www.dissection.co.uk, ISRNCTN44555237.

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.

SummaryBackgroundIntensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.MethodsWe did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001).InterpretationAmong patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.FundingNational Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

SummaryBackgroundThe 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).MethodsICSS 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.FindingsBetween 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.InterpretationAt 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 requir...

MRI has demonstrated the most potential, with good sensitivity and specificity for most plaque characteristics. However, currently there is no single imaging modality that can reliably identify the vulnerable plaque in relation to development of future stroke.