Carotid Revascularization Endarterectomy Research Articles

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.

Prediction Models for Clinical Outcome After a Carotid Revascularization Procedure.

Background and Purpose- Prediction models may help physicians to stratify patients with high and low risk for periprocedural complications or long-term stroke risk after carotid artery stenting or carotid endarterectomy. We aimed to evaluate external performance of previously published prediction models for short- and long-term outcome after carotid revascularization in patients with symptomatic carotid artery stenosis. Methods- From a literature review, we selected all prediction models that used only readily available patient characteristics known before procedure initiation. Follow-up data from 2184 carotid artery stenting and 2261 carotid endarterectomy patients from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]) were used to validate 23 short-term outcome models to estimate stroke or death risk ≤30 days after the procedure and the original outcome measure for which the model was developed. Additionally, we validated 7 long-term outcome models for the original outcome measure. Predictive performance of the models was assessed with C statistics and calibration plots. Results- Stroke or death ≤30 days after the procedure occurred in 158 (7.2%) patients after carotid artery stenting and in 84 (3.7%) patients after carotid endarterectomy. Most models for short-term outcome after carotid artery stenting (n=4) or carotid endarterectomy (n=19) had poor discriminative performance (C statistics ranging from 0.49-0.64) and poor calibration with small absolute risk differences between the lowest and highest risk groups and overestimation of risk in the highest risk groups. Long-term outcome models (n=7) had a slightly better performance with C statistics ranging from 0.59 to 0.67 and reasonable calibration. Conclusions- Current models did not reliably predict outcome after carotid revascularization in a trial population of patients with symptomatic carotid stenosis. In particular, prediction of short-term outcome seemed to be difficult. Further external validation of existing prediction models or development of new prediction models is needed before such models can be used to support treatment decisions in individual patients.

An Increased Fear in Cardiovascular Patients for Strokes Versus Non-Fatal Myocardial Infarctions and its Implication on Carotid Revascularization Decision-Making

ABSTRACT Endovascular stenting of the carotid artery continues to incite debate among practitioners regarding its superiority over the traditional approach of carotid endarterectomy for reduction of stoke incidence. The 2013 Carotid Revascularization Endarterectomy versus Stenting Trial concluded there was no difference between the two techniques as carotid endarterectomy increased the prevalence of a nonfatal myocardial infarction while a higher incidence of strokes was observed after carotid stenting. The inclusion of myocardial infarction as part of the primary endpoint has drawn criticism; however, in this dispute, a key component is missing: the patient's perspective. A patient's values and fears are crucial to the choice between therapies carrying different risks. We surveyed 500 cardiovascular patients using a qualitative scale (from 1, not at all fearful, to 5, very fearful) to determine their level of fear of stroke, non-fatal myocardial infarction, and limb amputation as well as their understand...

Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

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 TMP34: The Challenge and Yield of Racially and Ethnically Diverse Patient Populations in Low Event-Rate Clinical Trials

Background: Concern for underrepresentation of minorities in clinical trials has focused on enrollment proportions and generalizability. The interplay of trial event-rates with diversity has not been emphasized. Methods: The Carotid Revascularization Endarterectomy vs Stent Trial (CREST) randomized 2502 patients and compared them by race, ethnicity, baseline characteristics, and primary outcome (any peri-procedural stroke, death or MI and subsequent ipsilateral stroke up to 10 years); those with unknown race or ethnicity were excluded. Proportional hazards models adjusting for age, sex, symptomatic status and treatment were used to test for a treatment by race/ethnicity interaction. Results: One-hundred-nine patients (4.4%) were black, 32 (1.3%) Asian, 2332 (93.4%) white, 11 (0.4%) other by self-report, and 18 (0.7%) unknown; 90 (3.6%) were Hispanic, 2377 (95%) non-Hispanic, and 35 (1.4%) unknown. Compared to whites, racial minorities were younger (mean age 67±8.9 vs 69±8.8, p=0.004), more often female (44% vs 34%, p=0.01), symptomatic (63 vs 52%, p=0.01), and diabetic (51% vs 29%, p&lt;0.0001), but less often dyslipidemic (76% vs 85%, p=0.004), current smokers (19% vs 27%, p=0.04), or had a history of cardiovascular disease (34% vs 46%, p=0.007). Hispanics were more often diabetic (48% vs 30%, p=0.0002). The rate of the primary endpoint was 10.9%±0.9% at 10 years, and did not differ by race or ethnicity (p inter &gt;0.24). In the context of this low rate, even if minority recruitment were increased to represent 50% of study participants, and if the treatment difference in one race were a greater hazard of HR = 1.49 (anticipated alternative hypothesis), then the hazard ratio in the other group would need to be &lt;0.73, or &gt;3.31, to have 90% power of detection. Conclusions: The proportion of racial and ethnicity participation in CREST was suboptimal at &lt; 10%. Primary outcomes did not differ by minority or ethnic status. However, in low event-rate trials very high and even unrealistic enrollment goals for diversity, for example ≥50%, may still be insufficient for detection of outcome differences by race or ethnicity.

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.

Which patients with asymptomatic carotid stenosis benefit from revascularization?

To summarize why there are polarized opinions regarding the management of patients with asymptomatic carotid disease and whether it is possible to identify patients who might benefit from carotid interventions. Carotid Revascularization Endarterectomy Versus Stenting Trial and Asymptomatic Carotid Trial 1 (ACT-1) recently concluded that outcomes after carotid endarterectomy and carotid stenting were not significantly different in asymptomatic patients and that procedural risks were below the accepted 3% threshold. However, systematic reviews suggest that Carotid Revascularization Endarterectomy Versus Stenting Trial/ACT-1 results may not be generalizable into routine practice. In parallel, meta-analyses suggest that stroke rates on medical therapy may be declining, suggesting that Asymptomatic Carotid Atherosclerosis Study/Asymptomatic Carotid Surgery Trial data, which have underpinned every practice guideline since 1995, are too historical for use in 2017. A recent review has, however, identified a number of clinical/imaging features that may be associated with higher rates of stroke on medical therapy. The majority of surgeons/interventionists are unlikely to accept radical changes in practice until new randomized trials confirm that the risk of stroke on modern medical therapy is significantly lower than that previously accepted. In the interim, it would be preferable to target interventions into a smaller cohort who present with clinical/imaging features that might render them 'higher risk for stroke' on medical therapy.

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 …

Long-Term Outcomes of Carotid Artery Stenting in Clinical Practice.

There is a lack of long-term data and data outside of controlled clinical trials in carotid artery stenting. Thus, we sought to evaluate the long-term effectiveness in stroke prevention by carotid artery stenting in a large number of patients in a real-world setting. The present work represents an all-comer registry with a strict, prospectively designed, follow-up protocol, including an independent pre- and postprocedural neurological assessment. Between November 1999 and March 2015, 1000 procedures in 901 patients were consecutively performed in a single center. Mean age was 71±9 years, and symptomatic stenosis was present in 262 patients (29.1%). The population was also characterized by a high comorbidity: 289 patients (32.1%) would have been excluded according to the CREST protocol (Carotid Revascularization Endarterectomy Versus Stent Trial). The median length of follow-up was 5.5 (interquartile range, 2.6-7.9) years and complete in 93% of the patients. The rate of the primary end point (composite of stroke, death, and myocardial infarction [major adverse cardiac or cerebrovascular event] by day 30 plus ipsilateral stroke beyond 30 days) was 6.9% (9.9% in symptomatic versus 5.7% in asymptomatic patients; P=0.03). The rate was higher in CREST ineligible than in CREST eligible patients (11.4% versus 4.9%; P=0.001). Long-term stroke prevention by carotid artery stenting is effective in experienced centers. A high percentage of patients who would have been excluded from controlled clinical trials undergoes carotid artery stenting in daily clinical practice. However, these patients have a substantially higher risk for an acute major adverse cardiac or cerebrovascular event.

Carotid Stenting Versus Carotid Endarterectomy: What Did the Carotid Revascularization Endarterectomy Versus Stenting Trial Show and Where Do We Go From Here?

Although rapidly expanding in its use, carotid artery stenting remains a relatively new procedure. Its growth is due, at least in part, to the perceived advantages of a less invasive technique. However, the clinical effectiveness and specific role for stenting in the treatment of carotid occlusive disease are still under evaluation. The primary aim of the randomized clinical trial, Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), was to contrast the relative efficacy of carotid stenting versus carotid endarterectomy in preventing stroke, myocardial infarction, or death during a 30-day periprocedural period or ipsilateral stroke over the follow-up period in patients with symptomatic and asymptomatic extracranial carotid stenosis. The secondary goals were to describe the differential efficacy of the 2 procedures in men and women, contrast periprocedural (30-day) morbidity and postprocedural morbidity and mortality, estimate and contrast the restenosis rates of the 2 procedures, evaluate differences in measures of health-related quality of life and cost-effectiveness, and identify subgroups of participants at differential risk of stenting or surgery. This report summarizes the results obtained from CREST with respect to its primary and secondary aims.

Transcranial Doppler Emboli Identifies Asymptomatic Carotid Patients at High Stroke Risk: Why This Technique Should be Used More Widely.

With modern intensive medical therapy, the annual risk of ipsilateral stroke in asymptomatic carotid stenosis (ACS) is now ∼0.5%. Therefore, even the relative low risks reported from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) trial do not justify routine intervention in most (90%) of the patients with ACS. It is therefore necessary to identify the ∼10% to15% of patients with ACS who have a stroke risk high enough to justify intervention. Transcranial Doppler (TCD) embolus detection has been shown in 2 prospective studies (one with 468 patients and the other with 467 patients) to identify patients at high risk and distinguish them from those who would be better served by medical therapy. There is no valid reason why carotid intervention should be carried out in ACS without first identifying that the patient's risk of stroke is higher than the risk of intervention. The best validated way to do this is by TCD embolus detection, and the cost of TCD equipment and training is approximately the same as the cost of 2 carotid stenting procedures in the United States. This procedure should be used more widely.

Autonomic outcome is better after endarterectomy than after stenting in patients with asymptomatic carotid stenosis

Carotid endarterectomy and stenting have comparable efficacy in stroke prevention in asymptomatic carotid stenosis. In patients with carotid stenosis, cardiac events have a more than threefold higher incidence than cerebrovascular events. Autonomic dysfunction predicts cardiovascular morbidity and mortality, and carotid stenosis interferes with baroreceptor and chemoreceptor function. We assessed the effect of elective carotid revascularization (endarterectomy vs stenting) on autonomic function as a major prognostic factor of cardiovascular health. In 42 patients with ≥70% asymptomatic extracranial carotid stenosis, autonomic function was determined by analysis of heart rate variability (total band power [TP], high frequency band power [HF], low-frequency band power [LF], very low frequency band power [VLF]), baroreflex sensitivity (αHF, αLF), respiratory chemoreflex sensitivity (central apnea-hypopnea index), and cardiac chemoreflex sensitivity (hyperoxic TP, HF, LF, and VLF ratios) before and 30days after revascularization. Patients with endarterectomy were older than patients with stenting (69± 7 vs 62± 7years; P ≤ .008) but did not differ in gender distribution and preintervention autonomic function. Compared with stenting, postintervention heart rate variability was higher (ln TP, 6.7 [95% confidence interval (CI), 6.3-7.0] vs 6.1 [95% CI, 5.8-6.5; P ≤ .009]; ln HF, 4.5 [95% CI, 4.1-5.0] vs 4.0 [95% CI, 3.4-4.5; P ≤ .05]; ln VLF, 6.0 [95% CI, 5.7-6.4] vs 5.5 [95% CI, 5.2-5.9; P≤.02]); respiratory chemoreflex sensitivity (central apnea-hypopnea index, 5.5 [95% CI, 2.8-8.2] vs 10.0 [95% CI, 6.9-13.1; P ≤. 01]) and cardiac chemoreflex sensitivity (TP ratio, 1.2 [95% CI, 1.1-1.3] vs 1.0 [95% CI, 0.9-1.0; P ≤ .0001]; HF ratio, 1.4 [95% CI, 1.2-1.5] vs 0.9 [95% CI, 0.8-1.1; P ≤ .001]; LF ratio, 1.5 [95% CI, 1.3-1.6] vs 1.0 [95% CI, 0.8-1.1; P ≤ .0001]; VLF ratio, 1.2 [95% CI, 1.1-1.3) vs 1.0 [95% CI, 0.9-1.1; P ≤ .002]) were lower after endarterectomy. Postintervention baroreflex sensitivity did not differ after endarterectomy and stenting. Autonomic function was better after endarterectomy than after stenting. Better autonomic function after endarterectomy was based on restoration of chemoreceptor but not baroreceptor function and may improve cardiovascular long-term outcome.