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Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): secondary analysis of a randomised trial.

ABSTRACT:

Background

The risk of stroke associated with carotid artery restenosis after stenting or endarterectomy is unclear. We aimed to compare the long-term risk of restenosis after these treatments and to investigate if restenosis causes stroke in a secondary analysis of the International Carotid Stenting Study (ICSS).

Methods

ICSS is a parallel-group randomised trial at 50 tertiary care centres in Europe, Australia, New Zealand, and Canada. Patients aged 40 years or older with symptomatic carotid stenosis measuring 50% or more were randomly assigned either stenting or endarterectomy in a 1:1 ratio. Randomisation was computer-generated and done centrally, with allocation by telephone or fax, stratified by centre, and with minimisation for sex, age, side of stenosis, and occlusion of the contralateral carotid artery. Patients were followed up both clinically and with carotid duplex ultrasound at baseline, 30 days after treatment, 6 months after randomisation, then annually for up to 10 years. We included patients whose assigned treatment was completed and who had at least one ultrasound examination after treatment. Restenosis was defined as any narrowing of the treated artery measuring 50% or more (at least moderate) or 70% or more (severe), or occlusion of the artery. The degree of restenosis based on ultrasound velocities and clinical outcome events were adjudicated centrally; assessors were masked to treatment assignment. Restenosis was analysed using interval-censored models and its association with later ipsilateral stroke using Cox regression. This trial is registered with the ISRCTN registry, number ISRCTN25337470. This report presents a secondary analysis, and follow-up is complete.

Findings

Between May, 2001, and October, 2008, 1713 patients were enrolled and randomly allocated treatment (855 were assigned stenting and 858 endarterectomy), of whom 1530 individuals were followed up with ultrasound (737 assigned stenting and 793 endarterectomy) for a median of 4·0 years (IQR 2·3-5·0). At least moderate restenosis (≥50%) occurred in 274 patients after stenting (cumulative 5-year risk 40·7%) and in 217 after endarterectomy (29·6%; unadjusted hazard ratio [HR] 1·43, 95% CI 1·21-1·72; p<0·0001). Patients with at least moderate restenosis (≥50%) had a higher risk of ipsilateral stroke than did individuals without restenosis in the overall patient population (HR 3·18, 95% CI 1·52-6·67; p=0·002) and in the endarterectomy group alone (5·75, 1·80-18·33; p=0·003), but no significant increase in stroke risk after restenosis was recorded in the stenting group (2·03, 0·77-5·37; p=0·154; p=0·10 for interaction with treatment). No difference was noted in the risk of severe restenosis (≥70%) or subsequent stroke between the two treatment groups.

Interpretation

At least moderate (≥50%) restenosis occurred more frequently after stenting than after endarterectomy and increased the risk for ipsilateral stroke in the overall population. Whether the restenosis-mediated risk of stroke differs between stenting and endarterectomy requires further research.

Funding

Medical Research Council, the Stroke Association, Sanofi-Synthélabo, and the European Union.

SUBMITTER: Bonati LH

PROVIDER: S-EPMC6004555 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments.MethodsPatients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470.Findings1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups.InterpretationLong-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis.FundingMedical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Project description:ObjectiveTo decrease the procedural risk of carotid revascularisation it is crucial to understand the mechanisms of procedural stroke. This study analysed the features of procedural strokes associated with carotid artery stenting (CAS) and carotid endarterectomy (CEA) within the International Carotid Stenting Study (ICSS) to identify the underlying pathophysiological mechanism.Materials and methodsPatients with recently symptomatic carotid stenosis (1,713) were randomly allocated to CAS or CEA. Procedural strokes were classified by type (ischaemic or haemorrhagic), time of onset (intraprocedural or after the procedure), side (ipsilateral or contralateral), severity (disabling or non-disabling), and patency of the treated artery. Only patients in whom the allocated treatment was initiated were included. The most likely pathophysiological mechanism was determined using the following classification system: (1) carotid-embolic, (2) haemodynamic, (3) thrombosis or occlusion of the revascularised carotid artery, (4) hyperperfusion, (5) cardio-embolic, (6) multiple, and (7) undetermined.ResultsProcedural stroke occurred within 30 days of revascularisation in 85 patients (CAS 58 out of 791 and CEA 27 out of 819). Strokes were predominately ischaemic (77; 56 CAS and 21 CEA), after the procedure (57; 37 CAS and 20 CEA), ipsilateral to the treated artery (77; 52 CAS and 25 CEA), and non-disabling (47; 36 CAS and 11 CEA). Mechanisms of stroke were carotid-embolic (14; 10 CAS and 4 CEA), haemodynamic (20; 15 CAS and 5 CEA), thrombosis or occlusion of the carotid artery (15; 11 CAS and 4 CEA), hyperperfusion (9; 3 CAS and 6 CEA), cardio-embolic (5; 2 CAS and 3 CEA) and multiple causes (3; 3 CAS). In 19 patients (14 CAS and 5 CEA) the cause of stroke remained undetermined.ConclusionAlthough the mechanism of procedural stroke in both CAS and CEA is diverse, haemodynamic disturbance is an important mechanism. Careful attention to blood pressure control could lower the incidence of procedural stroke.

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Project description:BACKGROUND:Over the past decades, stroke risk associated with carotid disease has decreased, reflecting improvements in medical therapy and a more rigorous control of vascular risk factors. It is less clear whether the procedural risk of carotid revascularization has declined over time. METHODS:We analyzed temporal changes in procedural risks among 4597 patients with symptomatic carotid stenosis treated with carotid artery stenting (n=2326) or carotid endarterectomy (n=2271) in 4 randomized trials between 2000 and 2008, using generalized linear mixed-effects models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, occurring during or within 30 days after revascularization. RESULTS:The procedural stroke or death risk decreased significantly over time in all patients (unadjusted odds ratio per year, 0.91; 95% CI, 0.85-0.97; P=0.006). This effect was driven by a decrease in the carotid endarterectomy group (unadjusted odds ratio per year, 0.82; 95% CI, 0.73-0.92; P=0.003), whereas no significant decrease was found after carotid artery stenting (unadjusted odds ratio, 0.96; 95% CI, 0.88-1.04; P=0.33). Carotid endarterectomy patients had a lower procedural stroke or death risk compared with carotid artery stenting patients, and the difference significantly increased over time (interaction P=0.031). After adjustment for baseline characteristics, the results remained essentially the same. CONCLUSIONS:The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over an 8-year period, independent of clinical predictors of procedural risk. No corresponding reduction in procedural risk was seen in patients treated with stenting. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov; http://www.isrctn.com. Unique identifier: NCT00190398 (EVA-3S), NCT00004732 (CREST), ISRCTN57874028 (SPACE), and ISRCTN25337470 (ICSS).

Project description:PurposeWe aimed to evaluate the long-term outcome of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in patients who underwent both procedures on different sides.MethodsIn this single-center retrospective study (2001-2019), 117 patients (men, N = 78; median age at CEA, 64.4 [interquartile range {IQR}, 57.8-72.2] years; median age at CAS, 68.8 [IQR, 61.0-76.0] years) with ≥50% internal carotid artery stenosis who had CEA on one side and CAS on the other side were included. The risk of restenosis was estimated by treatment adjusted for patient and lesion characteristics.ResultsNeurological symptoms were significantly more common (41.9% vs 16.2%, P<0.001) and patients had a significantly shorter mean duration of smoking (30.2 [standard deviation {SD}, 22.2] years vs 31.8 [SD, 23.4] years, P<0.001), hypertension (10.1 [SD, 9.8] years vs 13.4 [SD, 9.1] years, P<0.001), hyperlipidemia (3.6 [SD, 6.6] years vs 5.0 [SD, 7.3] years, P = 0.001), and diabetes mellitus (3.9 [SD, 6.9] years vs 5.7 [SD, 8.9] years, P<0.001) before CEA compared to those before CAS. While the prevalence of heavily calcified stenoses on the operated side (25.6% vs 6.8%, P<0.001), the incidence of predominantly echogenic/echogenic plaques (53.0% vs 70.1%, P = 0.011) and suprabulbar lesions (1.7% vs 22.2%, P<0.001) on the stented side was significantly higher. Restenosis rates were 10.4% at 1 year, 22.3% at 5 years, and 33.7% at the end of the follow-up (at 11 years) for CEA, while these were 11.4%, 14.7%, and 17.2%, respectively, for CAS. Cox regression analysis revealed a significantly higher risk of restenosis (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.05-3.10; P = 0.030) for CEA compared to that for CAS. After adjusting for relevant confounding factors (smoking, hypertension, diabetes mellitus, calcification severity, plaque echogenicity, and lesion location), the estimate effect size materially did not change, although it did not remain statistically significant (HR, 1.85; 95% CI, 0.95-3.60; P = 0.070).ConclusionIntra-patient comparison of CEA and CAS in terms of restenosis tilts the balance toward CAS.

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Project description:BackgroundIn the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion.MethodsPatients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732.Findings2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42).InterpretationRestenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation.FundingNational Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

Project description:BackgroundCarotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke.MethodsWe randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization.ResultsFor 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85).ConclusionsAmong patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)