Comprehensive Evaluation and Management Strategies for Asymptomatic Carotid Artery Stenosis: A Critical Review and Network Meta-Analysis.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial

Optimal Management of Asymptomatic Carotid Artery Stenosis: A Systematic Review and Network Meta-Analysis

Carotid artery disease is a major cause of ischemic stroke, the risk of which is directly related to the severity of stenosis and presence of symptoms.1,2 Stroke is the third leading cause of death in the United States, with approximately three quarters of a million strokes per year. Stroke is the leading cause of functional impairment, with more than 20% of survivors requiring institutional care and up to one third having a permanent disability.3 More worrisome, however, is the fact that as the population ages, the number of patients having strokes appears to be increasing.4 The pathophysiology of stroke may be broadly classified as hemorrhagic, embolic, or ischemic. The majority of strokes are caused by embolic events due to atheroemboli from the carotid artery, the ascending aorta, and arch vessels or cardiac thromboembolism from the left atrium or ventricle. It is estimated that carotid artery stenosis is responsible for 15% to 20% of all strokes.5 As percutaneous treatment options expand, there is uncertainty about appropriate therapy for carotid disease. This document will focus on 3 current controversies: (1) carotid artery revascularization in asymptomatic patients, (2) carotid artery stenting (CAS) in patients who are considered to be at increased surgical risk for carotid endarterectomy (CEA), and (3) the current role for CAS in patients at average surgical risk. ### Prevalence and Natural History The prevalence of asymptomatic extracranial carotid stenosis (≥50%) in persons >65 years of age is estimated to be between 5% and 10%, whereas ≤1% of patients are estimated to have a severe narrowing (>80%).6 In asymptomatic patients with ≥50% carotid artery stenoses, the annual risk of stroke is between 1% and 4.3%.2,7 Long-term (10- to 15-year) cohort studies in asymptomatic patients with moderate to severe carotid stenosis demonstrate an ipsilateral stroke rate between 0.9% and 1.1% per …

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses

BackgroundTreatment of individuals with asymptomatic carotid artery stenosis is stillhandled controversially. Recommendations for treatment of asymptomaticcarotid stenosis with carotid endarterectomy (CEA) are based on trialshaving recruited patients more than 15 years ago. Registry data indicatethat advances in best medical treatment (BMT) may lead to a markedlydecreasing risk of stroke in asymptomatic carotid stenosis. The aim of theSPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effectsof BMT alone with that of BMT in combination with CEA or carotid arterystenting (CAS), respectively, in patients with asymptomatic carotid arterystenosis of ≥70% European Carotid Surgery Trial (ECST) criteria.MethodsSPACE-2 is a randomized, controlled, multicenter, open study. A majorsecondary endpoint was the cumulative rate of any stroke (ischemic orhemorrhagic) or death from any cause within 30 days plus an ipsilateralischemic stroke within one year of follow-up. Safety was assessed as therate of any stroke and death from any cause within 30 days after CEA or CAS.Protocol changes had to be implemented. The results on the one-year periodafter treatment are reported.FindingsIt was planned to enroll 3550 patients. Due to low recruitment, theenrollment of patients was stopped prematurely after randomization of 513patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113).The one-year rate of the major secondary endpoint did not significantlydiffer between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well asrates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-causemortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of allstrokes occurred in the peri-interventional period. Higher albeitstatistically non-significant rates of restenosis occurred in the stentinggroup (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increasedstroke rates.InterpretationThe low sample size of this prematurely stopped trial of 513 patients impliesthat its power is not sufficient to show that CEA or CAS is superior to amodern medical therapy (BMT) in the primary prevention of ischemic stroke inpatients with an asymptomatic carotid stenosis up to one year aftertreatment. Also, no evidence for differences in safety between CAS and CEAduring the first year after treatment could be derived. Follow-up will beperformed up to five years. Data may be used for pooled analysis withongoing trials.

P rimarily on the basis of data derived from the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, 1 the US Food and Drug Administration (FDA) has approved the use of carotid stents (CASs) in high-risk patients.The SAPPHIRE trial was published and much heralded as a randomized trial demonstrating that CASs were not inferior to carotid endarterectomy (CEA).Yet, the more recent Endarterectomy Versus Angioplasty in Patients with Symptomatic Carotid Stenosis randomized trial of CASs compared with CEA had to be stopped because the stroke rate with stents was so high that it triggered the safety guidelines of the study design. 2How can we explain the striking difference in outcome between these 2 studies, and how did it happen that the FDA was so convinced of the quality and validity of the SAPPHIRE trial that it granted approval for CASs?An examination of the SAPPHIRE trial-its conduct, data collection and analysis, the circumstances of publication, the presentation to the FDA Advisory Panel, and its consequent approval-is the primary focus of this article.This is a case study of the flaws in our system for the evaluation and approval of medical devices that warrant serious reflection on our ability to properly create and act on accurate information and live up to our commitment to evidence-based decision making. Response by Samuelson et al p 1601As it now stands, existing studies leave us with the unfortunate but not unreasonable conclusion that no scientific basis exists for the use of CASs as approved by the FDA, and in the absence of change, there is every reason to doubt the capability of our current system to protect the public from unnecessary risk in the future.Although this article focuses on just 1 example of how our systems are flawed at multiple levels to provide a reliable assessment of CASs and other technology, readers seeking further examples can find a wealth of related information.

BackgroundAsymptomatic carotid artery stenosis (ACS) can be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or best medical treatment (BMT) only. For all treatment options, optimization of vascular risk factors such as arterial hypertension, hyperlipidemia, smoking, obesity, and insufficient physical activity is essential. Data on adherence to BMT and lifestyle modification in patients with ACS are sparse. The subject of this investigation is the implementation and quality of risk factor adjustment in the context of a randomized controlled trial.MethodsA total of 513 patients in the prematurely terminated, randomized, controlled, multicenter SPACE-2 trial (ISRCTN 78592017) were analyzed within one year after randomization into 3 groups (CEA, CAS, and BMT only) for implementation of prespecified BMT recommendations and lifestyle modifications. Measurement time points were the screening visit and visits after one month (D30), 6 months (M6), and one year (A1). Differences between groups and follow-up visits (FUVs) relative to the screening visit were investigated.FindingsFor all FUVs, a significant increase in statin medication (91% at A1; p < 0.0001) was demonstrated to be associated with a significant decrease (p < 0.01) in cholesterol levels (median 167 mg/dl at A1) and LDL cholesterol levels (median 93 mg/dl at A1). The lowest cholesterol levels were achieved by patients in the BMT group. Seventy-eight percent of all patients reached predefined target cholesterol levels (< 200 mg/dl), with significantly better rates in the BMT group (p = 0.036 at D30). Furthermore, a significant decrease in arterial blood pressure at all FUVs (p < 0.05) was associated with a significant increase in antihypertensive medication (96% at A1, p < 0.0001). However, only 28% of patients achieved the predefined treatment goal of a systolic blood pressure of ≤ 130 mmHg. Forty-two of a total of 100 smokers at the screening visit quit smoking within one year, resulting in a significant increase in nonsmokers at all FUVs (p < 0.0001). Recommended HbA1c levels (< 7%) were achieved in 82% without significant changes after one year. Only 7% of obese (BMI > 25) patients achieved sufficient weight reduction after one year without significant changes at all FUVs (median BMI 27 at A1; p = 0.1201). The BMT group showed significantly (p = 0.024) higher rates of adequate physical activity than the intervention groups. Furthermore, after one year, the BMT group showed a comparatively significantly better implementation of risk factor modification (77%; p = 0.027) according to the treating physician.InterpretationSPACE-2 demonstrated sustained improvement in the noninterventional management of vascular risk factors in patients treated in a clinical trial by general practitioners, internists and neurologists. The best implemented treatment targets were a reduction in cholesterol and HbA1c levels. In this context, a significant increase in statin use was demonstrated. Blood pressure control missed its target but was significantly reduced by intensification of antihypertensive medication. Patients on BMT only had better adjusted lipid parameters and were more physically active. However, all groups failed to achieve sufficient weight reduction. Due to insufficient patient recruitment, the results must be interpreted cautiously.Trial registration: ISRCTN Registry, ISRCTN78592017, Registered 16 June 2007, https://www.isrctn.com/search?q=78592017.

Elderly patients are at higher risk of procedural complications. Surgical revascularization has been performed successfully in selected octogenarians.1,2 Nevertheless, it is widely believed that percutaneous approaches are safer in the elderly. Indeed, percutaneous coronary intervention is now successfully being performed even in selected nonagenarians.3 Thus, it is tempting to presume that carotid revascularization in the elderly might be safer if done via endovascular means (Figure).4 Figure. Angiography before (A) and after (B) a right carotid artery stent in an 81-year-old man with amaurosis fugax. Article see p 2343 The data to date, however, have been conflicting, with several reports demonstrating very high rates of stroke or death with carotid stenting in octogenarians. Furthermore, although carotid stenting with embolic protection has been shown to be noninferior to carotid endarterectomy in patients at high surgical risk, whether carotid stenting is equivalent to carotid endarterectomy remains an open question in patients at low surgical risk.5–7 Additionally, especially for asymptomatic patients, the question arises whether a patient will live long enough to derive potential benefit from any procedure. This question becomes more pressing as the elderly population expands and the definition of elderly creeps upward, and also as clinical trials continue to underenroll the elderly. The cut point where appropriate clinical caution turns instead into preconceived notions and age-related bias is difficult to define. In this issue of Circulation , Chiam et al report on 142 consecutive patients aged 80 years or older who underwent carotid stenting.8 This series of patients has previously been reported, with the current article adding observations related to intermediate-term …

Near occlusion of internal carotid artery (ICA) is a rare and easily misdiagnosed condition and the decision for revascularisation still remains controversial. We conducted an updated meta-analysis in order to investigate outcomes after carotid endarterectomy (CEA), carotid artery stenting (CAS) or best medical treatment (BMT) in patients with near-occlusion of the ICA. We also aimed to investigate the role of time as a potential moderator of the near-ICA occlusion—stroke rate association. A multiple electronic health database search on articles published up to November 2019 was performed. The pooled stroke rate after CEA, CAS and BMT were calculated. We also investigated transient ischemic attack (TIA), stroke-related death, myocardial infarction (MI), any cause of death and ICA restenosis crude rates (%). A total of 33 articles were finally deemed eligible. The pooled stroke rate was 1.52% [95% confidence interval (CI): 0.09–4.02%] after CEA, 1.80% (95% CI: 0.61–3.40%) after CAS and 8.39% (95% CI: 3.39–14.80%) after BMT. Out of 896 CEA patients, we recorded 22 TIAs (2.5%), 33 all-cause deaths (3.7%), 5 stroke-related deaths (0.6%) and 6 MIs (0.7%). Concerning outcomes after 603 CAS patients, we recorded 7 TIAs (1.2%), 56 all-cause deaths (9.3%), 4 stroke-related deaths (0.7%) and 22 MIs (3.6%). Among 263 patients who were treated with BMT, we found 16 TIAs (6.1%), 10 all-cause deaths (3.8%), no stroke-related death, and no MI. Crude restenosis rate during follow-up was 9.0% (54/601) for CEA and 4.1% (24/592) for CAS patients. No significant effect of publication year upon stroke rate after CEA was recorded. However, there was a significant reversed association between pooled stroke rate after CAS and publication year (P=0.05). A statistically significant reversed association between pooled stroke rate after BMT and publication year was also recorded (P<0.01). The results of this updated meta-analysis revealed high stroke rate for patients with near-occlusion of ICA who treated only with BMT, while intervention seemed to be safe and effective. A downward trend in the stroke rates over time after CAS and BMT was also discovered. These highlight that patients with near-occlusion of ICA should be included and investigated in future studies.

Carotid stenting is a less invasive percutaneous procedure than carotid endarterectomy for the treatment of carotid stenosis. Reports suggest that it can be performed with periprocedural complication rates similar to those of carotid endarterectomy. The purpose of this study was to determine short- and long-term outcomes in the largest prospective cohort of carotid stenting patients. This study followed 528 consecutive patients (604 hemispheres/arteries) undergoing carotid stenting. There was a 0.6% (n=3) fatal stroke rate and 1% (n=5) nonstroke death rate at 30 days. The major stroke rate was 1% (n=6), and the minor stroke rate was 4.8% (n=29). The overall 30-day stroke and death rate was 7.4% (n=43). Over the 5-year study period, the 30-day minor stroke rate improved from 7.1% (n=7) for the first year to 3.1% (n=5) for the fifth year (P:<0.05 for trend). The best predictor of 30-day stroke and death was age >/=80 years. After the 30-day period, the incidence of fatal and nonfatal stroke was 3.2% (n=31). On Kaplan-Meier analysis, the 3-year freedom from ipsilateral or fatal stroke was 92+/-1%. Experience from a single group of operators demonstrates that carotid stenting can be performed with an acceptable 30-day complication rate. Late follow-up also demonstrates a low rate of fatal and nonfatal stroke. These results suggest that carotid stenting may be comparable to carotid endarterectomy, and it underscores the clinical equipoise and premise for the National Institute of Health-supported, randomized Carotid Revascularization Endarterectomy Versus Stent Trial comparing carotid stenting with carotid endarterectomy.

This commentary addresses the issue of optimal contemporary management of symptomatic and asymptomatic carotid artery stenosis. Based on current data, carotid endarterectomy (CEA) should be performed in the majority of patients with symptomatic carotid artery stenosis. Carotid artery stenting (CAS) should be reserved for a minority of these symptomatic patients, in whom CEA is contraindicated. In asymptomatic patients, all should be placed on best medical treatment (BMT). With the use of one or more of the proposed stroke risk stratification models or some as yet undetermined method, the identification of those asymptomatic individuals may be possible in whom stroke risk is higher than usual with BMT. This asymptomatic subgroup, which may be small and is yet to be determined with certainty, could be offered an invasive carotid procedure (either CAS or CEA).

Carotid Endarterectomy versus Carotid Stenting or Best Medical Treatment in Asymptomatic Patients with Significant Carotid Stenosis: A meta-analysis.

Effect of Treatment Choice on Short-Term and Long-Term Outcomes for Carotid Near-Occlusion: A Meta-Analysis

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2)