Carotid Revascularization Endarterectomy Research Articles

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Treatment of Symptomatic Carotid Stenosis: Carotid Stent Placement Versus Endarterectomy

The mainstay of treatment options for symptomatic carotid stenosis is focused around medical management, carotid endarterectomy, and carotid angioplasty and stent placement. The International Carotid Stenting Study (ICSS), also called Carotid and Vertebral Artery Transluminal Angioplasty Study 2 (CAVATAS 2), the Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy (SPACE) trial, the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, and the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) were five major trials which compared carotid endarterectomy and carotid angioplasty and stent placement. We review the results of the trials and incorporation of the results into clinical decision making.

Critique of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): Flaws in CREST and its Interpretation

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) has been used to support the equivalence of carotid artery stenting (CAS) and carotid endarterectomy (CEA) in the treatment of carotid stenosis in both symptomatic and asymptomatic patients. This inclusion of two different forms of the disease decreased the power and significance of the CREST results and weakened the trial. Other flaws in CREST were the equal weighting of mostly minor myocardial infarctions (MIs) with strokes and death in the peri-procedural, composite ‘end’ point, but not in the 4-year, long-term ‘end’ point. Although CAS was associated with 50% fewer peri-procedural MIs compared with CEA, there were >2.5-fold more MIs after CAS than CEA at 4 years. The 4-year MI rate, however, was not a component of the primary ‘end’ point. Additionally, although the initial CREST report indicated that there was no difference in the outcomes of CAS and CEA according to symptomatic status or sex, subsequent subgroup analyses showed that CAS was associated with significantly higher stroke and death rates than CEA in symptomatic patients, in females and in individuals ≥65 years of age. The present article will examine these and other flaws and the details of CREST's results derived from the trial's preplanned subanalyses to show why the claims that CREST demonstrates equivalence of the two therapeutic procedures are unjustified.

Agreement Between Site-Reported and Ultrasound Core Laboratory Results for Duplex Ultrasound Velocity Measurements in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

Agreement Between Site-Reported and Ultrasound Core Laboratory Results for Duplex Ultrasound Velocity Measurements in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

Bivalirudin for Carotid Artery Stenting

In the past decade, carotid artery stenting (CAS) has been carefully studied as a treatment for symptomatic and asymptomatic carotid artery stenosis. In the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) trial, it was shown that the composite outcome of death, stroke, or myocardial infarction is similar for CAS versus carotid endarterectomy when performed by experienced operators.1 During this time period, significant advances have been made with regards to patient selection and procedural techniques.2 In addition, there have been improvements in embolic protection and stent technology. With these advancements, CAS outcomes have continued to improve with a low rate of periprocedural adverse events observed in numerous single-center and multicenter studies.3–5 Article see p 131 In comparison with recent advances in CAS technology, intraprocedural anticoagulation during CAS has been relatively understudied. The initial randomized studies of CAS, including Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy, Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S), Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE), and the International Carotid Stenting Study (ICSS). all used heparin for adjunctive pharmacotherapy.6–9 In the CREST trial, patients randomized to CAS could be treated with either heparin (86%) or bivalirudin (14%).1 Most of the current evidence for CAS is, therefore, based on using heparin as the intraprocedural anticoagulant. The current societal guidelines for CAS do not make a specific recommendation regarding periprocedural anticoagulation but state that either heparin or bivalirudin may be used.10 A direct thrombin inhibitor, such as bivalirudin, could have significant advantages as an anticoagulant during CAS. Bivalirudin can be administered as weight-based infusion with minimal intraprocedural monitoring and predictable pharmacokinetics. In comparison, heparin has variable between-person pharmacokinetics, and the correct dose of heparin for the goal level of …

Role of carotid artery stenting in the management of severe carotid stenosis

Cardiologia CROATICA Carotid artery stenosis is the cause of 20% to 25% of strokes. The risk of stroke depends upon the severity of the carotid stenosis. According to the NASCET trial, 75% to 94% stenosis is associated with a stroke risk of 27% in symptomatic and 18.5% in asymptomatic patients. Many RCTs have compared the safety and efficacy of CEA with that of CAS in treating carotid artery stenosis, producing conflicting results. The most recent and largest National Institutes of Health-sponsored trial (the Carotid Revascularization Endarterectomy vs. Stenting Trial [CREST]) enrolled both symptomatic and asymptomatic patients and excluded patients with previous disabling stroke or with atrial fibrillation. In contrast to other trials, only one kind of stent and embolic protection filter was allowed and rigorous training criteria were used to standardize operator skill. The rates of stroke, death, and myocardial infarction (MI) were lower than or equal to rates in previous trials for both CAS and CEA. CREST results showed that CAS and CEA were associated with similar rates of death and disabling stroke. In January 2011, the FDA’s Circulatory System Device Panel expanded the indications for CAS in standard-risk patients to include stenosis of ≥70% by ultrasound or ≥50% by angiogram combined with neurologic symptoms, and stenosis of ≥70% by ultrasound or ≥60% by angiogram in the absence of symptoms. In our institution, we performed CAS in 78 patients with stenosis of ≥70% by ultrasound or ≥60% by angiogram. 49 patients were asymptomatic (63%). In all procedures we used a filter wire for embolic protection. Within the 30-day periprocedural period we did not detect any major complication such as death, stroke or MI. In two patients we observed transient ischaemic attack.

Stroke After Carotid Stenting and Endarterectomy in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

Stroke After Carotid Stenting and Endarterectomy in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

Effect of Carotid Revascularization Endarterectomy Versus Stenting Trial Results on Performance of Carotid Artery Stent Placement and Carotid Endarterectomy (P07.251)

Effect of Carotid Revascularization Endarterectomy Versus Stenting Trial Results on Performance of Carotid Artery Stent Placement and Carotid Endarterectomy (P07.251)

Mediators of the Age Effect among Patients Treated with Carotid Artery Stenting: The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) (P02.017)

Mediators of the Age Effect among Patients Treated with Carotid Artery Stenting: The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) (P02.017)

A Post-Hoc Assessment of Current Hormone Therapy on Revascularization Risk in Women: The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) (P03.168)

A Post-Hoc Assessment of Current Hormone Therapy on Revascularization Risk in Women: The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) (P03.168)

Abstract TP124: Mediators of the Age Effect among Patients Treated with Carotid Artery Stenting: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

Background An increased risk of periprocedural stroke and death has been reported for older patients treated with carotid stenting (CAS). Selection of patients for CAS could be improved if patient or artery characteristics responsible for this higher risk could be identified. Methods The 1123 CREST patients randomized to CAS who received CAS within 30-days were analyzed. From the CREST sites, risk factors for atherosclerosis (hypertension, diabetes, and dyslipidemia) and arterial characteristics by angiography (lesion length, eccentric lesions, ulcerated lesions, and percent stenosis) were assessed. From the CREST core labs, potential mediators of the age effect included peak systolic velocity (ultrasound core, available on 853 patients) and arterial characteristics (angiographic core, available on 1042 patients, narrow/no ulcer or wide mouth, lesion location, and distal tortuosity). Mediation analysis assessed impact of adjustment for these factors on the magnitude of the estimated increased risk for CAS at older ages. Results After adjustment for sex and symptomatic status, there was a 1.72-times (95% CI: 1.26 - 2.37) increased risk of periprocedural stroke and death associated with each decade of patient age. Adjustment for lesion length as assessed in the clinical center significantly attenuated this increased risk at older ages to 1.66 (95% CI: 1.20 - 2.29, p = 0.039), an 8.3% attenuation. No other factor showed evidence as a contributor to the periprocedural increased risk of stroke and death in older patients (p &gt; 0.10). Conclusion These data suggest that a longer carotid artery lesion length is a significant contributor to the increased risk of CAS in the elderly. However, attenuation of the age effect was modest, less than a 10% change in the hazard ratios. Other potential mediators such as tortuosity and atherosclerosis of the aortic arch and great vessels were not assessed. Non-anatomic factors that are more common with advancing age such as cerebral white matter disease and subclinical dementia were also not assessed and may play a role in how elderly patients respond to ischemic insults.

Abstract WP160: A Post-Hoc Assessment of Current Hormone Therapy on Revascularization Risk in Women: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

Background: Hormone replacement therapy (HRT) was among factors considered in a post-hoc assessment of the risk of revascularization by carotid artery stenting (CAS) or carotid endarterectomy (CEA) in women enrolled in CREST. Methods: Of the 872 women in CREST, 775 (89%) were post-menopausal and current HRT status was known in 739 (95%). The study composite outcome was defined as any stroke, myocardial infarction, or death during the periprocedural period, plus ipsilateral stroke over a 4-year follow-up period. Treatment groups were combined and differences in the composite outcome were assessed by current HRT at baseline. Results: There were 77/739 (10%) current HRT users. HRT users were more likely to be symptomatic at baseline than non-users (65% vs. 52%; p = 0.027), and were less likely to be diabetic (19% vs. 32%; p = 0.024). However, they were similar in most other factors including age, race, hypertension, dyslipidemia, smoking status, and length of follow-up (p &gt; 0.10). There were no (0) periprocedural events among the 77 HRT users while there were 43 (6.5%) events among the 662 non-users (p = 0.017). Among those event-free at the end of the periprocedural period, there was little evidence of an impact of baseline HRT on the risk of ipsilateral stroke with 2 (2.6%) post-procedural events among 77 HRT users and 12 (1.9%) among 619 non-users. Conclusion: We found that women on current HRT have lower periprocedural risk associated with CAS or CEA than non-users, but little difference in risk after the procedural period. The mechanism for this unexpected finding is elusive. We urge caution in the interpretation of this post-hoc observation and encourage replication or refutation by other revascularization studies with similar data.

Abstract TP145: Effect of Carotid Revascularization Endarterectomy Versus Stenting Trial Results on Performance of Carotid Artery Stent Placement and Carotid Endarterectomy

Introduction: Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) results, published in 2010, showed no difference in outcome between carotid artery stenting (CAS) and carotid endarterectomy (CEA). We aim to determine whether there has been any change in utilization or outcomes of CAS and CEA after CREST results. Methods: We determined the frequency of CAS and CEA procedures performed in the state of Minnesota, in the years 2009 (pre-CREST period) and 2011 (post-CREST period), using data from the Minnesota Hospital Association. Pre- and post-CREST CAS and post-CREST CEA rates and outcomes were compared with pre-CREST CEA (reference). In-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. Results: A total of 2,718 patients underwent CEA or CAS in pre- and post-CREST period. The frequency of CAS increased from 8.2% to 11.5% of the total patients treated (p=0.004). In the pre-CREST period, CAS group (compared with CEA) were younger, had higher rate of diabetes mellitus and congestive heart failure, in-hospital occurrence of urinary tract infection, sepsis, and myocardial infarction. In the post-CREST period, CAS group did not differ from CEA group in demographics, medical co morbidities, or in-hospital complications except UTI. Hospital stay and hospital charges were greater with CAS compared to CEA, however, the differences in 2011 were less than in 2009. After adjusting for age, sex, relevant risk factors and hospital complications, compared with pre-CREST CEA, pre-CREST CAS was associated with higher neurological complications (odds ratio [OR] 3.3; 95% confidence interval [CI] 1.1-10; p=0.03), cardiovascular complications (OR 5.0; 95% CI 1.8-14; p=0.001), and composite outcome of neurological complications, cardiovascular complications, or death (OR 4.0; 95% CI 1.8-8.6; p=0.0007). There was no difference in outcomes or procedure-related complications between post-CREST CAS and either pre- or post-CREST CEA. Conclusion: There has been a significant increase in the number and improvement in outcome of CAS procedures performed after publication of CREST results in state of Minnesota, presumably due to higher rates of CAS performance in average surgical risk patients.

Abstract TMP105: High Utilization Of CAS Procedures Among The Elderly In The Post Crest Era

Background: An important interaction of age with outcome was revealed in Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) where elderly patients ≥70 years had worse outcomes with Carotid stenting (CAS) than with Endarterectomy (CEA). Our hypothesis was that following the CREST study, the proportion of CAS procedures in the elderly would decrease. Methods: We performed a retrospective review of carotid revascularization procedures between June 2009 and April 2012 at a large volume urban medical center. Demographics, indications, surgical high-risk criteria and outcomes of in-hospital stroke/death/MI were collected. Data analysis was performed in subjects over 70 years. Time trends were examined in the post-CREST period. Results: A total of 701 procedures (CEA 36%, CAS 64%) were performed during the study period, of which 360 (51.4%) were in patients ≥70 years (CEA 33%, CAS 67%). A significant proportion (22.1%) was in those ≥80 years. The choice of procedure did not change following CREST. The majority of CAS procedures in elderly (90.8%) were performed by cardiologists. Asymptomatic patients (47.3%) and patients with non-specific symptoms (18.7%) comprised a large proportion of this subgroup. A third of elderly patients with asymptomatic and nonspecific symptoms did not have any surgical high-risk criterion. The proportion of elderly patients receiving CAS for non-specific symptoms increased progressively over time post CREST (27.9% in the most recent months). A similar rise in non-specific indications was noted in the subgroup of patient ≥80 years receiving CAS. About half of this subgroup did not have any surgical high-risk criterion. Conclusion: Two years after CREST results, CAS continues to be performed among the elderly, often for non-specific symptoms or in asymptomatic patients. The lack of a decrease in CAS procedures in the elderly raises questions about whether evidence-based carotid revascularization occurs in the real world.

Abstract WMP106: Increased Carotid Stenting For Nonspecific Symptoms In The Post-crest Era

Background: Nonspecific symptoms such as dizziness and syncope may prompt evaluation of the carotid circulation and detection of carotid stenosis. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) demonstrated equivalent outcomes from Endarterectomy (CEA) and Stenting (CAS) in asymptomatic stenosis. We reviewed the trends in selection and outcomes from revascularization procedures for nonspecific symptoms in the light of CREST results. Methods: We performed a retrospective review of carotid revascularization procedures at a large volume urban medical center, between June 2009 (8 months pre-CREST) and April 2012. Demographics, surgical risk features and in-hospital outcomes of stroke/death/MI were reviewed. Patients were labeled as having nonspecific symptoms when they presented with posterior circulation symptoms or with non-focal symptoms i.e. Dizziness, syncope, etc. To evaluate the effect of CREST, we compared pre CREST (up to Jan 2010) and post CREST cases (Feb 2010 to Apr 2012). Results: 701 procedures (36.1% CEA, 63.9% CAS) were performed and mean age was 70 ±10 years. Non-specific indications accounted for 13% of CEA and 15.9% of CAS. Procedures for nonspecific symptoms did not increase post CREST in the CEA group (12.1% VS 13.3%). They increased significantly in the CAS group (6.3% pre and 18.5% post CREST). Among CAS, the rise was insignificant in the first 8 months (Feb 2010-Sep 2010) post CREST: 7.5%. This rose to 21.2% from Oct 2010 to May 2011: p=0.0017; and 23.8% from June 2011 to April 2012: p=0.0004. The rise in CAS was noted among elderly patients (&gt;70 years), a group in which CREST demonstrated higher complication rates. The rise was noted among both men and women and they did not have surgical high-risk criteria. In-hospital complication rates of stroke/death/MI were 5.6% in this group. Most complications occurred in patients &gt;70 years. Conclusion: CAS for nonspecific symptoms has increased following CREST, and the complication rates associated with these procedures is significant. This raises concern about the value of this procedure. Primary care physicians evaluating non-specific symptoms should obtain neurological expertise prior to revascularization procedures, to allow appropriate patient selection.

Abstract TP156: Re-analysis of the SAPPHIRE and CREST Trials Using Weighted Composite Endpoints

Background: Composite endpoints were used in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) and Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trials to compare outcomes between those who underwent carotid artery stent (CAS) placement and those who underwent carotid endarterectomy (CEA) for treatment of carotid artery disease (CAD). However, using composite endpoints assumes that each individual outcome is of equal clinical importance. Objective: To determine if there was a difference in effectiveness between CAS and CEA in treating CAD if weighted composite endpoints were used in the two randomized trials. Methods: Long-term results were examined for each trial (3 years for SAPPHIRE and 4 years for CREST). Each outcome was given a weighted measure based on a point system [death=5; major stroke=4; minor stroke=2; and myocardial infarction=1]. Study populations were amplified by using a constant coefficient (sum of all points=12). Results were then compared between the CAS and CEA groups to determine statistical significance. Results: At 3 years, there were a total of 56 and 67 adverse outcomes in the CAS and CEA groups, respectively, in the SAPPHIRE trial. At 4 years, there were a total of 215 and 190 adverse outcomes in the CAS and CEA groups, respectively, in the CREST trial. Based on weighted composite endpoints, the CAS group had a significantly lower rate of adverse outcomes compared to the CEA group in the SAPPHIRE trial (p&lt;0.0001) but a significantly higher rate of adverse outcomes in the CREST trial (p&lt;0.0001). Conclusion: With the use of weighted composite endpoints, one can provide more clinically relevant information by discriminating among adverse outcomes and describing differences with greater discriminatory power. Based on weighted composite endpoints, there is clear superiority of CAS over CEA in the SAPPHIRE trial, but the converse is true of results from the CREST trial.

Advances in Stroke

The indications for microsurgery in cerebrovascular pathology have been placed under increased scrutiny, given the continuous refinement of endovascular techniques. Several recent randomized studies and subgroup analyses of concluded studies have been particularly illuminating in this sense and will be the primary focus of this brief review. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) has shown that the risk of perioperative stroke is slightly higher after carotid artery stenting (CAS) than after carotid endarterectomy (CEA), whereas the reverse is true for the risk of periprocedural myocardial infarction.1 Over the past year, the CREST investigators have also reported the results of some prespecified and some ad hoc subgroup analyses. Earlier trials of CAS versus CEA had suggested higher risk of restenosis after endovascular treatment of carotid stenosis compared with CEA. However, in CREST after 2 years, the incidence of restenosis >70% or occlusion was similar in the CAS (6%) and the CEA (6.3%) groups, suggesting that restenosis may not be a major concern if endovascular treatment is contemplated.2 Female sex, diabetes mellitus, and dyslipidemia were associated with higher risk of restenosis in both groups.2 Smoking increased the risk of restenosis in patients undergoing CEA but not after stenting.2 Subgroup analysis by age confirmed that increasing age is associated with a higher risk of periprocedural stroke after CAS but did not affect …

Differential outcomes of carotid stenting and endarterectomy performed exclusively by vascular surgeons in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

Outcomes in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) did not differ between carotid artery stenting (CAS) and carotid endarterectomy (CEA) for the composite primary end point of stroke, myocardial infarction (MI), or death during the periprocedural period or ipsilateral stroke within 4 years. Rigorous credentialing and training of interventionists, including vascular surgeons, were required for the randomization phase of CREST. Because the lead-in phase of CREST had suggested higher perioperative risks after CAS performed by vascular surgeons, the purpose of this analysis was to examine differences in outcomes after randomization between CAS and CEA performed by vascular surgeons. CREST is a prospective randomized controlled trial with blinded end point adjudication. Vascular surgeons performed 237 (21%) of the CAS procedures and 765 (65%) of the CEA procedures among 2320 patients who received their assigned treatment. Proportional hazards analyses were used to estimate the relative efficacy of CAS vs CEA for thecomposite primary end point and also for stroke and death. Among 2502 randomized patients, 1321 (53%) were symptomatic and 1181 (47%) were asymptomatic. For procedures performed exclusively by vascular surgeons, the primary end point did not differ between CAS and CEA at 4-year follow-up (6.2% vs 5.6%, respectively; hazard ratio [HR], 1.30; 95% confidence interval [CI], 0.70-2.41; P= .41) In this subgroup, the periprocedural stroke and death rates were higher after CAS than CEA for symptomatic patients (6.1% vs 1.3%; P=.01). Asymptomatic patients also had slightly higher stroke and death rates after CAS (2.6% vs 1.1%; P= .20), althoughthis difference did not reach statistical significance. Conversely, cranial nerve injuries (0.0% vs 5.0%; P< .001) were lessfrequentafter CAS than CEA. The MI rates were slightly lower after CAS (1.3% vs 2.6%; P= .24). In performing CAS, vascular surgeonshad outcomes for the periprocedural primary end point comparable to the outcomes of all interventionists (HR, 0.99;95% CI, 0.50-2.00) after adjusting for age, sex, and symptomatic status. Vascular surgeons also had similar results after CEA for the periprocedural primary end point compared with other surgeons (HR, 0.73; 95% CI, 0.42-1.27). When performed by surgeons, CAS and CEA have similar net outcomes, although the periprocedural risksvary (lower stroke with CEA and lower MI with CAS). These data suggest that appropriately trained vascular surgeons may safely offer both CEA and CAS for the prevention of stroke. The remarkably low stroke and death rates after CEAperformed by vascular surgeons in CREST, particularly among symptomatic patients, represent the best outcomes ever reported after carotid interventions from a randomized controlled trial. ClinicalTrials.gov identifier: NCT0000473.

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