Carotid Revascularization Endarterectomy Versus Stenting Trial Research Articles

Abstract 48: Early Carotid Endarterectomy and Carotid Artery Stent Placement in Symptomatic Patients With Internal Carotid Artery Stenosis

Background: The American Heart Association/American Stroke Association (AHA/ASA) 2021 guidelines state that in patients in whom revascularization is planned within 1 week of the index stroke, it is reasonable to choose carotid endarterectomy (CEA) over carotid artery stent placement (CAS) to reduce the periprocedural stroke rate (level of evidence 2A, weak evidence, [B-R] moderate quality data). Objective: To compare the 1-month stroke, myocardial infarction (MI), and/or death rates among symptomatic patients undergoing either CAS or CEA according to the timing of the procedure in Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Methods: We analyzed the effect of CAS and CEA on the rates of 1-month stroke, MI, and/or death after adjusting age, gender, presenting symptom (transient ischemic attack [TIA], retinal ischemia, or minor ischemic stroke), severity of stenosis (50-69% and 70-99%), and timing of procedure (≤7 days and >7 days post qualifying event) using multivariate analysis. Results: The rate of 1-month stroke, MI, and/or death was higher (non-significant) in patients who underwent CAS compared with those who underwent CEA within ≤7 days post-qualifying event (8 of 157 [5.1%] versus 3 of 124 [2.4%], p=0.251). In the multivariate analysis, there was no difference in the odds of 1-month stroke, MI, and/or death in patients who underwent CEA compared with those who underwent CAS (odds ratio [OR] 0.57, 95% CI 0.26-1.20, p=0.15). There was no effect of the timing of the procedure (OR 1.19,95% CI 0.48-3.47, p=0.72). The interaction term between CEA versus CAS and the timing of the procedure was not significant (OR 1.69, 95% 0.21-36.31 CI p=0.66). The only significant factors associated with decreased odds of 1-month stroke, MI, and/or death were the qualifying event of TIA (OR 0.13, 95% CI 0.02-0.57, p=0.02) and retinal ischemic event (OR 0.13, 95% CI 0.01-0.63, p=0.02). Conclusions: In our analysis, we did not identify any increase in odds of a 1-month stroke, MI, and/or death rate with CAS compared with CEA according to the timing of the procedure. Qualifying event characteristics rather than the timing of procedure appeared to be the most determinant, highlighting the need to revisit the recommendations in the AHA/ASA guidelines.

Abstract 37: Clopidogrel Bolus Is Inferior To Sustained Clopidogrel Pre-treatment In Patients Undergoing Carotid Artery Stent Placement

Background: Clopidogrel bolus is an option used prior to carotid artery stent placement (CAS) when sustained clopidogrel pre-treatment is not used. Objective: To compare the effect of clopidogrel bolus (450 mg administered ≥4 hours) with sustained clopidogrel pre-treatment (48 hours or greater) prior to CAS in patients prospectively followed over 10 years in Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Methods: The rates of primary endpoint (composite of any stroke, myocardial infarction (MI), or death during the periprocedural period or ipsilateral stroke within 4 years after randomization) were compared between patients who received clopidogrel bolus with those who received sustained clopidogrel pre-treatment after adjusting for age, gender, symptomatic status and initial severity of stenosis (≥70% versus <70%) over 4 years using Cox proportional hazards analysis. Results: The rate of periprocedural stroke (7.3% versus 3.4%, p=0.03) and primary end point (11.3% versus 5.9%, p=0.02) was significantly higher among patients who received clopidogrel bolus. The risk of primary end point was significantly higher in patients who received clopidogrel bolus (hazards ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.4, p=0.02) after adjusting for potential confounders. The overall mean (± SD) primary end point free survival based on Kaplan-Meier analysis was 7.0±0.2 years for patients who received clopidogrel bolus and 8.9±0.1 years for those who received sustained clopidogrel pre-treatment (log-rank test P=0.011). Conclusion: Clopidogrel bolus was associated with higher rates of adverse outcomes compared with sustained clopidogrel pre-treatment in patients who underwent CAS. Therefore, clopidogrel bolus may not be equivalent to sustained clopidogrel pre-treatment.

Carotid endarterectomy remains cost-effective for the surgical management of carotid stenosis

ObjectiveTranscarotid arterial revascularization (TCAR) has gained popularity as an alternative to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS), potentially combining the benefits of a minimally invasive approach with a lower risk of procedural stroke compared with TFCAS. Emerging evidence shows TCAR to have excellent perioperative outcomes. However, the cost-effectiveness of TCAR is not well-understood. MethodsIncorporating data from Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), the Vascular Quality Initiative Surveillance Project, and local cost data, we compared the cost-effectiveness of these three treatment modalities (TFCAS, CEA, and TCAR) for both symptomatic and asymptomatic carotid stenosis using a Markov state-transition model to quantify lifetime costs in United States dollars and effectiveness in quality-adjusted life-years (QALYs). We accounted for perioperative stroke and myocardial infarction, as well as long-term risks of stroke and restenosis. Based on CREST, we assumed a start age of 69 years and a cost-effectiveness acceptability threshold of $100,000/QALYs gained. Sensitivity analyses were performed. ResultsIn the base-case scenario, TCAR cost $160,642/QALY gained compared with CEA, greater than the frequently cited $100,000/QALY gained threshold. TFCAS was more expensive and less effective than other strategies, largely due to a greater periprocedural stroke risk. In one-way sensitivity analysis, if TCAR stroke risk was <0.9% (base-case risk, 1.4%), than it was economically favorable compared with CEA at its current procedural cost. Alternatively, if TCAR procedural costs were reduced by approximately $2000 (base-case cost, $15,182), it would also become economically favorable. In a probabilistic sensitivity analysis, varying all parameters simultaneously over distributions, CEA was favored in 80% of model iterations at $100,000/QALY, with TCAR favored in 19%. ConclusionsAt current cost and outcomes, TCAR does not meet a traditional cost-effectiveness threshold to replace CEA as the primary treatment modality for carotid stenosis. TFCAS is the least cost-effective strategy for carotid revascularization. Given these observations, TCAR should be limited to select patients, specifically those at high physiologic and anatomic risk from CEA. However, TCAR can become cost-effective if its cost is reduced. Given the current outcomes and cost, CEA remains the most cost-effective treatment for carotid revascularization.

Stent-in-Stent Endovascular Correction in Right Internal Carotid Artery Restenosis: a Clinical Case

Background. Carotid artery restenosis is a rare complication of carotid stenting. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) reveals an in-stent restenosis rate of 0–6 %, a fairly low value given an extensive study sampling of patients. Restenosis still lacks an adequate explanation in endovascular carotid surgery. Intravascular ultrasound visualisation, drug-coated balloons, stent reimplantation or reconstructive surgery have actively been used since relatively recently to tackle restenosis. Drug-coated balloons may fail in certain cases due to hampered restenosis angioplasty in a markedly rigid neointimal hyperplasia. Surgical reconstruction also possessed drawbacks, mostly due to obstacles in the stent removal and the procedure infeasibility in high-risk surgical patients.Materials and methods. The article describes a clinical case of stent-in-stent restenosis correction with drug-coated balloon-expandable re-stenting of right internal carotid artery and a long-term prognosis estimation with optical coherence tomography.Results and discussions. This tactic was adopted due to haemodynamically and clinically significant internal carotid artery restenosis, the patient’s denial of carotid endarterectomy and insufficiently effective balloon angioplasty. The choice of the correction technique was conclusive basing on a negative stent deformation testing that showed the lack of deforming stress factors at internal carotid artery restenosis. Intravascular imaging greatly enhances our ability to understand and assess endovascular processes.Conclusion. We consider clinically significant restenoses in previously stented carotid arteries as requiring further research effort, with the clinical case presented describing an individual solution.

Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials.

CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).

Nationwide Trends in Carotid Endarterectomy and Carotid Artery Stenting in the Post-CREST Era.

Background and Purpose- The CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) demonstrated equivalent composite outcomes between carotid endarterectomy (CEA) and carotid artery stenting (CAS) for treating carotid stenosis. We investigated nationwide trends in these procedures and associated periprocedural stroke, myocardial infarction, death, cost, and readmission rates since CREST outcomes were published. Methods- We queried the Nationwide Readmissions Database to identify patients undergoing CEA and CAS for asymptomatic and symptomatic carotid stenosis from 2010 to 2015. Patients were matched based on demographics, comorbidities, and severity of illness. Results- In total, 378 354 CEA and 57 273 CAS patients were treated during this 6-year period. CEA volume decreased by an average of 2669 procedures annually (P=0.001) with stable CAS volume (P=0.225). After matching, CEA patients had a higher rate of periprocedural stroke than CAS patients, driven by increased stroke risk in symptomatic CEA patients (8.1% versus 5.6%; odds ratio, 1.47 [CI, 1.29-1.68]; P<0.001) but a lower rate of overall inpatient mortality (0.8% versus 1.4%; odds ratio, 0.57 [CI, 0.48-0.68]; P<0.001). CEA patients were less likely to be readmitted within 30 days (7.2% versus 8.0%; odds ratio, 0.90 [CI, 0.84-0.96]; P=0.018) and 90 days (12.3% versus 14.1%; odds ratio, 0.86 [CI, 0.81-0.90]; P<0.001), and mean hospital costs were lower for CEA compared with CAS ($14 433 versus $19 172; P<0.001). Conclusions- The procedural treatment of carotid stenosis has changed dramatically in the post-CREST era. When matched for characteristics and illness severity, patients undergoing CEA had a higher rate of perioperative stroke than patients undergoing CAS, primarily among symptomatic patients. These findings are in contrast to the findings of CREST, which showed nearly twice the risk of stroke in CAS patients compared with CEA patients. CEA was associated with lower procedure cost and readmission rate.

Association between perioperative stroke and 30-day mortality in carotid endarterectomy: A meta-analysis

ObjectivesPerioperative stroke is a known complication of carotid endarterectomy (CEA) for patients with symptomatic and asymptomatic carotid stenosis. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) has shown that stroke following CEA is associated with nearly a 3-fold increase in the 4-year mortality compared to patients without such an event. However, no studies to date can establish whether the stroke was the cause of the short term mortality. Thus, our objective is to evaluate if perioperative stroke after CEA increases the risk of 30-day mortality. Patients and MethodsWe performed a meta-analysis of the literature from PubMed and the World Science Database on studies reporting perioperative strokes and 30-day mortality in symptomatic and asymptomatic CEA patients. 3400 articles were retrieved, and abstracts were further screened using the inclusion criteria to obtain a final set of 83 randomized controlled trials and retrospective/prospective studies. ResultsA total of 123,507 CEA procedures were included among the 83 studies. The 30-day perioperative stroke rate for all included studies was 2.15%. The 30-day all-cause mortality rate was 0.93%. In patients with perioperative strokes, the 30-day mortality rate was found to be 17.01%. Among patients without perioperative strokes, the 30-day mortality rate was much lower at 0.57%. The summary odds ratio of perioperative stroke and 30-day mortality was 39.86 (95% CI, 29.30–54.23, p < 0.001). ConclusionPatients with perioperative stroke have an almost 40 times increased risk of 30-day stroke-related mortality. This study highlights the importance of developing a preoperative risk assessment and neuroprotective treatment trial for perioperative stroke.

Immediate and Delayed Procedural Stroke or Death in Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis

The Carotid Stenosis Trialists’ Collaboration pooled data of four randomized trials that recruited patients between 2000 and 2008: Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S), Stent-Protected Angioplasty vs Carotid Endarterectomy (SPACE), International Carotid Stenting Study (ICSS), and Carotid Revascularization Endarterectomy vs Stenting Trial (CREST). Compared with carotid endarterectomy (CEA; 2271 patients), symptomatic patients treated with carotid artery stenting (CAS; 2236) had higher stroke or death rates (4.7% vs 1.9%) the day of the procedure but not during the following 30 days (2.5% vs 2.0%). Age increased the risk of events both the day of the procedure and during follow-up for CAS. The increased procedural stroke or death risk associated with CAS compared with CEA in symptomatic patients is caused by an excess of events occurring the day of the procedure. Procedural safety of CAS needs to be enhanced by technical improvements and increased skill of the operator. Higher age increased the risk for both immediate and delayed events in CAS.

Duration of asymptomatic status and outcomes following carotid endarterectomy and carotid artery stenting in the Carotid Revascularization Endarterectomy vs Stenting Trial

BackgroundMost carotid revascularization studies define asymptomatic as symptom-free for more than 180 days; however, it is unknown if intervention carries similar risk among those currently asymptomatic but with previous symptoms (PS) vs those who were always asymptomatic (AA). MethodsWe compared the periprocedural and 4-year risks of PS vs AA patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) randomized to carotid endarterectomy (CEA) or carotid artery stenting (CAS)/angioplasty. Proportional hazards models adjusting for age, sex, and treatment were used to assess the risk of periprocedural stroke and/or death (S+D; any S+D during periprocedural period), stroke and death at 4 years (any S+D within the periprocedural period and ipsilateral stroke out to 4 years) and the primary end point at 4 years (any stroke, death, and myocardial infarction within the periprocedural period and ipsilateral stroke out to 4 years). Analysis was performed pooling the CEA-treated and CAS-treated patients, and separately for each treatment. ResultsOf 1181 asymptomatic patients randomized in CREST, 1104 (93%) were AA and 77 (7%) were PS. There was no difference in risk when comparing the AA and PS cohorts in the pooled CAS+CEA population for periprocedural S+D (2.0% vs 1.3%), S+D at 4 years (3.6% vs 3.2%), or the primary end point (5.2% vs 5.8%). There were also no differences among those assigned to CEA (periprocedural S+D, 1.5% vs 0%; S+D at 4 years, 2.7% vs 0%; or primary end point, 5.1% vs 2.4%) or CAS (periprocedural S+D, 2.5% vs 2.8%; S+D at 4 years, 4.4% vs 6.9%; or primary end point, 5.3% vs 9.8%) when analyzed separately. ConclusionsIn CREST, only a small minority of asymptomatic patients had previous ipsilateral symptoms. The outcomes of periprocedural S+D, periprocedural S+D, and ipsilateral stroke up to 4 years, and the primary end point did not differ for AA patients compared with PS patients.

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

BackgroundIn 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. MethodsCREST 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). ResultsThe 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. ConclusionsAlthough 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.

Periprocedural Stroke and Myocardial Infarction as Risks for Long-Term Mortality in CREST.

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) previously reported increased mortality in patients who sustained a periprocedural stroke or cardiac event (myocardial infarction [MI] or biomarker only) in follow-up to 4 years. We now extend these observations to 10 years. CREST is a randomized controlled trial designed to compare the outcomes of carotid stenting versus carotid endarterectomy. Proportional hazards models were used to assess the association between mortality and periprocedural stroke, MI, or biomarker-only events. For 10-year follow-up, patients with periprocedural stroke were at 1.74× the risk of death compared with those without stroke (adjusted hazard ratio [HR]=1.74; 95% CI, 1.21-2.50; P<0.003). This increased risk was driven by increased early (between 0 and 90 days) mortality (adjusted HR=14.41; 95% CI, 5.33-38.94; P<0.0001), with no significant increase in late (between 91 days and 10 years) mortality (adjusted HR=1.40; 95% CI, 0.93-2.10; P=0.11). Patients with a protocol MI were at 3.61× increased risk of death compared with those without MI (adjusted HR=3.61; 95% CI, 2.28-5.73; P<0.0001), with an increased hazard both early (adjusted HR=8.20; 95% CI, 1.86-36.2; P=0.006) and late (adjusted HR=3.40; 95% CI, 2.09-5.53; P<0.0001). Patients with a biomarker-only event were at 2.04× increased risk overall (adjusted HR=2.04; 95% CI, 1.09-3.84; P=0.03) than those without MI, with an increased early hazard (adjusted HR=8.44; 95% CI, 1.09-65.5; P=0.04) and a suggestive but nonsignificant association toward higher 91-day to 10-year risk (1.88; 95% CI, 0.97-3.64; P=0.062) contributing to the increased risk. In the CREST trial, patients with periprocedural events demonstrate a substantial increase in future mortality to 10 years. For stroke, this risk is largely confined to an early time frame while periprocedural MI or biomarker-only events confer a continuous increased mortality for 10 years. Strategies to reduce periprocedural events and to optimize the evaluation and management of patients with cardiac events should be considered in efforts to reduce not only early but also long-term mortality. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00004732.

2016–2017 clinical trials in cerebrovascular neurosurgery

Several clinical trials in cerebrovascular neurosurgery were published during 2016–2017. The Collaborative Unruptured Endovascular versus Surgery Trial (CURES) found no difference in outcome between clipping versus coiling of unruptured aneurysms after one year. The Flow Diversion in the Treatment of Intracranial Aneurysm Trial (FIAT) was terminated due to safety concerns. Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity after Subarachnoid Hemorrhage Trial (NEWTON) and other trials demonstrated no improvement in outcome for vasospasm. The Duration of Prophylaxis after Subarachnoid Hemorrhage Trial (DOPAST) did not show benefit for extended seizure prophylaxis. Minimally Invasive Surgery plus Alteplase in Intracerebral Hemorrhage Evacuation Trial (MISTIE) reported a new strategy for treating intracerebral hemorrhage. A hemorrage site analysis from the Japan Adult Moyamoya Trial (JAM) was presented. The 10-year results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) and the new Asymptomatic Carotid Trial I (ACT I) were reported. Lastly, findings from six ischemic stroke trials were presented.

Trials and Frontiers in Carotid Endarterectomy and Stenting.

Based on the strength of randomized trials from the 1990s, major societal guidelines recommend carotid endarterectomy (CEA) for severe (≥70%), symptomatic carotid stenosis if an operative stroke/death rate of <6% can be maintained (history and major trials in carotid revascularization are summarized in the online-only Data Supplement).1–4 Though the benefit is less evident, most guidelines also recommend consideration of CEA for 50% to 69% symptomatic stenosis.2–4 There are subtle differences in recommendations regarding carotid artery stenting (CAS) in symptomatic patients. Some guidelines stipulate that CEA should be preferred over CAS in patients with severe (≥70%) symptomatic carotid stenosis,2,5 especially if >70 years old,4 whereas others position CAS as an alternative.1,3 Though the risk of operative stroke/death is higher with CAS, major randomized clinical trials (RCTs) report event rates under the recommended 6% cutoff for both treatment modalities. Regarding asymptomatic disease, CEA is recommended for patients with stenosis ≥60% to 70% in highly selected patients as long as operative stroke/death rates <3% can be maintained.1 A predicted life expectancy of at least 3 to 5 years has also been suggested.2 The 3% threshold has been easily met by CEA cohorts in the CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial; 1.4%)6 and the ACT1 (Asymptomatic Carotid Trial; 1.7%),7 suggesting that an even lower threshold may be appropriate. Controversially, some guidelines have recommended that CAS can be considered in highly selected patients with asymptomatic carotid stenosis ≥60% to 70%,1,4,8 whereas others argue that the evidence remains insufficient.2 The lack of consensus in the management of asymptomatic carotid stenosis is reflective of an ongoing need for high-quality RCT data to guide practice. ### CEA Operative Stroke Risk and High Risk Designation Most clinical trials in carotid revascularization have focused …

National Patterns of Carotid Revascularization Before and After the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST)

The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) showed greater safety of carotid artery stenting (CAS) in patients younger than 70 years and carotid endarterectomy (CEA) in those older than 70 years. It is unknown how the result of CREST has influenced carotid revascularization choices in the United States. To evaluate national patterns in CAS performance in patients older than 70 years in the post-CREST (2011-2014) compared with the pre-CREST (2007-2010) era. All adults older than 70 years undergoing carotid revascularization in the United States from 2007 to 2014 were retrospectively identified from the 2007-2014 National Inpatient Sample using International Classification of Disease, Ninth Revision procedural codes. From 61 324 882 unweighted hospitalizations contained in the 2007-2014 National Inpatient Sample, 494 733 weighted carotid revascularization admissions in adults older than 70 years were identified using International Classification of Disease, Ninth Revision procedural codes. The proportion of CAS performed in all age groups over time was estimated and multivariable-adjusted models were used to compare the odds of receiving CAS in the pre-CREST with those in the post-CREST era in adults older than 70 years. A total of 41.8% of all patients were women, and mean (SE) age at presentation was 78.1 (0.03) years. A total of 16.3% of CAS and 10.1% of CEA procedures were performed in patients with symptomatic stenosis. The proportion of patients older than 70 years receiving CAS increased from 11.9% in the pre-CREST to 13.8% in the post-CREST era (P = .005). In multivariable models, the odds of receiving CAS increased by 13% in all patients older than 70 years in the post-CREST compared with the pre-CREST period (odds ratio [OR], 1.13, 95% CI, 1.00-1.28, P = .04), including symptomatic women (OR, 1.31, 1.05-1.65, P = .02). Symptomatic stenosis (OR 1.39; 95% CI, 1.27-1.52; P < .001), congestive heart failure (OR, 1.48; 95% CI, 1.35-1.63; P < .001), and peripheral vascular disease (OR, 1.35; 95% CI, 1.27-1.43; P < .001) were associated with higher odds of CAS; comorbid hypertension (OR, 0.70; 95% CI, 0.66-0.74; P < .001), smoking (OR, 0.84; 95% CI, 0.78-0.91; P < .001), and weekend admission (OR, 0.77; 95% CI, 0.68-0.88; P < .001) were negatively associated with the odds of CAS. Despite concerns for higher periprocedural complications with CAS in elderly patients, the odds of CAS increased in the post-CREST compared with pre-CREST era in patients older than 70 years, including symptomatic women.

The association of Carotid Revascularization Endarterectomy versus Stent Trial (CREST) and Centers for Medicare and Medicaid Services Carotid Guideline Publication on utilization and outcomes of carotid stenting among “high-risk” patients

ObjectiveSince the 2004 approval by the United States Food and Drug Administration of carotid artery stenting (CAS), there have been two seminal publications about CAS reimbursement (Centers for Medicare and Medicaid Services guidelines; 2008) and clinical outcomes (Carotid Revascularization Endarterectomy versus Stent Trial [CREST]; 2010). We explored the association between these publications and national trends in CAS use among high-risk symptomatic patients. MethodsThe most recent congruent data sets of the Nationwide Inpatient Sample (NIS) were queried for patients undergoing carotid revascularization. The sample was limited to include only patients who were defined as “high-risk” if they had a Charlson Comorbidity Score of ≥3.0. Subgroup analyses were performed of high-risk patients with symptomatic carotid stenosis. Utilization proportions of CAS were calculated quarterly from 2005 to 2011 for NIS. Three time intervals related to Centers for Medicare and Medicaid Services guidelines and CREST publication were selected: 2005 to 2008, 2008 to 2010, and after 2010. Logistic regression with piecewise linear trend for time was used to estimate different trends in CAS use for the overall high-risk sample and for neurologically asymptomatic and symptomatic cases. Multivariate logistic regression was used to compare odds of postoperative mortality and stroke between these two procedures at different time intervals independent of confounding variables. ResultsDuring the study period, 20,079 carotid endarterectomies (CEAs) and 3447 CAS procedures were performed in high-risk patients in the NIS database. CAS utilization constituted 20.5% of carotid revascularization procedures among high-risk symptomatic patients, with a significant increase from 18.6% to 24.4% during the study period (P < .001). There was an initial increase during 2005 to 2008 in the rate of CAS compared with CEA, CAS utilization significantly decreased during 2008 to 2010 by a 3.3% decline in the odds ratio (OR) of CAS per quarter (OR, 0.967; 95% confidence interval [CI], 0.943-0.993; P = .002), and after CREST (after 2010), CAS utilization continued to increase significantly from the prepublication to the postpublication time interval. The odds of in-hospital mortality (OR, 2.56; 95% CI, 1.17-5.62; P = .019) and postoperative in-hospital stroke (OR, 1.53; 95% CI, 1.09-3.68; P = .024) were independently and significantly higher for CAS patients in the overall sample. ConclusionsThe use of CAS for carotid revascularization in a high-risk cohort of patients has significantly increased from 2005 to 2011. Compared with CEA, CAS independently increased the odds of perioperative in-hospital stroke in all high-risk patients and of in-hospital mortality in symptomatic high-risk patients.

National Patterns of Carotid Revascularization in the Pre- and Post- Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) Era (S36.001)

National Patterns of Carotid Revascularization in the Pre- and Post- Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) Era (S36.001)

CREST-2: Identifying the Best Method of Stroke Prevention for Carotid Artery Stenosis: National Institute of Neurological Disorders and Stroke Organizational Update.

One of the great achievements of modern medicine is the successful prevention of stroke and other cardiovascular diseases. Although the incidence of stroke has substantially declined over the last 30 years, ≈200 000 preventable stroke deaths still occur annually in the United States. According to a recent study based on the Greater Cincinnati/Northern Kentucky Stroke Study, annually ≈41 000 strokes in the United States are attributed to extracranial internal carotid artery stenosis. Early revascularization for symptomatic carotid stenosis—that is, in patients with recent ipsilateral stroke or TIA—is well established as effective at preventing ipsilateral stroke. Carotid stenosis in the absence of symptoms is extremely common, but the best treatment is unclear. While 2 randomized trials showed a benefit of carotid endarterectomy (CEA) over antiplatelet therapy with aspirin, the number needed to treat approaches 200. Does aggressive risk factor control change that balance? Population screening for carotid stenosis followed by revascularization is considered to cause net harm. Are complication rates from endarterectomy and stenting now low enough to justify expanding their indications in asymptomatic patients? The National Institute of Neurological Disorders and Stroke (NINDS)–funded CREST-2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) is an ambitious attempt to further refine the treatment of asymptomatic carotid stenosis. As one of the largest randomized stroke prevention trials, the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) was designed to compare the safety and efficacy of 2 stroke prevention procedures for carotid artery narrowing—CEA and carotid artery stenting (CAS)—in symptomatic and asymptomatic individuals. Starting in December 2000, this NINDS-funded trial enrolled >2500 patients at 117 sites in the United States and Canada. Because of slow enrollment, the trial took 9 years to complete. In 2010, the results of CREST indicated that the 2 revascularization procedures were equivalent for …

Abstract TP121: National Patterns of Carotid Revascularization in the Pre- and Post- Crest Era

Background: The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) showed greater safety of carotid artery stenting (CAS) in patients (pts) &lt;70 yo and endarterectomy (CEA) in &gt;70 yo. The aim of this study was to evaluate national patterns in CAS performance in pts &gt;70yo in the pre- (2007-2010) and post-CREST (2011-2013) era. Methods: Adults requiring CAS or CEA were identified from the 2007-2013 Nationwide Inpatient Sample (NIS) using International Classification of Disease (ICD-9) codes. We estimated the proportion of CAS performed in all age groups and used multivariate models adjusted for clinical and hospital factors to compare odds of receiving CAS in the pre- to post-CREST era. Results: We identified 839,357 weighted cases of CAS and CEA from the NIS. 15.7% of CAS and 8.4% of CEA were performed in symptomatic pts. CAS increased in all age groups over time (figure 1). Proportion of &gt;70yo receiving CAS increased from 11.9% in the pre- to 13.9% in the post-CREST era (p=0.004). In multivariate models, odds of receiving CAS as opposed to CEA increased by 15% in all pts &gt;70yo in the post-CREST compared to the pre-CREST period (OR 1.15, 95%CI 1.10-1.19, p&lt;0.001) including asymptomatic women (OR 1.10, 1.03-1.18). Congestive heart failure (OR 1.50, 95%CI 1.41-1.60), peripheral vascular disease (OR 1.41, 95%CI 1.34-1.48) and hospitalization in the Western region as opposed to the Northeast (OR 1.25, 95%CI 1.16-1.34) were associated with higher odds of CAS in pts&gt;70yo, while female sex (OR 0.92, 95%CI =0.89-0.97), smoking (OR 0.84, 95%CI 0.79-0.90) and weekend admission (OR 0.78, 95%CI 0.70-0.86) were negatively associated with odds of CAS. Conclusion: Rates of CAS increased in the post- compared to pre-CREST era in pts &gt;70yo including asymptomatic women. Despite the concerns of higher periprocedural complications with CAS in elderly pts, the results of CREST have not influenced clinical revascularization practice in pts &gt;70yo.

Abstract 208: Periprocedural Stroke and Myocardial Infarction as Risks for Long-term Mortality in CREST

Introduction: Occurrence of stroke and myocardial infarction (MI) after carotid endarterectomy or stenting have each been associated with increased later mortality. Methods: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) 69 strokes, 37 protocol MIs, and 19 biomarker + only events occurred within 30 days among 2272 patients followed up to 10 years. Mortality was determined and compared for patients with stroke, MI, or biomarker + only to those without. Cox proportional hazard models adjusting for age, sex, symptomatic status and treatment were calculated to assess the relationship between mortality and stroke and mortality and MI status. Kaplan-Meier survival curves were plotted. Results: Patients with peri-procedural stroke had a 67% greater likelihood of long-term mortality compared to those without stroke (HR=1.67, 95% CI 1.15,2.43; p&lt;0.007)(Figure A). Patients with a protocol MI had a 249% greater likelihood of mortality, and biomarker+ only patients had a 104% greater likelihood of mortality, compared to those without MI (HR=3.49; 95%CI 2.20,5.53, p&lt;0.0001; and HR=2.04; 95% CI 1.09,3.83, p=0.03)(Figure B). Discussion: Stroke, MI, and biomarker + only events following CEA or CAS are associated with increased long-term mortality. The higher risk for MI may be a marker for patients with serious underlying heart disease, rather than causal, providing an opportunity to decrease long-term mortality through aggressive diagnostic evaluation and preventive treatment.

The year in cardiology 2016: peripheral circulation.

In an epidemiological update in 2016, cardiovascular (CV) disease has been estimated as cause of 45% of deaths in Europe, including 12% due to stroke and 14% to other CV diseases, highlighting the major burden of non-coronary artery diseases (i.e. aorta, carotid, and lower extremity arteries) and venous thromboembolism (VTE) in our continent ( Figure 1 ).1 Similar to previous years,2,3 relevant scientific evidence in these fields was brought out in 2016 which will affect our daily clinical practice. Figure 1 Proportion of all deaths due to major causes in Europe, latest available year (adapted from Townsend).1 In the new ‘2016 European guidelines on cardiovascular disease prevention in clinical practice’, the usefulness of carotid intima-media thickness to stratify CV risk has been strikingly challenged, and this marker is no longer recommended due to its high variability, low intra-individual reproducibility, and lack of added predictive value, even in intermediate risk subjects.4 In opposition, carotid plaque remains a valuable tool for CV risk stratification. In 2016, the long-term clinical equipoise of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) was confirmed by the 10 year analysis of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), reporting similar rates of death, stroke, or MI within 30 days, or ipsilateral stroke up to 10 years for both strategies (11.8% vs. 9.9%; P = 0.51) ( Table 1 ).5 View this table: Table 1 Summary of major randomized trials in the aorta, peripheral artery diseases, and venous thrombo-embolic disease in 2016 Peri-procedural stroke during CAS is often related to plaque embolization. The randomized Asymptomatic Carotid Trial (ACT) I compared CAS with embolic protection to CEA in 1453 patients with asymptomatic carotid stenosis, not considered at high surgical risk ( Table 1 ).6 The composite endpoint of death, stroke, or MI at 30 days, or ipsilateral stroke at 1 year, was non-inferior in CAS …