Asymptomatic Carotid Surgery Trial Research Articles

Best Medical Therapy for Asymptomatic Carotid Stenosis: Imminent or Ineffective?

Carotid artery disease accounts for approximately 20% of all ischemic strokes, a major cause of morbidity, and the fifth leading cause of death in United States. Landmark trials in the 1990s such as Asymptomatic Carotid Atherosclerosis Study (ACAS) and Asymptomatic Carotid Surgery Trial (ACST) establish carotid endarterectomy (CEA) plus best medical therapy (BMT) as the standard of care for patients with asymptomatic carotid stenosis over 60%. However, advances in medical therapy and the emergence of carotid artery stenting (CAS) have prompted a reevaluation of treatment efficacy. Recent studies have questioned the superiority of CEA over BMT alone in reducing stroke risk, suggesting no significant difference in outcomes with contemporary medical management. Additionally, analysis from the US Department of Veterans Affairs indicated minimal net benefit of CEA over BMT when accounting for all-cause mortality. Comparative studies have found no significant difference in long-term stroke free survival between CEA and CAS. However, procedural risks vary, with higher myocardial infarction rates associated with CEA and higher stroke rates with CAS. Identifying high-risk plaques and patient-specific risk factors remains crucial. Meta-analyses have highlighted features such as neovascularization and lipid rich cores as predictors of stenosis progression and ischemic events. Ongoing research, particularly the CREST-2 trial, aims to provide clear guidance on the optimal treatment of asymptomatic carotid stenosis. This trial emphasizes stringent adherence to modern BMT protocols and includes comprehensive lifestyle modification programs. The evolving landscape of medical and surgical interventions necessitates continuous evaluation to optimize treatment strategies for asymptomatic carotid stenosis, which is the impetus for this review. Future findings from ongoing trials are expected to refine current guidelines and improve patient outcomes.

William M. Feinberg Lecture: Asymptomatic Carotid Stenosis: Current and Future Considerations.

Asymptomatic high-grade carotid stenosis is an important therapeutic target for stroke prevention. For decades, the ACAS (Asymptomatic Carotid Atherosclerosis Study) and ACST (Asymptomatic Carotid Surgery Trial) trials provided most of the evidence supporting endarterectomy for patients with asymptomatic high-grade stenosis who were otherwise good candidates for surgery. Since then, transfemoral/transradial carotid stenting and transcarotid artery revascularization have emerged as alternatives to endarterectomy for revascularization. Advances in treatments against atherosclerosis have driven down the rates of stroke in patients managed without revascularization. SPACE-2 (Stent-Protected Angioplasty Versus Carotid Endarterectomy-2), a trial that included endarterectomy, stenting, and medical arms, failed to detect significant differences in stroke rates among treatment groups, but the study was stopped well short of its recruitment goal. CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) will be able to clarify whether revascularization by stenting or endarterectomy remains efficacious under conditions of intensive medical management. Transcarotid artery revascularization has a favorable periprocedural risk profile, but randomized trials comparing it to intensive medical management are lacking. Features like intraplaque hemorrhage on MRI and echolucency on B-mode ultrasonography can identify patients at higher risk of stroke with asymptomatic stenosis. High-grade stenosis with poor collaterals can cause hemispheric hypoperfusion, and unstable plaque can cause microemboli, both of which may be treatable risk factors for cognitive impairment. Evidence that there are patients with carotid stenosis who benefit cognitively from revascularization is presently lacking. New risk factors are emerging, like exposure to microplastics and nanoplastics. Strategies to limit exposure will be important without specific medical therapies.

Carotid Interventions: Does Sex Matter?

Multicentre randomised controlled trials (RCTs) consistently report that females with symptomatic and asymptomatic carotid stenoses gain less benefit following carotid interventions, compared with males. This was evident when carotid endarterectomy (CEA) was compared with best medical therapy (BMT) 1 Naylor A.R. Rothwell P.M. Bell P.R.F. Overview of the principal results and secondary analyses from the European and the North American randomised trials of carotid endarterectomy. Eur J Vasc Endovasc Surg. 2003; 26: 115-129 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ,2 Rothwell P.M. Goldstein L.B. Carotid Endarterectomy for Asymptomatic Carotid Surgery Trial. Stroke. 2004; 35: 2425-2427 Crossref PubMed Scopus (0) Google Scholar and when CEA was compared with carotid artery stenting (CAS). 3 Batchelder A. Saratzis A. Naylor A.R. Overview of primary and secondary analyses from 20 randomised controlled trials comparing carotid artery stenting with carotid endarterectomy. Eur J Vasc Endovasc Surg. 2019; 58: 479-493 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar The reduced benefit in females has been attributed to a combination of higher 30 day rates of death or stroke (vs. males) and a lower natural history risk of stroke on BMT, compared with males. These two factors have probably led to a greater proportion of females being denied carotid interventions (especially if asymptomatic). However, females are generally under represented in RCTs, and patients randomised within RCTs tend to be a highly selected subgroup of the overall population being treated, which raises questions about RCT generalisability in real world practice. Sex Related Differences in Indication and Procedural Outcomes of Carotid interventions in VASCUNETEuropean Journal of Vascular and Endovascular SurgeryPreviewIt has been suggested that peri-operative complications after carotid surgery may be higher in women than in men. This assumption may affect the treatment patterns, and it is thus possible that carotid endarterectomy (CEA) is provided to women less often. The aim of the current VASCUNET study was to determine sex related differences in operative risk in routine clinical practice among non-selected patients undergoing carotid revascularisation. Full-Text PDF Open Access

Treatment of asymptomatic carotid artery stenosis

There is much debate about the best approach for treating patients with tight (at least 70%) asymptomatic carotid artery stenosis. A pooled analysis of trials in recently symptomatic patients with carotid artery stenosis showed that successful, uncomplicated surgery or stenting had similar long-term outcomes for at least 8 years, but early post-procedural strokes were more common after stenting than surgery. 1 Brott TG Calvet D Howard G et al. Long-term outcomes of stenting and endarterectomy for symptomatic carotid stenosis: a preplanned pooled analysis of individual patient data. Lancet Neurol. 2019; 18: 348-356 Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar The ACST-2 trial reported that, for asymptomatic patients, both procedures had similar procedural and 5-year follow-up outcomes. 2 Halliday A Bulbulia R Bonati LH et al. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy. Lancet. 2021; 398: 1065-1073 Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar However, medical treatment for asymptomatic carotid artery stenosis has improved substantially in the past 20 years, when many clinical trials in this population were done, and best medical treatment could now be an option instead of more invasive approaches. 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 trialCEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. Full-Text PDF

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

SummaryBackgroundAmong asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.MethodsACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.FindingsBetween Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21).InterpretationSerious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable.FundingUK Medical Research Council and Health Technology Assessment Programme.

Stroke Prevention and Dementia: 15-year Follow-up of the Asymptomatic Carotid Surgery Trial-1 (ACST-1)

Stroke Prevention and Dementia: 15-year Follow-up of the Asymptomatic Carotid Surgery Trial-1 (ACST-1)

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 …

The Asymptomatic Carotid Surgery Trial-2 (ACST-2): an ongoing randomised controlled trial comparing carotid endarterectomy with carotid artery stenting to prevent stroke.

A successful open surgical operation to remove atheromatous carotid artery narrowing that has not yet caused a stroke (asymptomatic carotid stenosis) carries some procedural risk but, if completed successfully, halves patients' future annual stroke risk for at least 10 years. A newer, less invasive alternative is carotid stenting, which also carries some procedural risk, especially if the carotid lesion has recently given rise to a stroke (symptomatic carotid stenosis). For both surgery and stenting, improvements in technique (and in medication) have reduced risk. Early studies showed that treating carotid narrowing by stenting, particularly for symptomatic lesions, caused more procedural minor strokes than surgery, but more recent trials in symptomatic and in asymptomatic patients found that both procedures might now be equally safe and effective. However, low patient numbers, short follow-up of the long-term effects on stroke rates and wide confidence intervals mean that worldwide uncertainty persists between carotid surgery and carotid stenting, and national and international guidelines remain unclear as to which is generally better. The second Asymptomatic Carotid Surgery Trial (ACST-2) compares carotid endarterectomy (CEA) with carotid artery stenting (CAS) directly, randomising patients with asymptomatic carotid stenosis for whom a carotid procedure is considered definitely necessary; both procedures seem anatomically feasible, and there is substantial uncertainty as to which of the two would be better for such individuals. Although it will compare procedural risks, the trial's primary aim is to compare the long-term durability of protection against strokes occurring in the years post procedure due to any remaining or recurrent carotid disease. Randomised controlled trial comparing CEA with CAS. Hospitals in the UK and worldwide, in which carotid procedures are common. Men and women with severely stenotic atherosclerotic carotid artery disease, with or without previous stroke but with no recent symptoms from the randomised artery. CEA and CAS. (1) Periprocedural risk defined as myocardial infarction, stroke or death within 30 days after the randomised procedure and (2) long-term rates of disabling or fatal stroke during follow-up of patients. Measurement of intervention costs and stroke costs (periprocedural and during follow-up) and of quality of life [EuroQol-5 Dimensions (EQ-5D®)] for patients in the top six recruiting countries (UK, Italy, Belgium, Germany, Serbia and Sweden), who currently constitute 85% of those randomised. By the end of March 2016, ACST-2 had included 2125 patients, nearly two-thirds of the planned recruitment of 3600; 1061 were randomly allocated to CEA and 1064 to CAS. Further funding has been secured and recruitment continues, with completion anticipated by the end of 2019. ACST-2 will report initial results in 2021. Current Controlled Trials ISRCTN21144362. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 57. See the NIHR Journals Library website for further project information. Funding was also received from BUPA Foundation [BUPAF/33(a)/05].

Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study

Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90-99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90-99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p<.001), but this choice did not appear to be dependent on patient characteristics. In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

Evidence-Based Carotid Interventions for Stroke Prevention: State-of-the-art Review.

Carotid artery stenosis is responsible for between 10–20% of all ischaemic strokes. Interventions, such as carotid end-arterectomy and carotid stenting, effectively reduce the risk of stroke in selected individuals. This review describes the history of carotid interventions, and summarises reliable evidence on the safety and efficacy of these interventions gained from large randomised clinical trials.Early trials comparing carotid endarterectomy to medical therapy alone in symptomatic patients, and asymptomatic patients, demonstrated that endarterectomy halved the risk of stroke and perioperative death in these two unique populations. The absolute risk reduction was smaller in the asymptomatic carotid trials, consistent with their lower absolute stroke risk. More recent trials in symptomatic patients, suggest that carotid stenting has similar long term durability to carotid endarterectomy, but possibly has higher procedural hazards dominated by non-disabling strokes. The Asymptomatic Carotid Surgery Trial-2, along with individual patient data meta-analysis of all asymptomatic trials, will provide reliable evidence for the choice of intervention in asymptomatic patients in whom a decision has been made for carotid revascularisation. Given improvements in effective cardiovascular medical therapy, in particular lipid-lowering medications, there is renewed uncertainty as to whether carotid interventions still provide meaningful net reductions in stroke risk in asymptomatic populations. Four large trials in Europe and the US are currently underway, and are expected to report longterm results in the next decade.It is essential that surgeons, interventionalists, and physicians continue to randomise large numbers of patients from around the world to clarify current uncertainty around the management of asymptomatic carotid stenosis.

Ten-year risk of stroke in patients with previous cerebral infarction and the impact of carotid surgery in the Asymptomatic Carotid Surgery Trial.

Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy. The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack > 6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups. Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p = 0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p = 0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio = 1.51, 95% confidence interval: 1.17-1.95, p = 0.002) and of stroke or other vascular death (hazard ratio = 1.30, 95% confidence interval: 1.11-1.52, p = 0.001). At 10 years, greater absolute benefits from immediate carotid endarterectomy were seen in those patients with prior cerebral infarction (6.7% strokes immediate carotid endarterectomy vs. 14.7% delayed carotid endarterectomy; hazard ratio 0.47 (0.34-0.65), p = 0.003), compared to those lower risk patients without prior cerebral infarction (6.0% vs. 9.9%, respectively; hazard ratio 0.61 (0.39-0.94), p = 0.005), though it must be emphasized that the first Asymptomatic Carotid Surgery Trial was not designed to test this retrospective and non-randomized comparison. Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial.

Clinical Experience amongst Surgeons in the Asymptomatic Carotid Surgery Trial-1

Introduction: Hospital volume may influence the outcomes of carotid revascularization, but in trials the effect of the clinical experience of individual surgeons on procedural outcome is less certain. We assessed perioperative event rates amongst centers with different trial entry volumes and also the effects of individual operator experience in the first Asymptomatic Carotid Surgery Trial-1 (ACST-1). Methods: In 126 centers participating in ACST-1, surgeons were classified according to their in-trial experience (group A: 50 cases; group B: 51-100 cases; group C: >100 cases), center enrolment volume (group I: <30 patients; group II: 30-75 patients; group III: >75 patients) and center annual hospital volume (group 1: <40 carotid endarterectomies (CEAs); group 2: 40-75 CEAs; group 3: >75 cases). Differences in perioperative event rates were compared using logistic regression analysis. Results: In centers with the most clinical experience compared with those with least experience (groups C vs. A), the number of strokes or deaths was 8 of 275 (2.9%) versus 24 of 810 (3.0%) with OR 0.99 (95% CI 0.44-2.25, p = 0.986). Numbers of strokes or death in high enrolment centers compared with those in low enrolment centers (groups III vs. I) was 20 of 680 (2.9%) versus 21 of 580 (3.6%) with OR 0.81 (95% CI 0.43-1.51, p = 0.921). In centers with a high annual volume compared with those of low annual volume (groups 3 vs. 1), numbers of strokes and death were non-significantly lower, 26 of 823 (3.2%) versus 19 of 422 (4.5%) with OR 0.68 (95% CI 0.37-1.26, p = 0.386). Cumulative stroke risk at 5 and 10 years were similar among different levels of reported clinical experience, enrolment volume and annual hospital volume. Conclusion: Although our data did not demonstrate an association between perioperative complications and operators' experience, enrolment volume or annual hospital volume, rates of stroke or death were numerically lower in both high enrolment and high annual volume centers. This lack of association could be explained by an overall low procedural risk in ACST-1.

The Mechanism of Procedural Stroke Following Carotid Endarterectomy within the Asymptomatic Carotid Surgery Trial 1

Introduction: Understanding the pathophysiological mechanism of procedural stroke during carotid intervention may help reduce the risk of stroke in those undergoing surgery. We therefore studied the features of procedural strokes within the first Asymptomatic Carotid Surgery Trial-1 (ACST-1) to identify the underlying pathophysiological mechanism. Methods: In ACST-1, 3,120 patients with severe asymptomatic carotid stenosis thought suitable for surgery were randomized to CEA or indefinite deferral of surgery. Information on procedural (within 30 days) stroke type, laterality, severity and timing was collected. Eight possible mechanisms were defined: embolism from the carotid artery, haemodynamic, thrombosis or occlusion of the carotid artery, hyperperfusion syndrome, cardioembolic, either carotid embolic or haemodynamic, either carotid embolic or thrombotic occlusion, or undetermined. Results: Procedural strokes occurred in 53 patients (2.7%). Strokes were predominantly ischaemic (n = 43; 81%), ipsilateral to the treated artery (n = 42; 79%), often occurred on the day of the operation (n = 32; 60%) and in over half the patients, were disabling or fatal (n = 27; 51%). The identified stroke mechanism was carotid embolic (n = 7), haemodynamic (n = 5), thrombosis or occlusion of the carotid artery (n = 9), hyperperfusion (n = 7), cardioembolic (n = 3), ‘probably carotid embolic or haemodynamic' (n = 7), ‘probably carotid embolic or thrombotic occlusion' (n = 3) and undetermined in 12 cases. Conclusion: In ACST-1, the risk of procedural stroke was low. Most strokes (60%) occurred on the day of the procedure and were caused by thrombosis or thrombotic occlusion of the ipsilateral carotid artery. These findings emphasize the importance of immediate assessment of the treated carotid artery when a stroke occurs after CEA.

Commentary on ‘Plaque Echolucency and the Risk of Ischaemic Stroke in Patients with Asymptomatic Carotid Stenosis Within the First Asymptomatic Carotid Surgery Trial (ACST-1)’

Objective/Background: On ultrasound, potentially “high risk” carotid plaques may appear echolucent. In this study, whether a confident classification of echolucent plaque was a predictor of future ipsilateral ischaemic stroke in asymptomatic patients randomized to medical therapy in the Asymptomatic Carotid Surgery Trial-1 (ACST-1) was assessed. Methods: We performed a post-hoc analysis of 814 ACST-1 patients randomized to medical therapy alone with baseline plaque assessment classified as definitely echolucent (> 25% soft plaque) or nonecholucent ( 25% soft plaque) was associated with a higher 5-year ipsilateral stroke risk in ACST-1 and may therefore help to identify

Plaque Echolucency and the Risk of Ischaemic Stroke in Patients with Asymptomatic Carotid Stenosis Within the First Asymptomatic Carotid Surgery Trial (ACST-1)

On ultrasound, potentially "high risk" carotid plaques may appear echolucent. In this study, whether a confident classification of echolucent plaque was a predictor of future ipsilateral ischaemic stroke in asymptomatic patients randomized to medical therapy in the Asymptomatic Carotid Surgery Trial-1 (ACST-1) was assessed. We performed a post-hoc analysis of 814 ACST-1 patients randomized to medical therapy alone with baseline plaque assessment classified as definitely echolucent (> 25% soft plaque) or nonecholucent (< 25% soft plaque). Kaplan-Meier survival curves were used to compare cumulative rates of ipsilateral ischaemic stroke in both groups. In the first 5 years after randomization, a significantly higher risk of ipsilateral stroke was observed in patients with definitely echolucent plaques (8.0%; 95% confidence interval [CI] 6.4-9.6) when compared with patients with definitely nonecholucent plaques (3.1%; 95% CI 2.1-4.1; p=.009). After adjustments for other risk factors, plaque echolucency was associated with a 2.5-times increased risk of ipsilateral ischaemic stroke (hazard ratio 2.52; 95% CI 1.20-5.25; p=.014). Use of lipid-lowering therapy was low in both groups during the first 5 years after randomization but rose sharply during years 5-10 of follow-up, and was significantly more likely to be prescribed for patients with echolucent plaques (p=.001). The risk of ipsilateral ischaemic stroke at 10 years was similar for both groups of patients (p=.233). Although the numbers of events in this study was low, definite plaque echolucency (> 25% soft plaque) was associated with a higher 5-year ipsilateral stroke risk in ACST-1 and may therefore help to identify patients at increased risk of stroke for whom carotid intervention may be particularly beneficial.

Antiplatelet Therapy in Carotid Artery Stenting and Carotid Endarterectomy in the Asymptomatic Carotid Surgery Trial-2

Strokes are infrequent but potentially serious complications following carotid intervention, but antiplatelet therapy can reduce these risks. There are currently no specific guidelines on dose or duration of peri-procedural antiplatelet treatment for patients undergoing carotid intervention. Within the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), this study aimed at assessing the current use of antiplatelet therapy before, during, and after CEA and CAS in patients with asymptomatic carotid stenosis. Questionnaires were sent to ACST-2 collaborators seeking information about the use of antiplatelet therapy during the pre-, peri-, and post-operative periods in patients undergoing carotid intervention at 77 participating sites and also whether sites tested for antiplatelet therapy resistance. The response rate was 68/77 (88%). For CAS, 82% of sites used dual antiplatelet therapy (DAPT) pre-operatively and 86% post-operatively with a mean post-procedural duration of 3 months (range 1-12), while 9% continued DAPT life-long. For CEA only 31% used DAPT pre-operatively, 24% post-operatively with a mean post-procedural duration of 3 months (range 1-5), while 10% continued DAPT life-long. For those prescribing post-procedural mono antiplatelet (MAPT) therapy (76%), aspirin was more commonly prescribed (59%) than clopidogrel (6%) and 11% of centres did not show a preference for either aspirin or clopidogrel. Eleven centres (16%) tested for antiplatelet therapy resistance. There appears to be broad agreement on the use of antiplatelet therapy in ACST-2 patients undergoing carotid artery stenting and surgery. Although evidence to help guide the duration of peri-procedural antiplatelet therapy is limited, long-term treatment with DAPT appears similar between both treatment arms.

Definite Plaque Echolucency is Associated with a Higher Risk of Ipsilateral Ischaemic Stroke during Early Follow up in the Asymptomatic Carotid Surgery Trial-1 (ACST-1)

Definite Plaque Echolucency is Associated with a Higher Risk of Ipsilateral Ischaemic Stroke during Early Follow up in the Asymptomatic Carotid Surgery Trial-1 (ACST-1)

Progression Rate and Ipsilateral Neurological Events in Asymptomatic Carotid Stenosis

Background and Purpose—Progression of asymptomatic carotid stenoses with >50% luminal narrowing is associated with an increased risk of stroke. The significance of the progression rate in these patients is unknown. The main aim of this study was to evaluate the rate of change of carotid luminal narrowing over 1 year, as a risk factor for ipsilateral ischemic events, in patients with a >50% asymptomatic carotid stenosis. Secondary aims were to establish the incidence of changes in carotid luminal narrowing and establish additional risk factors for ipsilateral neurological events. Methods—A retrospective analysis was conducted of data derived from the deferred endarterectomy arm of the Asymptomatic Carotid Surgery Trial. Patients were followed up for ≥5 years with serial carotid duplex examinations. Data were derived from information obtained at randomization and annual follow-up visits with carotid duplex examination. Potential risk factors for ipsilateral neurological events were analyzed in Poisson regre...

Plaque Morphology and Embolic Protection Strategies in Carotid Artery Stenting

ach year, approximately 800,000 strokes occur in the United States, 80% of which are ischemic. Of that 80%, E 15%e20% are caused by extracranial carotid artery disease (3). The risk of stroke due to both symptomatic and asymptomatic carotid stenosis, as well as the benefit of repair by carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS), has been well documented in clinical trials. Both the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) demonstrated a significant benefit to CEA for those with severe (70%e80%) symptomatic stenosis. In NASCET, the risk of stroke with medical therapy was 26% over 2 years compared to 9% with CEA (16). The ECST documented stroke risks over 3 years formedical therapy andCEA to be 26.5% and 14.9%, respectively (6, 7). CEA has also been shown to be of benefit in those with asymptomatic disease, although the effect was not as profound. The Asymptomatic Carotid Atherosclerosis Study (ACAS) reported an 11% risk of stroke over 5 yearswithmedical therapy versus 5.1%with CEA for those with greater than 60% stenosis (8), and the Asymptomatic Carotid Surgery Trial (ACST) demonstrated an 11.8% risk with medical

Risk of Stroke From New Carotid Artery Occlusion in the Asymptomatic Carotid Surgery Trial-1

During long-term follow-up of patients with asymptomatic carotid stenosis, occlusion and stroke were more common among patients with ≥70% stenosis. Occlusion is an independent prognostic risk factor for stroke.