Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial, we found no significant difference between the stenting group and the endarterectomy group with respect to the primary composite end point of stroke, myocardial infarction, or death during the periprocedural period or any subsequent ipsilateral stroke during 4 years of follow-up. We now extend the results to 10 years. METHODS: Among patients with carotid-artery stenosis who had been randomly assigned to stenting or endarterectomy, we evaluated outcomes every 6 months for up to 10 years at 117 centers. In addition to assessing the primary composite end point, we assessed the primary end point for the long-term extension study, which was ipsilateral stroke after the periprocedural period. RESULTS: Among 2502 patients, there was no significant difference in the rate of the primary composite end point between the stenting group (11.8%; 95% confidence interval [CI], 9.1 to 14.8) and the endarterectomy group (9.9%; 95% CI, 7.9 to 12.2) over 10 years of follow-up (hazard ratio, 1.10; 95% CI, 0.83 to 1.44). With respect to the primary long-term end point, postprocedural ipsilateral stroke over the 10-year follow-up occurred in 6.9% (95% CI, 4.4 to 9.7) of the patients in the stenting group and in 5.6% (95% CI, 3.7 to 7.6) of those in the endarterectomy group; the rates did not differ significantly between the groups (hazard ratio, 0.99; 95% CI, 0.64 to 1.52). No significant between-group differences with respect to either end point were detected when symptomatic patients and asymptomatic patients were analyzed separately. CONCLUSIONS: Over 10 years of follow-up, we did not find a significant difference between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. The rate of postprocedural ipsilateral stroke also did not differ between groups. (Funded by the National Institutes of Health and Abbott Vascular Solutions; CREST ClinicalTrials.gov number, NCT00004732.).

Influence of multiple stents on periprocedural stroke after carotid artery stenting in the Carotid Revascularization Endarterectomy versus Stent Trial (CREST).

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stent Trial (CREST), carotid artery atherosclerotic lesion length and nature of the lesions were important factors that predicted the observed difference in stroke rates between carotid endarterectomy and carotid artery stenting (CAS). Additional patient-related factors influencing CAS outcomes in CREST included age and symptomatic status. The importance of the operator's proficiency and its influence on periprocedural complications have not been well defined. We evaluated data from CREST to determine the impact of use of multiple stents, which we speculate may be related to technical proficiency. METHODS: CREST includes CAS performed for symptomatic ≥50% carotid stenosis and asymptomatic ≥70% stenosis. Both symptomatic and asymptomatic patients were enrolled in the trial and in the lead-in registry. Data from patients enrolled in the CREST registry and randomized trial from 2000 to 2008 were reviewed for patient- and lesion-related characteristics along with number of stents deployed. The occurrence of 30-day stroke and demographic and clinical features were recorded. Odds ratios for 30-day stroke associated with the use of multiple stents were calculated in univariate analysis and on multivariable analysis after adjustment for demographics (age, sex, symptomatic status), lesion characteristics (length, ulceration, eccentric, percentage stenosis), and risk factors (diabetes, hypertension, dyslipidemia, and smoking). RESULTS: The registry (n = 1531) and trial (n = 1121) enrolled 2652 patients undergoing CAS. The mean age was 69 years; 36% were women, and 38% were symptomatic. The mean diameter stenosis was 78%, and the mean lesion length was 18 mm (±standard deviation, 8 mm). Risk factors included hypertension (85%), diabetes (32%), dyslipidemia (84%), and smoking (23%). All patients received Acculink stents (Abbott Vascular, Abbott Park, Ill) that were 20, 30, or 40 mm in length (straight or tapered) and Accunet (Abbot Vascular) embolic protection when possible. Most patients received one stent (n = 2545), whereas 98 patients received two stents and 9 patients received three stents (P < .001) to treat the lesion. Patients receiving more than one stent were older (P = .01) but did not differ in other demographic or risk factors. Strokes occurred in 118 (4.5%) of all CAS procedures, in 102 (4%) with the use of one stent, and in 16 (15%) with the use of two or three stents. After adjustment for demographics, lesion characteristics, and risk factors, the use of more than one stent resulted in 2.90 odds (95% confidence interval, 1.49-5.64) for a stroke. CONCLUSIONS: Although we know that lesion characteristics (length, ulceration) play an important role in CAS outcomes, in this early experience with carotid stenting, a significant and independent relationship existed between the number of stents used and procedural risk of CAS. We postulate that this was an indicator of the operator's inexperience with the procedure.

Stenting versus endarterectomy for treatment of carotid-artery stenosis.

BACKGROUND: Carotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke. METHODS: We randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization. RESULTS: For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85). CONCLUSIONS: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)

The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase.

The success of carotid artery stenting in preventing stroke requires a low risk of periprocedural stroke and death. A comprehensive training and credentialing process was prerequisite to the randomized Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) to assemble a competent team of interventionalists with low periprocedural event rates. Interventionalists submitted cases to a multidisciplinary Interventional Management Committee. This committee evaluated 427 applicants. Of these, 238 (56%) were selected to participate in the training program and the lead-in phase, 73 (17%) who had clinical registry experience and satisfactory results with the devices used in CREST were exempt from training and were approved for the randomized phase, and 116 (27%) did not qualify for training. At 30 days in the lead-in study, stroke, myocardial infarction, or death occurred in 6.1% of symptomatic subjects and 4.8% of asymptomatic subjects. Stroke or death occurred in 5.8% of symptomatic subjects and 3.8% of asymptomatic subjects. Outcomes were better for younger subjects and varied by operator training. Based on experience, training, and lead-in results, the Interventional Management Committee selected 224 interventionalists to participate in the randomized phase of CREST. We believe that the credentialing and training of interventionalists participating in CREST have been the most rigorous reported to date for any randomized trial evaluating endovascular treatments. The study identified competent operators, which ensured that the randomized trial results fairly contrasted outcomes between endarterectomy and stenting.

Does sex matter? Thirty-day stroke and death rates after carotid artery stenting in women versus men: results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) lead-in phase.

BACKGROUND AND PURPOSE: Several carotid endarterectomy randomized, controlled trials and series have reported higher perioperative stroke and death rates for women compared with men. The potential for this same relationship with carotid artery stenting was examined in the lead-in phase of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). METHODS: CREST compares efficacy of carotid endarterectomy and carotid artery stenting in preventing stroke, myocardial infarction, and death in the periprocedural period and ipsilateral stroke over the follow-up period. CREST included a "lead-in" phase of symptomatic (>or=50% stenosis) and asymptomatic (>or=70% stenosis) patients. Patients were examined by a neurologist preprocedure, at 24 hours, and at 30 days. Review of stroke and death was by an independent events committee. The association of sex with periprocedural stroke and death was examined in 1564 patients undergoing carotid artery stenting (26.5% symptomatic). RESULTS: Women comprised 37% of the lead-in cohort and did not differ from men by age, symptomatic status, or characteristics of the internal carotid artery. The 30-day stroke and death rate for women was 4.5% (26 of 579; 95% CI, 3.0% to 6.5%) compared with 4.2% (41 of 985; 95% CI, 3.0% to 5.6%) for men. The difference in stroke and death rate was not significant nor were there any significant differences by sex after adjustment for age, arterial characteristics, or cardiovascular risk factors. CONCLUSIONS: These results do not provide evidence that women have a higher carotid artery stenting stroke and death rate compared with men. The potential differential periprocedural risk by sex will be prospectively addressed in the randomized phase of CREST.

Outcome of carotid artery stenting for primary versus restenotic lesions.

Carotid artery stenting (CAS) for restenosis (RS) after carotid endarterectomy (CEA) is presumed to have fewer complications than CAS for primary atherosclerotic (PA) lesions. It has been proposed that interventionalists may limit themselves to CAS for RS initially, while they gain additional experience during their learning curve. However, there are few studies objectively comparing the outcomes of the two groups of patients to substantiate this assumption. We analyzed prospectively collected data on CAS performed at our institution from 1996 to April 2006. Complication rates were compared between CAS performed for RS versus PA lesions. Specific end points studied included in-hospital and 30-day stroke and death rates. The incidence of transient ischemic attack (TIA) was also recorded. Patient demographic features (gender, age, hypertension, diabetes mellitus, coronary artery disease, smoking, hypercholesterolemia, and presence of preoperative neurological symptoms) were recorded. A neurologist examined all patients before and after CAS. Patients with previous CAS with in-stent RS and tandem common carotid artery-internal carotid artery or arch ostial stenoses were excluded from this analysis. CAS procedures (n = 217) performed on 210 patients fulfilled inclusion criteria for this study. Indications for CAS included RS (n = 118, 54%) and PA (n = 99, 46%). The two groups were well matched for all demographic features except hypercholesterolemia, which was more common in the PA group. Thirty-day stroke and stroke + death rates for the entire series were 2.8% and 4.1%, respectively. Within this cohort, 30-day stroke and stroke + death rates were not significantly different between the RS (2.5% and 5.1%) and PA (3.0% and 3.0%) groups. Within the RS group, these outcomes were also similar when patients treated for late recurrence (>24 months after CEA, n = 49) were compared to those treated for early recurrence (< or = 24 months after CEA, n = 67). Only when stroke and TIA were combined was a difference observed between the late recurrence (10.0%) and the early recurrence (1.5%) groups (p = 0.049). Contrary to general opinion, 30-day stroke and stroke + mortality rates from CAS for RS versus PA were not significantly different. Lower neurological event rates were only seen in CAS for early RS compared with late RS after endarterectomy when TIAs were included as an end point in the analysis. CAS for RS must therefore not be considered a low-risk procedure. Technical proficiency for CAS must be equivalent regardless of the etiology of the stenosis. These observations also underscore the need for appropriate patient selection and close follow-up of all patients undergoing CAS.

Gaps in public knowledge of peripheral arterial disease: the first national PAD public awareness survey.

BACKGROUND: Lower-extremity peripheral arterial disease (PAD) is associated with decreased functional status, diminished quality of life, amputation, myocardial infarction, stroke, and death. Nevertheless, public knowledge of PAD as a morbid and mortal disease has not been previously assessed. METHODS AND RESULTS: We performed a cross-sectional, population-based telephone survey of a nationally representative sample of 2501 adults > or = 50 years of age, with oversampling of blacks and Hispanics. The survey instrument measured the demographic, risk factor, and cardiovascular disease characteristics of the study population; prevalent leg symptoms; PAD awareness relative to atherosclerosis risk factors and other cardiovascular and noncardiovascular diseases; perceived causes of PAD; and perceived systemic and limb consequences of PAD. Respondents were 67.2+/-12.6 years of age with a high prevalence of risk factors but only a modest burden of known coronary or cerebrovascular disease. Twenty-six percent of respondents expressed familiarity with PAD, a rate significantly lower than that for any other cardiovascular disease or atherosclerosis risk factor. Within the "PAD-aware" cohort, knowledge was poor. Half of these individuals were not aware that diabetes and smoking increase the risk for PAD; 1 in 4 knew that PAD is associated with increased risk of heart attack and stroke; and only 14% were aware that PAD could lead to amputation. All knowledge domains were lower in individuals with lower income and education levels. CONCLUSIONS: The public is poorly informed about PAD, with major knowledge gaps regarding the definition of PAD, risk factors that lead to PAD, and associated limb symptoms and amputation risk. The public is not aware that PAD imposes a high short-term risk of heart attack, stroke, and death. For the national cardiovascular disease burden to be reduced, public PAD knowledge could be improved by national PAD public education programs designed to reduce critical knowledge gaps.

Endarterectomy vs stenting for carotid artery stenosis: a systematic review and meta-analysis.

OBJECTIVES: The relative efficacy and safety of endarterectomy and stenting in patients with carotid stenosis remain unclear. In this review we synthesize the available evidence derived from randomized controlled trials (RCTs) that compared the two procedures in terms of the risks of death, stroke (disabling and nondisabling), and nonfatal myocardial infarction. METHODS: We searched for RCTs in MEDLINE, EMBASE, Current Contents, and Cochrane CENTRAL; expert files, and bibliographies of included articles. Two reviewers, working independently, determined trial eligibility and extracted descriptive, methodologic, and outcome data from each eligible RCT. Random-effects meta-analysis was used to assess relative and absolute risks and the I(2) statistic was used to assess heterogeneity of treatment effect among trials. RESULTS: Ten RCTs with 3182 participants proved eligible. At 30 days and compared with endarterectomy, carotid stenting was associated with a nonsignificant reduction in the risk of death (relative risk [RR], 0.61; 95% confidence interval [CI], 0.27-1.37; I(2) = 0%), a nonsignificant reduction in the risk of nonfatal myocardial infarction (RR, 0.43; 95% CI 0.17-1.11; I(2) = 0%), and a nonsignificant increase in the risk of any stroke (RR, 1.29; 95% CI, 0.73-2.26; I(2) = 40%) and major/disabling stroke (RR, 1.06; 95% CI, 0.32-3.52; I(2) = 45%). If one considers the two procedures equivalent if the absolute difference in events is <2%, these results provide moderate-quality evidence for equivalence with respect to death (risk difference [RD] -0.40, 95% CI -1.02 to 0.40) and nonfatal myocardial infarction (RD, -0.70; 95% CI -1.90 to 0.50), but because of much wider CI, only low-quality evidence of equivalence in stroke (RD, 1.00; 95% CI, -1.00 to 3.10). CONCLUSION: In RCTs, carotid stenting and carotid endarterectomy seem equivalent in terms of death and nonfatal myocardial infarction. Although the impact on stroke remains unestablished, results are consistent with a clinically important increase in stroke risk with stenting, an intervention that aims at reducing the risk of stroke.

Management of atherosclerotic carotid artery disease: clinical practice guidelines of the Society for Vascular Surgery.

The Society for Vascular Surgery (SVS) appointed a committee of experts to formulate evidence-based clinical guidelines for the management of carotid stenosis. In formulating clinical practice recommendations, the committee used systematic reviews to summarize the best available evidence and the GRADE scheme to grade the strength of recommendations (GRADE 1 for strong recommendations; GRADE 2 for weak recommendations) and rate the quality of evidence (high, moderate, low, and very low quality). In symptomatic and asymptomatic patients with low-grade carotid stenosis (<50% in symptomatic and <60% in asymptomatic patients), we recommend optimal medical therapy rather than revascularization (GRADE 1 recommendation, high quality evidence). In symptomatic patients with moderate to severe carotid stenosis (more than 50%), we recommend carotid endarterectomy plus optimal medical therapy (GRADE 1 recommendation, high quality evidence). In symptomatic patients with moderate to severe carotid stenosis (>/=50%) and high perioperative risk, we suggest carotid artery stenting as a potential alternative to carotid endarterectomy (GRADE 2 recommendation, low quality evidence). In asymptomatic patients with moderate to severe carotid stenosis (>/=60%), we recommend carotid endarterectomy plus medical management as long as the perioperative risk is low (GRADE 1 recommendation, high quality evidence). We recommend against carotid artery stenting for asymptomatic patients with moderate to severe (>/=60%) carotid artery stenosis (GRADE 1 recommendation, low quality evidence). A possible exception includes patients with >/=80% carotid artery stenosis and high anatomic risk for carotid endarterectomy.

Diagnosis and invasive management of carotid atherosclerotic stenosis.

Carotid atherosclerotic stenosis is a known risk factor for ischemic stroke. Methods for detecting stenosis and revascularization abound. The objective of this review was to summarize the evidence for diagnosing carotid artery stenosis and treating symptomatic or asymptomatic stenosis with endarterectomy or stenting. An Ovid MEDLINE search identified relevant original research published between 1990 and 2006. With acceptable surgical risk and patient life expectancy, carotid endarterectomy is clearly indicated for symptomatic stenosis of more than 70%. Carotid endarterectomy is also recommended for symptomatic stenosis of more than 50%, but the health impact is less compelling. The US Food and Drug Administration has approved several stents for a subset of patients with carotid stenosis. Randomized comparisons of endarterectomy vs stenting have been performed in average- and high-risk patients with asymptomatic and symptomatic carotid artery stenosis with mixed results.

Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary practice guidelines committee of the American Society of Neuroimaging; cosponsored by the Society of Vascular and Interventional Neurology.

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the screening for asymptomatic carotid artery stenosis in the general population and selected subsets of patients. Recommendations are included for high-risk persons in the general population; patients undergoing open heart surgery including coronary artery bypass surgery; patients with peripheral vascular diseases, abdominal aortic aneurysms, and renal artery stenosis; patients after radiotherapy for head and neck malignancies; patients following carotid endarterectomy, or carotid artery stent placement; patients with retinal ischemic syndromes; patients with syncope, dizziness, vertigo or tinnitus; and patients with a family history of vascular diseases and hyperhomocysteinemia. The recommendations are based on prevalence of disease, anticipated benefit, and concurrent guidelines from other professional organizations in selected populations.

Randomized clinical trials: impact on clinical practice for symptomatic and asymptomatic extracranial carotid occlusive disease.

Carotid artery stenting (CAS) has emerged as a useful and potentially less invasive alternative to carotid endarterectomy (CEA) for the treatment of extracranial carotid stenoses. In this regard, it has been suggested that specific patient subgroups who may benefit from CAS including those with significant medical comorbidities, recurrent stenosis, anatomically inaccessible lesions, and a hostile neck. However, the purpose of this report is to evaluate whether or not CAS should replace CEA in the treatment of symptomatic and asymptomatic disease in better risk patients, also. This report contains results from recently published randomized clinical trials.

Carotid stenting: should it replace endarterectomy in higher-risk patients?

Carotid artery stenting (CAS) has emerged as a useful and potentially less-invasive alternative to carotid endarterectomy (CEA) for treatment of extracranial carotid stenoses. It has been suggested that specific patient subgroups, including those with significant medical comorbidities, recurrent stenosis, anatomically inaccessible lesions, and a hostile neck, might benefit from CAS. The purpose of this report is to evaluate whether or not CAS should replace CEA in the treatment of the high-risk patient. Results from a recently published randomized clinical trial and several individual center and multicenter case analyses will be used in this review.

Organizing the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): National Institutes of Health, Health Care Financing Administration, and industry funding.

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is a prospective, randomized, multicenter clinical trial of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) as prevention for stroke in patients with symptomatic stenosis greater than or equal to 50%. CREST is sponsored by the US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH), with additional support by a device manufacturer, and will provide data to the US Food and Drug Administration (FDA) for evaluation of a stent device. Because of budget constraints for CREST, Health Care Financing Administration (HCFA) reimbursement for hospital costs incurred by CREST patients will be essential. The involvement of academic scientists, industry, and three separate government agencies (NIH, FDA, HCFA) has presented many challenges in conducting the trial. A review of the pathways followed to meet these challenges may be helpful to others seeking to facilitate sharing of the costs and burdens of conducting innovative clinical research.

Carotid artery stenting.

Efficacy for carotid artery stenting (CAS) has not been confirmed by randomized clinical trial methodology in conventional risk patients. Although carotid endarterectomy (CEA) is considered the preferred method for carotid revascularization in the management of patients with symptomatic and asymptomatic extracranial carotid occlusive disease, comparisons between CAS and CEA are now underway. In North America, the CREST (Carotid Revascularization Endarterectomy versus Stent Trial) protocol is now completing its lead-in or credentialing phase as randomization of cases is initiated. In Europe, the CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study) and Stent Protected Angioplasty versus Carotid Endarterectomy trials are recruiting symptomatic patients for randomization between CEA and CAS. It is anticipated that these trials will publish definitive results within the next 1 to 3 years, and help guide the referral of patients for CAS and CEA in the future.

Rationale and status of randomized controlled clinical trials in carotid artery stenting.

Efficacy for carotid artery stenting (CAS) has not been confirmed by randomized clinical trial methodology. Although carotid endarterectomy (CEA) is considered the preferred method for carotid revascularization in the management of patients with asymptomatic and symptomatic extracranial carotid occlusive disease, comparisons between CAS and CEA are now underway. In North America, the CREST (Carotid Revascularization Endarterectomy versus Stent Trial) protocol is now completing credentialing cases as randomization of cases is initiated. In Europe, the CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study) and SPACE (Stent Protected Angioplasty versus Carotid Endarterectomy) trials are recruiting symptomatic patients for randomization between CEA and CAS. It is anticipated that these trials will publish definitive results within the next 1-3 years and help guide the referral of patients for CAS and CEA in the future.