a treatment in the early 1980s (Harrigan et al., 2004). However, up until 1995 the procedure was rarely done, with about 523 procedures having been performed (Hanel et al., 2003) by then. Since then improvements in the technique have enabled the procedure to grow in popularity as an alternative to CEA in select patients, especially with the introduction of stenting (Hanel et al., 2003). Subsequently, embolus protection devices were introduced with the purpose of trapping emboli dislodged during the procedure and thus decreasing the likelihood of procedure-related stroke. The purpose of the CAS procedure is to compress the atherosclerotic plaque and expand the lumen in the target carotid artery(s), although no direct plaque excision takes place (Blue Cross Blue Shield Association, 2005). The procedure is normally performed in an operating room with endovascular capabilities. Preoperatively, the patient undergoes diagnostic studies such as duplex ultrasonography with magnetic resonance angiography or plain angiogram of the neck and cerebral circulation. Patients are generally given antiplatelet medication starting about 3 days prior to the procedure. The patient is given conscious sedation throughout the procedure. The circulation is entered percutaneously through the femoral artery (although occasionally the cervical route is taken) and the catheter is threaded up through the common carotid artery and to the area of the lesion. Angiograms are again performed to determine the location of the catheter. The stenosis is predilated with a balloon and an embolic capture device is threaded through the predilated stenosis and placed in the distal extracranial internal carotid artery in order to capture emboli that may be dislodged during the procedure. When such devices are used this procedure is noted as protected CAS or PCAS. The lesion is again dilated in order to place a self-expanding stent, usually composed of nitinol, in the lesion with postdilation using a balloon. The Institute for Clinical Systems Improvement 2

5 distal protection device in the internal carotid artery is then retrieved and additional angiograms are done. The patient is then sent to the recovery room and subsequently to the regular ward. Antiplatelet medications are prescribed for at least one month post-procedure (Eskandari et al., 2005; Groschel et al., 2005b). At this time only one manufacturer s carotid stenting system/cerebral protection device has been approved (ACCULINK and RX ACCULINK stents, Guidant Corp. and ACCUNET and RX ACCUNET cerebral protection filter devices, Guidant Corp.). The devices (combined stent and cerebral protection filter) are indicated for use as a means to reduce stroke risk in patients at high risk for perisurgical complications from CEA and who are either symptomatic with a carotid stenosis of 50% or higher or asymptomatic with a carotid stenosis of 80% or higher (Blue Cross Blue Shield Association, 2005). Literature Search Strategy The following MEDLINE (PubMed) search strategy was used: Carotid stents with restriction to human studies in English, Further studies for analysis were obtained from bibliographies of review articles. Described Uses Described uses for CAS include symptomatic patients with a carotid stenosis of at least 50% of the patent vessel diameter or in asymptomatic individuals with at least 80% stenosis. Patients considered for this procedure are most commonly at high risk for CEA (such as severe CHF or advanced age) or have failed previous CEA procedures. Efficacy of Treatment Evidence Summary The evidence for the efficacy of CAS, vertebral and intracranial artery stenting is generally of fair to poor quality. One randomized controlled study of CAS versus CEA, the SAPPHIRE trial (Yadav et al., 2004) used a relatively large sample size of patients at high surgical risk and was of strong design. However, the short follow-up time (1 year) made drawing conclusions concerning the long-term safety and efficacy of CAS difficult. Studies that followed patients longer than 1 year tended to be nonrandomized trials or case series. Those performing meta-analyses on CAS consistently stated that the studies were highly heterogenous. In addition, patients were often not stratified based on symptomatic versus asymptomatic stenoses (the SAPPHIRE trial was a notable exception), high or low surgical risk, or degree of carotid stenosis. Embolic devices are recent innovations and thus they were included during later stages of the investigations. Consequently, many studies had a mixture of procedures using emboli-protection devices and procedures using no protective devices, which may make conclusions difficult to draw. Outcomes were often measured using composite variables, making it difficult to unravel the individual components. Confidence intervals tended to be wide and many of the designs were case series, a weaker design compared to randomized controlled trials. There is also a lack of trials comparing CAS with optimal medical care to optimal medical care alone. Large trials are now under way and firmer conclusions concerning the safety and efficacy of CAS may be drawn after the studies are published. The evidence is scant pertaining to vertebral and intracranial artery angioplasty. The studies that are in the peer-reviewed literature had very small sample sizes (typically less than 20 patients) and there were clear difficulties with complications in those trials. As a result, the evidence at this time does not support the use of carotid, vertebral, or intracranial angioplasty or stenting as a way to relieve stenosis, especially due the lack of data on long-term efficacy and safety from the treatments. Institute for Clinical Systems Improvement 3

6 Carotid Artery Angioplasty and Stenting Bergeron et al. (2005) reported on a single-center case series involving 193 patients (221 CAS procedures). Patients undergoing CAS had high lesions, postradiotherapy or postendarterectomy stenoses, or were at high risk for CEA surgery (severe cardiac dysfunction, unstable angina, requirement for combined coronary revascularization and CAS, severe pulmonary dysfunction, contralateral carotid occlusion, and tandem intracranial lesions). Average patient age was 71.9 years with 77.7% being male. The average follow-up time was 2.7 years (range 1 month to 9.3 years) and no patients were lost to follow-up. The first 112 patients underwent the procedure between 1991 and 1998 and did not have an embolic protection device inserted. Patients treated after that time did have the device inserted during the procedure. Early results showed that the technical success rate was 96.3% with 10 procedural TIAs (4.5%) and 3 procedural strokes (1.55%). No periprocedural deaths were noted. During the 30-day period postprocedure, the all-stroke and death rate combined was 3.6% which included two fatal intracerebral hemorrhages. Another patient died 9 months later of an intracerebral hemorrhage. Two stent occlusions occurred. Predictors of neurologic complications using the Fisher test showed that male gender, lesions involving the carotid bifurcation, femoral route of catheter introduction rather than the cervical route, use of cerebral protection devices, and the use of self-expanding rather than balloon-expandable stents were found to increase the risk of neurologic complications. During the follow-up period, 15% of patients died from non-neurologic causes. Two patients died from contralateral stroke and one from intracerebral hemorrhage. Life-table analysis at 10 years showed a 98% freedom from fatal stroke. Overall freedom from neurologic events at 10 years was 90% and overall freedom from stroke was 96%. The in-stent restenosis rate was 3.2% at 2 years, with an overall late restenosis rate of 6.8%. The report concludes that the late outcome of CAS appears competitive with surgery (CEA), although randomized trials are needed to confirm the findings. Bibl et al. (2005) conducted a case series investigation of internal carotid stent placement without emboli protection. Patients were divided into three groups; symptomatic patients with at least 60% stenosis (n=134), asymptomatic patients with at least 80% stenosis (n=143), and asymptomatic progressive stenosis with at least 60% lumen occlusion (n=25). Mean patient age was 73.1 years with 68.2% being male. Patients were followed for a mean of 27.1 months. Within 30 days after stenting, stroke and death from stroke occurred in 4.7% of symptomatic and 3.0% of asymptomatic patients. During the follow-up period, stroke occurred in 2.3% of symptomatic and 1.2% of asymptomatic patients. Other than patients who died, 7.1% were lost to follow-up. No fatal stroke was reported during the follow-up period. Slightly over 10% of patients had late restenosis of at least 50% occlusion. The authors state that the results are comparable to literature reports of outcomes from CEA. Brooks et al. (2001) performed a single-center randomized controlled trial to compare outcomes from CAS (n=53) to results from CEA (n=51). Mean age was about 68 years. The most common presentation was TIA. All patients received treatment within 6 weeks of the presenting symptom(s). Patients were followed for 2 years. After CAS, stenosis decreased to an average of 5%. No patient sustained a stroke after either CAS or CEA, although one patient died of myocardial infarction immediately after performance of CEA. As for CAS, the most common side effects were transient bradycardia and hypotension due to carotid body stimulation. Patient perception of pain and discomfort were similar for CEA and CAS as was the average length of hospital stay (1.8 days for CAS versus 2.7 days for CEA for procedures without complications, difference NS). Complications after CAS were more likely to prolong hospitalization compared with complications after CEA (with a mean of 5.6 days versus 3.8 days respectively). Return to normal activities within one week occurred in 80% of CAS patients as compared to 67% of CEA patients. The patency of the ipsilateral carotid artery remained intact during the follow-up period (24 months) for both CEA and CAS. The authors concluded that CAS is equivalent to CEA in terms of reduction of carotid stenosis without resulting in a higher rate of major complications such as death or stroke. However, given the fact that the trial was limited to a single center and the team that performed the procedures was highly experienced, the investigators stated that they could not yet advocate that CAS should replace CEA as the primary procedure for revascularization in patients with symptomatic carotid stenosis. Burton and Lindsay (2005) performed a meta-analysis of perioperative (30-day) outcomes of CAS with cerebral protection devices (PCAS). Outcomes of interest included any stroke and any stroke or death. Institute for Clinical Systems Improvement 4

7 Twenty-six studies met inclusion criteria and resulted in a pooled sample size of 2,992 patients treated with PCAS. The pooled perioperative stroke rate (any type) and death rate was 2.4%. The minor stroke rate was 1.1% and major stroke rate was 0.6%, with the perioperative mortality rate being 0.9%. Overall, complication rates appeared low, and this result compares favorably with historical results from CEA. Limitations of the study include heterogeneity between studies including proportions of symptomatic versus asymptomatic patients, types of devices used, and differences in amount of carotid occlusion and assessment of risk factors. Case series studies were also included, weakening the strength of the evidence. Further results from ongoing randomized controlled trials are needed to determine the efficacy of PCAS in treating carotid stenoses, especially in patients at high risk for invasive surgery. The Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS) Steering Committee (2005) authored a prospective, multicenter, nonrandomized phase I trial in order to evaluate whether PCAS is comparable to CEA in cases of symptomatic and asymptomatic carotid stenosis. The CEA group enrolled 254 patients (mean age 71.4 years, 63% men) and the PCAS group enrolled 143 patients (mean age 71.2 years, 60% men). Of the 397 patients, 32% were symptomatic, 68% were asymptomatic, 84% were at high risk for surgery (80 years of age or older, NYHA class III/IV CHF, COPD, contralateral stenosis of over 50%, prior CEA or CAS, or prior CABG), and 16% were at low risk. No differences were found between the groups in terms of surgical risk, symptoms, or patient characteristics. The choice of treatment was based solely on patient and physician preference, which the authors felt better reflected actual clinical practice. As for primary end points, Kaplan-Meier analysis did not show any significant differences between PCAS and CEA in terms of combined stroke and death rates at 30-days postprocedure (3.6% for CEA versus 2.1% for PCAS) or at 1-year (13.6% for CEA versus 10.0% for PCAS). There also were no significant differences for the combined end point of death, stroke, or myocardial infarction at 30 days (4.4% for CEA versus 2.1% for PCAS) or at 1-year follow-up (14.3% for CEA versus 10.9% for PCAS). As for secondary end points, there were no significant differences at 1-year between groups for residual stenoses (0% for CEA versus 0.9% for PCAS), restenosis (3.6% for CEA versus 6.3% for PCAS), repeat angiography (2.1% for CEA versus 3.6% for PCAS), carotid revascularization (1.0% for CEA versus 1.8% for PCAS) or change in quality of life score (-1.56 points for CEA versus points for PCAS). Multivariate analysis did not find significant baseline predictors of outcome with the exception of age (odds ratio, 1.056, p = ) and previous carotid interventional treatment (odds ratio, 2.786, p = ) for the 1-year combined end point of death, stroke, or myocardial infarction. The authors state that the 30-day and 1-year risk of death, stroke, or myocardial infarction with PCAS is approximately equivalent to CEA in the treatment of symptomatic and asymptomatic patients with carotid stenosis. Although this is a non-randomized study, the investigators suggested that patient selection for this study more closely resembled patient selection in actual clinical practice. The Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) was conducted to ascertain the risks and benefits of carotid angioplasty as compared to CEA (CAVATAS Investigators, 2001). In this multicenter randomized controlled trial, 504 patients were assigned to either endovascular treatment (n=251) or CEA (n=253). Mean age was 67 years and about 70% of patients were male. For endovascular patients, stents were used in 26% and balloon angioplasty was used alone in 74%. Intention to treat analysis was used. Mean follow-up period was slightly less than 2 years, with only seven patients being followed up for less than 6 months. Treatment crossover rate was 1.6%. Thirty-day major outcome event rates showed no significant differences between groups, including disabling stroke or death (6.4% for endovascular treatment versus 5.9% for CEA), and stroke lasting more than 7 days or death (10.0% for endovascular treatment versus 9.9% for CEA). Cranial neuropathy was noted in 8.7% of surgery patients but in none of the endovascular patients (p < ). Major hematomas of the neck or groin occurred less often with endovascular treatment than with CEA (1.2% for endovascular treatment versus 6.7% for CEA, p < ). At 1-year follow-up, severe (70% to 99%) stenosis of the ipsilateral carotid artery was more common after endovascular treatment (14%) than after CEA (4%) (p < 0.001). Using survival analysis, no significant difference was found between groups in the rate of ipsilateral stroke up to 3 years post-randomization (adjusted hazard ratio, 1.04, p = 0.9). The investigators conclude that endovascular treatment had similar efficacy and risks in terms of stroke prevention as carotid surgery, although the confidence intervals were wide. Endovascular treatments may have an advantage in terms of fewer minor complications such as hematomas and cranial neuropathy. McCabe et al. (2005) evaluated restenosis rates in the CAVATAS trial. Doppler ultrasound was used to evaluate extent of restenosis at approximately 1 month and 1 year post-procedure (the mean follow-up Institute for Clinical Systems Improvement 5

8 time after randomization was 358 days). The authors found that more patients had at least 70% ipsilateral carotid stenosis at 1 year in the carotid angioplasty group than in the endarterectomy group (18.5% versus 5.2% respectively, p = ). The results were significantly better in stented arteries as compared to arteries undergoing angioplasty without stenting at the 1-month follow-up point (p < 0.001) but the comparative gains from stenting were not statistically significant after 1 year. The authors point out that poor early results (i.e., inferior techniques of balloon angioplasty) may have accounted for about one-third of severe stenosis cases at 1 year follow-up in the endovascular group. Qureshi et al. (2005) conducted a meta-analysis comparing carotid angioplasty with and without stent to carotid endarterectomy for treatment of carotid stenosis. A random effects model was selected for use since significant heterogeneity among studies was noted. Five randomized controlled trials were found that totaled 1154 patients, with 577 randomized to CEA and 577 to CAS. The combined end point of stroke or death 1-month post-procedure was the same for CAS as compared to CEA (relative risk [RR], 1.3; 95% CI, 0.6 to 2.8; p = 0.5). In addition, the 1-month stroke rate (RR, 1.3; 95% CI, 0.4 to 3.6; p = 0.7), disabling stroke rate (RR, 0.9; 95% CI, 0.2 to 3.5; p = 0.9), and 1-year rates of ipsilateral stroke (RR, 0.8; 95% CI, 0.5 to 1.2; p = 0.2) were also similar between groups but the information on the 1-year ipsilateral stroke rate is less rigorous compared to the 1-month rates. However, 1-month myocardial infarction rate (RR, 0.3; 95% CI, 0.1 to 0.9) and injury to cranial nerves (RR, 0.05; 95% CI, 0.01 to 0.3) were significantly lower for CAS as compared to CEA. The authors state that further information will need to await large randomized controlled trials now underway such as the Carotid Revascularization Endarterectomy versus Stent Trial that may show evidence for support of one method over another for use in clinical practice. Yadav et al. (2004) conducted the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) that randomized 334 patients at increased surgical risk into a CAS group (with cerebral protection devices, n=167) and a CEA group (n=167). Mean age was about 72.6 years with 67% male sex. Eligibility criteria included a symptomatic carotid stenosis of at least 50% of the luminal diameter or an asymptomatic carotid stenosis of at least 80%. To qualify for increased surgical risk, at least one of the following criteria must be met: clinically significant heart disease, severe pulmonary disease, contralateral carotid artery occlusion, contralateral laryngeal nerve palsy, previous radical neck surgery or radiation therapy to the neck, recurrent stenosis after CEA, or age > 80 years. The trial evaluated the Cordis PRECISE Nitinol Stent and the ANGIOGUARD Embolic Capture Guide-wire System. In the periprocedural period (up to 30 days) the incidence of stroke, MI, or death was 4.8% for CAS patients and 9.8% among CEA patients in the intention-to-treat analysis (p = 0.09). The primary end point of cumulative incidence of a major cardiovascular event at 1-year post-procedure (including the combined end points of death, stroke, or MI within 30 days after the procedure or death or ipsilateral stroke between 31 days and 1 year after the procedure) occurred in 12.2% of cases randomized to CAS and in 20.1% of cases randomized to CEA (absolute difference, 7.9 percentage points, 95% CI, -16.4% to 0.7%; p = for noninferiority; p = for superiority). When stratifying patients for symptomatology, the symptomatic patients did not show a significant difference between the groups in terms of the primary end point (16.8% for CAS versus 16.5% for CEA). For asymptomatic patients, the CAS group showed a lower frequency of primary end point occurrences (9.9%) as compared to 21.5% for CEA patients (p = 0.02). The mean hospital stay was 1.84 days among CAS patients and 2.85 days for CEA patients (p = 0.002). At 1 year follow-up, fewer patients in the CAS group needed revascularization as compared to CEA patients (cumulative incidence 0.6% versus 4.3%, p = 0.04). Thus, CAS using emboli-protection devices does not appear to be inferior to CEA in the prevention of stroke, death, or MI among increased surgical risk patients, although the follow-up period was short. The authors state that these findings are not generalizable to patients at lower risk for surgery. Chan et al. (2005) studied methods for prevention of distal embolization during carotid artery angioplasty. Between 1998 and 2002, 305 consecutive patients who were treated by percutaneous carotid intervention in a single center (Cleveland Clinic) were followed prospectively for evidence of embolization. During the enrollment and treatment of the patients, embolic protection devices entered the clinical arena, and their safety and efficacy in terms of embolic protection were compared to platelet glycoprotein IIb/IIIa inhibitors (GPIs) such as abciximab. One hundred ninety-nine patients received adjunctive GPIs and 106 received embolic protection devices (85% filter design and 15% balloon occlusion). The combined endpoint of neurologic death, nonfatal stroke, and major bleeding including intracranial hemorrhage was significantly lower among the patients treated with embolic protection Institute for Clinical Systems Improvement 6

9 devices as compared to the GPI group (0% and 5.1% respectively, p = 0.02). The study suggests that embolic protection devices may be more efficacious in protection from procedure-related neurologic events than medications alone, although this study was of a weaker design (case series). Coward et al. (2004) performed a systematic review of randomized trials pertaining to the comparison of CEA to endovascular treatment or endovascular treatment with optimal medical therapy to optimal medical therapy alone. Patients with either symptomatic or asymptomatic carotid stenoses were considered. Two completed randomized controlled trials comparing carotid endovascular treatment to CEA were found, including a total of 608 patients. In addition, two more trials with a total of 242 patients were stopped early and another trial with 307 patients had completed its initial follow-up of 30 days. Four studies are ongoing, including the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), Endarterectomy versus Angioplasty trial (EVA-3S), the International Carotid Stenting Study (ICSS), and Stent-Protected Percutaneous Angioplasty of the Carotid versus Endarterectomy (SPACE). Meta-analysis of included data from the 5 studies noted no significant difference between the odds of death or any stroke within 30-days after the procedure for angioplasty versus CEA (odds ratio [OR] 1.26, 95% CI 0.82 to 1.94). There were also no significant differences detected in terms of the odds of death or disabling stroke 30-days post-procedure (OR 1.22, 95% CI 0.61 to 2.41). At 1-year follow-up, no significant differences were found between the 2 groups in terms of prevention of stroke or death (OR 1.36, 95% CI 0.87 to 2.13). However, endovascular treatment led to a highly significant decrease in risk of cranial neuropathy as compared to surgery (OR 0.12, CI 0.06 to 0.25). There was no significant decrease in risk of death, any stroke, or MI during the 1-year follow-up period (OR 0.99, 95% CI 0.66 to 1.48). The investigators concluded that although similar risks of early stroke or death and long-term benefit exists between surgery and endovascular treatment, there was enough heterogeneity in the data, including two trials stopped early due to safety questions (which may overestimate risks of endovascular treatment, especially since these were relatively early trials from the late 1990s and early 2000s). Other uncertainties included the lack of data on the short or long-term restenosis potential subsequent to the endovascular procedure. Overall, it was believed that the meta-analysis does not support a significant change in terms of continuing to use CEA as the treatment of choice for carotid artery stenosis in patients suitable for surgery. The results of ongoing randomized trials are needed before firmer conclusions can be drawn regarding the role of endovascular treatment for carotid artery stenosis. A later systematic review concerning the comparison of endovascular techniques to carotid surgery for carotid stenosis was conducted by the same authors (Coward et al., 2005b). Five trials involving 1269 patients were reviewed. Analysis of data within 30 days of the procedure showed no significant differences between treatment groups in the odds of treatment-related stroke or death (OR for endovascular procedures 1.33, 95% CI 0.86 to 2.04), death or disabling stroke (OR 1.22, 95% CI 0.61 to 2.41), or stroke, myocardial infarction, or death (OR 1.04, 95% CI 0.69 to 1.57). Within a 1-year follow-up period after randomization, no significant differences were noted between groups in the rate of any stroke or death (OR 1.01, 95% CI 0.71 to 1.44). However, as found in the previous meta-analysis, the risk of cranial nerve injury was significantly decreased (OR 0.13, 95% CI 0.06 to 0.25). The authors state that the wide confidence intervals and substantial heterogeneity between the studies make drawing firm conclusions on the comparison of endovascular treatments and CEA difficult. A systematic review on carotid restenoses (defined as a narrowing of at least 50%) after CAS was performed by Groschel et al. (2005a). Thirty-four studies with a total of 4185 patients were included. A total of 371 patients or arteries were lost to follow-up, resulting in a total number of 3814 arteries analyzed. The median follow-up period was 13 months. Restenosis was measured from duplex ultrasound or angiography. The restenosis criteria were highly variable, with restenosis thresholds varying from 50% to 80% stenosis. Concerning the studies with a restenosis threshold between 50% and 70%, the 1 and 2-year cumulative restenosis rates were about 6% and 7.5% respectively. Concerning the studies with a restenosis threshold between 70% and 80%, the 1 and 2-year restenosis rates were both about 4%. The cumulative restenosis rate after 1 year was about 6% and after 2 years was 7.5%. About 46% of all restenoses occurred within the first 6 months post-procedure, with 25% occurring at 6 to 12 months and 29% occurring after 1 year follow-up. Data were not sufficient to determine risk of ipsilateral stroke due to restenosis compared to patients without restenosis. The authors suggest that although the early restenosis rates after CAS appear to compare with those of surgery, CAS restenosis rates may be greater than previously suggested by observational studies. The trials reviewed tended to have small Institute for Clinical Systems Improvement 7

10 sample sizes and short follow-up periods and thus results regarding restenosis after CAS need to be supported with findings from larger trials. Kastrup et al. (2005) evaluated clinical predictors of significant sequelae within 30 days of CAS. The clinical characteristics of 299 patients (mean age 69 years, 217 men) were analyzed in a prospective fashion. Patients with long or multiple coronary stenoses, severe peripheral vascular disease which would prevent femoral artery access, or a tortuous coronary artery configuration were excluded from the study. During the CAS procedure, 117 patients did not receive cerebral protection devices during the procedure while 182 patients received filter-type embolic protection. Asymptomatic patients made up 43% of the population with symptomatic patients covering the rest (57%). The overall 30-day TIA rate was 3.7% along with a 5.3% minor stroke rate. The major stroke rate was 0.7% and the death rate was 0.7%. Initial presentation with a hemispherical TIA or minor stroke was associated with a significantly increase risk rate (TIA, minor stroke, major stroke, and death) (OR 5.69; 95% CI, 2.03 to 19.57; p < 0.001), the complication rates between patients presenting with a retinal TIA and asymptomatic patients was similar (OR, 1.42; 95% CI 0.13 to 9.09; p = 0.6). Multivariate regression analysis identified advanced age (OR, 1.06; 95% CI, 1 to 1.11; p < 0.05), stroke (OR, 8; 95% CI 2.6 to 24.4; p < 0.01), and hemispheric TIA (OR, 4.7; 95% CI, 1.6 to 13.3) as presenting symptoms that are independent clinical predictors of the 30- day composite outcome measure of any TIA, stroke, or death. No significant differences were evident between patients with and without cerebral protection devices in terms of the 30-day composite outcome. The authors recommended that when comparing CAS to CEA, patients should be stratified based on presenting clinical characteristics. Kastrup et al. (2003) conducted a systematic review concerning the efficacy of cerebral protection devices for preventing periprocedural (within 30 days post-procedure) adverse outcomes. In 2350 patients (2537 CAS procedures) the procedure was performed without protection devices, whereas in 839 patients (896 CAS procedures) the procedure was performed with protection devices. Both groups were similar in indications for CAS, age and gender distribution, and cerebrovascular risk factors. Although in many studies the results were not separated on symptomatology (symptomatic versus asymptomatic patient status), the combined stroke and death rate during the periprocedural period was 1.8% in patients given cerebral protection devices compared to 5.5% in patients treated without such devices (p < 0.001). Most of this effect was due to a reduction in minor stroke frequency (3.7% without protection as compared to 0.5% with protection; p < 0.001) along with a reduction in major strokes (1.1% without protection as compared to 0.3% with cerebral protection; p < 0.05). Death rates were similar between the groups, amounting to about 0.8% in each group during the 30-day period. The authors stated that the use of cerebral protection devices seems to decrease the rate of thromboembolic complications (major and minor stroke). The evidence compiled in the review often consisted of case series and uncontrolled studies that were widely heterogenous, making the overall conclusion less strong given the weaker study designs reviewed. Vertebral and Intracranial Artery Angioplasty and Stenting Coward et al. (2005a) conducted a systematic review concerning endovascular treatment of vertebral artery stenosis. Surgery for vertebral artery stenosis is technically difficult and highly risky, and thus percutaneous transluminal angioplasty and stenting of the vertebral artery has been considered as an alternative to surgery in these cases. Literature search found 1 randomized trial with 16 patients (8 patients assigned to endovascular treatment and 8 to medical treatment as the sole modality). Although 2 patients had a posterior TIA during the angioplasty procedure, there were no strokes or death from any cause in either group up to 30-days post-procedure (endovascular group) or post-randomization (medical group). Patients were followed for a mean period of 4.5 years in the angioplasty group and 4.9 years in the group receiving medical treatment alone. Mean vertebral artery stenosis at follow-up was 47%. During the follow-up period there were no vertebrobasilar strokes in either group. The authors stated that there is insufficient evidence to assess the safety and efficacy of percutaneous transluminal angioplasty with and without stenting as a treatment for vertebral artery stenosis. There is a need for larger, well-designed randomized trials in this area. Kim et al. (2004) studied stent-assisted angioplasty in 14 patients with symptomatic middle cerebral artery (MCA) stenosis (greater than 60%). Symptoms included TIA and stroke. The procedure was successfully performed in 8 patients but unsuccessfully in 2 patients due to tortuous internal carotid Institute for Clinical Systems Improvement 8

11 arteries. Four patients had complications, including two patients with arterial rupture which led to one death. The other two patients had thrombotic occlusion and distal thrombosis. Patients were angiographically followed for 7 to 24 months, and mean clinical follow-up was 11 months (3 to 27 months). On a modified Rankin scale, 4 out of 5 TIA patients and 5 out of 6 stroke patients were evaluated as functionally improved or clinically stable. Although the procedure may be successful in a subset of patients, the risk is still high. Further research in the form of randomized controlled trials is still needed prior to drawing conclusions regarding MCA angioplasty and stenting. Yu et al. (2005) enrolled 18 patients with symptomatic basilar artery stenosis for angioplasty and stenting in an uncontrolled study. There were 3 major periprocedural complications including right sided hemiparesis and dysarthria in one patient, oculomotor nerve palsy and depressed consciousness secondary to intraventricular and subarachnoid hemorrhages in another patient, and profuse bleeding from the femoral artery, the oropharynx, and the urethra. No fatalities related to the procedure were reported. However, 15 patients (83.3%) of had excellent long-term functional outcome scores (MRS score less than or equal to 1). Thus, although the outcome of most patients was good in this study, the major complication rate was high. The authors suggest that due to the poor prognosis of basilar artery stenosis, randomized trials in this area are warranted despite the high risk of the stenting procedure. The Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA, 2004) investigators undertook a nonrandomized multicenter, prospective feasibility study using the NEUROLINK System for treatment of vertebral or intracranial artery stenosis. The study enrolled 61 patients 18 to 80 years old (mean age 63.6 years, 82% male) and had symptoms that could be attributed to a single stenosis of 50% or greater. Forty-three intracranial arteries and 18 extracranial vertebral arteries received angioplasty and stenting. The stenting procedure was performed successfully in 95% of cases. The follow-up period was up to 1 year. At 6 months follow-up, 32.4% of intracranial and 42.9% of extracranial vertebral arteries had recurrences of greater than 50% stenosis, with 7 recurrent stenoses being symptomatic. As for strokes, 7.3% of patients had strokes later than 30 days (4 patients, including a patient not stented). Overall, strokes occurred in 6.6% of patients within 30 days and in 7.3% of patients between 30 days and 1 year. Most restenosis occurrences were asymptomatic. No deaths were reported within 30 days, although one stroke-related fatality occurred within the 1 year follow-up period. The authors state that the NEUROLINK system is relatively safe and feasible for treating atherosclerotic lesions of the intracranial arteries and extracranial vertebral arteries, but further studies are needed in larger populations prior to drawing conclusions pertaining to the technology. Safety of Treatment Morbidity Rate The technical success rate for CAS is high and is on the order of 97% to 99% for experienced operators. Complications such as emboli, carotid artery spasm, thrombosis, dissection, and hyperperfusion syndrome may occur, but are in general uncommon (van den Berg, 2004). Other periprocedural (within 30 days after procedure performance) complications include TIA (3.7%), minor stroke (5.3%), and major stroke (0.7%). This relatively low rate of complications assumes that the operators are experienced in the CAS procedure (Kastrup et al., 2005). The use of embolic capture devices downstream from the location of the procedure may protect against stroke in patients where emboli become dislodged during the procedure (Kastrup et al., 2003). The risk of vertebral and intracranial stenting is high, including major strokes and arterial rupture. Frequencies of major periprocedural complications range from about 7% to 20% (SSYLVIA, 2004; Yu et al., 2005). The studies generally had small sample sizes which prevents the drawing of rigorous conclusions for vertebral and intracranial stenting. Institute for Clinical Systems Improvement 9

12 Mortality Rate The periprocedural mortality rate for experienced CAS operators is low, generally on the order of 0.7% to 0.8% (Kastrup et al., 2003; Kastrup et al., 2005). Sample sizes were too small to draw firm conclusions regarding vertebral and intracranial stenting mortality, but may be approximately 1% to 3% (SSYLVIA, 2004; Kim et al., 2004) Training and Experience Required to Perform the Treatment Carotid stenting is a technically complex procedure, where minor embolic events can lead to major complications, and thus has a learning curve. One study showed a stroke rate of 7.1% for operators performing fewer than 15 procedures (Schneider and Rapp, 2005). Vertebral and intracranial artery stenting is even more technically demanding than carotid stenting and has a high complication rate. The safety of this procedure or the learning curve required to achieve competence is not known. Conditions and Setting of Treatment Carotid, vertebral, and intracranial stenting is generally performed in a hospital setting. After the procedure, the patient is sent to the recovery room for a few hours and then is transferred to the general ward. Length of stay is usually 1 3 days. If these procedures are performed, a multidisciplinary approach that involves primary care, vascular surgery, cardiology, interventional radiology, and neurology providers is essential for optimal care of the patient undergoing carotid, vertebral, or intracranial procedures. Contraindications and Comorbidities that Increase the Risk Associated with the Treatment Contraindications and comorbidities for endovascular procedures are spelled out in the exclusions for the SAPPHIRE trial and include ischemic stroke within the previous 48 hours, intraluminal thrombus, total occlusion of relevant vessel, vascular disease that does not allow for endovascular techniques, intracranial aneurysm, the need for more than 2 stents, bleeding disorder, life expectancy less than 1 year, and ostial lesions of common carotid or brachiocephalic artery (Yadav et al., 2004) Potential for Inappropriate Use of the Technology These procedures do have the potential for overutilization and many health plans have developed medical policies around the use of such procedures. Alternative Treatments Surgical and endovascular treatments, particularly for those with asymptomatic carotid stenoses, are a second-line treatment to be used when medical treatments fail. First-line medical treatments for asymptomatic and selected symptomatic carotid stenosis (e.g., secondary prevention in patients with a history of TIA) consist of smoking cessation, diet and exercise modifications, and medications including antihypertensives, lipid-lowering drugs, and anti-platelet medications (aspirin, ticlopidine, clopidogrel, and dipyridamole) (Hofmann et al., 2002). Other than medical treatments (described above) CEA has been shown to be effective for appropriately selected patients and is considered the reference standard for evaluations of CAS. To perform the CEA procedure, the patient is given general anesthesia although more recently regional anesthesia is sometimes provided. An incision is made to expose the target artery and the artery is clamped. An incision is made into the artery. After entering the artery, the surgeon removes the plaque in the inner lining of the artery. The operator then stitches the artery shut and the clamp is removed. The procedure lasts approximately 2 hours (Society for Vascular Surgery, 2004). Institute for Clinical Systems Improvement 10

13 Economic Implications of Treatment Kilaru et al. (2003) compared CAS to CEA in terms of immediate and longer term cost-effectiveness. In order to evaluate cost-effectiveness, a Markov decision analysis model was developed. CEA data were obtained from a retrospective analysis of 447 consecutive patients treated at a single center, whereas CAS data were obtained from literature review. Both procedural costs and long-term cost of morbidities and illnesses were taken into consideration. Major stroke cost was set at $52,019 during the first year and $27,336 per subsequent year. The cost of minor stroke was set at a flat rate of $9419. A hypothetical cohort of 70-year old patients was used to ascertain long-term survival rates in terms of quality-adjusted life years (QALYs) and lifetime costs for CEA and CAS patients. The immediate costs of the procedures were $7871 for CEA and $10,133 for CAS. Assumptions included a major and minor stroke rate of 0.9% (CEA) and 5% (CAS), and a 30-day mortality rate of 0% (CEA) and 1.2% (CAS). Base case analysis showed that CEA was cost saving using this model, with a lifetime savings of $7017 per patient and an increase in QALYs saved of 0.16 (based on total QALYs of 8.20 for CAS and 8.36 for CEA). On sensitivity analysis, major stroke and death rates appeared to be the variables most associated with differences in cost-effectiveness between CAS and CEA. Procedural costs and minor stroke rates were less important in the analysis. CAS was cost-effective only if major stroke and death rates were equivalent to CEA. Committee Conclusions With regard to carotid, vertebral, and intracranial angioplasty and stenting, the ICSI Technology Assessment Committee finds the following: 1. Carotid angioplasty and stenting (CAS), especially when using an embolic protection device, is a relatively safe procedure when performed by providers experienced with the technology. 2. A number of short-term studies have shown CAS to be generally equivalent to carotid endarterectomy (the reference standard) in safety and efficacy, especially in populations at increased risk for surgery (i.e., SAPPHIRE trial). However, lack of longer-term follow-up does not permit conclusions regarding CAS in terms of long-term (greater than 1 year) efficacy. Results of ongoing randomized trials may provide further clarity in this area. (Conclusion Grade III) 3. The evidence is scant concerning the efficacy of vertebral and intracranial angioplasty and stenting. Thus, no conclusions can be drawn about the efficacy of these procedures. In addition, vertebral and intracranial artery angioplasty and stenting is technically difficult and carries a high risk of complications, up to 20% in some studies. Potential Conflict of Interest Disclosure In the interest of full disclosure, ICSI has adopted the policy of revealing relationships work group members have with companies that sell products or services that are relevant to this technology assessment report topic. The reader should not assume that these financial interests will have an adverse impact on the content of the technology assessment report, but they are noted here to fully inform readers. Readers of the technology assessment report may assume that only work group members listed below have potential conflicts of interest to disclose. ICSI's conflict of interest policy and procedures are available for review on ICSI's Web site at. Institute for Clinical Systems Improvement 11

14 Evidence Grading System Evidence is classed and graded as described below. I. CLASSES OF RESEARCH REPORTS II. A. Primary Reports of New Data Collection: Class A: Class B: Class C: Class D: Randomized, controlled trial Cohort study Non-randomized trial with concurrent or historical controls Case-control study Study of sensitivity and specificity of a diagnostic test Population-based descriptive study Cross-sectional study Case series Case report B. Reports that Synthesize or Reflect upon Collections of Primary Reports: Class M: Class R: Class X: Meta-analysis Systematic review Decision analysis Cost-effectiveness analysis Consensus statement Consensus report Narrative review Medical opinion CONCLUSION GRADES Key conclusions (as determined by the work group) are supported by a conclusion grading worksheet that summarizes the important studies pertaining to the conclusion. Individual studies are classed according to the system defined in Section I, above, and are assigned a designator of +, -, or ø to reflect the study quality. Conclusion grades are determined by the work group based on the following definitions: Grade I: The evidence consists of results from studies of strong design for answering the question addressed. The results are both clinically important and consistent with minor exceptions at most. The results are free of any significant doubts about generalizability, bias, and flaws in research design. Studies with negative results have sufficiently large samples to have adequate statistical power. Grade II: The evidence consists of results from studies of strong design for answering the question addressed, but there is some uncertainty attached to the conclusion because of inconsistencies among the results from the studies or because of minor doubts about generalizability, bias, research design flaws, or adequacy of sample size. Alternatively, the evidence consists solely of results from weaker designs for the question addressed, but the results have been confirmed in separate studies and are consistent with minor exceptions at most. Grade III: The evidence consists of results from studies of strong design for answering the question addressed, but there is substantial uncertainty attached to the conclusion because of inconsistencies among the results from different studies or because of serious doubts about generalizability, bias, research design flaws, or adequacy of sample size. Alternatively, the evidence consists solely of results from a limited number of studies of weak design for answering the question addressed. Grade Not Assignable: the conclusion. There is no evidence available that directly supports or refutes The symbols +,, ø, and N/A found on the conclusion grading worksheets are used to designate the quality of the primary research reports and systematic reviews: Institute for Clinical Systems Improvement 12

15 References + indicates that the report or review has clearly addressed issues of inclusion/exclusion, bias, generalizability, and data collection and analysis; indicates that these issues have not been adequately addressed; ø indicates that the report or review is neither exceptionally strong or exceptionally weak; N/A indicates that the report is not a primary reference or a systematic review and therefore the quality has not been assessed. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet 2001;357: Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS) phase I clinical trial: 1- year results. J Vasc Surg 2005;42: Angioplasty and stenting of the cervical carotid artery with distal embolic protection of the cerebral circulation. Blue Cross Blue Shield Association TEC Assessment, Volume 19(15), Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA): study results. Stroke 2004;35: Bergeron P, Roux M, Khanoyan P, Douillez V, Bras J, Gay J. Long-term results of carotid stenting are competitive with surgery. J Vasc Surg 2005;41: ; discussion Bibl D, Lampl C, Biberhofer I, et al. Internal carotid artery stent placement without emboli protection: results and long-term outcome. Neurology 2005;65: Brooks WH, McClure RR, Jones MR, Coleman TC, Breathitt L. Carotid angioplasty and stenting versus carotid endarterectomy: randomized trial in a community hospital. J Am Coll Cardiol 2001;38: Burton KR, Lindsay TF. Assessment of short-term outcomes for protected carotid angioplasty with stents using recent evidence. J Vasc Surg 2005;42: Chan AW, Yadav JS, Bhatt DL, et al. Comparison of the safety and efficacy of emboli prevention devices versus platelet glycoprotein IIb/IIIa inhibition during carotid stenting. Am J Cardiol 2005;95: Coward LJ, Featherstone RL, Brown MM. Percutaneous transluminal angioplasty and stenting for carotid artery stenosis. Cochrane Database Syst Rev:CD000515, Coward LJ, Featherstone RL, Brown MM. Percutaneous transluminal angioplasty and stenting for vertebral artery stenosis. Cochrane Database Syst Rev:CD000516, 2005(a). Coward LJ, Featherstone RL, Brown MM. Safety and efficacy of endovascular treatment of carotid artery stenosis compared with carotid endarterectomy: a Cochrane systematic review of the randomized evidence. Stroke 2005(b);36: Eskandari MK, Longo GM, Matsumura JS, et al. Carotid stenting done exclusively by vascular surgeons: first 175 cases. Ann Surg 2005;242: ; discussion Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke 2001;32: Groschel K, Riecker A, Schulz JB, Ernemann U, Kastrup A. Systematic review of early recurrent stenosis after carotid angioplasty and stenting. Stroke 2005a;36: Institute for Clinical Systems Improvement 13

16 Groschel K, Ernemann U, Riecker A, Schmidt F, Terborg C, Kastrup A. Incidence and risk factors for medical complications after carotid artery stenting. J Vasc Surg 2005b;42: ; discussion Hanel RA, Xavier AR, Kirmani JF, Yahia AM, Qureshi AI. Management of carotid artery stenosis: comparing endarterectomy and stenting. Curr Cardiol Rep 2003;5: Hanel RA, Levy EI, Guterman LR, Hopkins LN. Cervical carotid revascularization: the role of angioplasty with stenting. Neurosurg Clin N Am 2005;16: , viii. Harrigan MR, Howington JU, Hanel RA, Guterman LR, Hopkins LN. Patient selection for revascularization in cervical carotid artery disease: angioplasty and stenting vs. endarterectomy. Am Heart Hosp J 2004;2:8-15. Higashida RT. Intracranial stenting: which patients and when? Cleve Clin J Med 2004;71 Suppl 1:S Higashida RT, Meyers PM, Connors JJ, et al. Intracranial angioplasty & stenting for cerebral atherosclerosis: a position statement of the American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, and the American Society of Neuroradiology. J Vasc Interv Radiol 2005;16: Hofmann R, Kerschner K, Steinwender C, Kypta A, Bibl D, Leisch F. Abciximab bolus injection does not reduce cerebral ischemic complications of elective carotid artery stenting: a randomized study. Stroke 2002;33: Kastrup A, Groschel K, Krapf H, Brehm BR, Dichgans J, Schulz JB. Early outcome of carotid angioplasty and stenting with and without cerebral protection devices: a systematic review of the literature. Stroke 2003;34: Kastrup A, Groschel K, Schulz JB, Nagele T, Ernemann U. Clinical predictors of transient ischemic attack, stroke, or death within 30 days of carotid angioplasty and stenting. Stroke 2005;36: Kilaru S, Korn P, Kasirajan K, et al. Is carotid angioplasty and stenting more cost effective than carotid endarterectomy? J Vasc Surg 2003;37: Kim JK, Ahn JY, Lee BH, et al. Elective stenting for symptomatic middle cerebral artery stenosis presenting as transient ischaemic deficits or stroke attacks: short term arteriographical and clinical outcome. J Neurol Neurosurg Psychiatry 2004;75: McCabe DJ, Pereira AC, Clifton A, Bland JM, Brown MM. Restenosis after carotid angioplasty, stenting, or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). Stroke 2005;36: Qureshi AI, Kirmani JF, Divani AA, Hobson RW, 2nd. Carotid angioplasty with or without stent placement versus carotid endarterectomy for treatment of carotid stenosis: a meta-analysis. Neurosurgery 2005;56: ; discussion Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in highrisk patients. N Engl J Med 2004;351: Yu W, Smith WS, Singh V, et al. Long-term outcome of endovascular stenting for symptomatic basilar artery stenosis. Neurology 2005;64: Institute for Clinical Systems Improvement 14

17 Conclusion Grading Worksheet See next page Institute for Clinical Systems Improvement 15

18 Institute for Clinical Systems Improvement 16