SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

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...

Our study showed that systemic endothelial function is not impaired in migraine patients without comorbidities, neither in those with or without aura. Considering these findings, the investigation of cerebral endothelial function would be useful in a further investigation of the role of endothelial (dys)function in migraine pathophysiology.

Background: It is well known that endothelial dysfunction plays an important role in the pathogenesis of many cardiovascular disorders. The aim of this study was to test the hypothesis that specific, marked endothelial dysfunction of cerebral arteries is present in patients with lacunar cerebral infarctions. Methods: Cerebrovascular reactivity to L-arginine, which reveals the function of the cerebral endothelium, was investigated in patients with lacunar infarctions (20 patients, 11 male and 9 female, aged 60.9 ± 7.3 years), 21 age- and gender-matched asymptomatic patients with similar cardiovascular risk factors (all patients had arterial hypertension) and 21 age- and gender-matched healthy controls. The mean arterial velocity (v_m) in both middle cerebral arteries was measured by transcranial Doppler sonography during a 15-min baseline period, a 30-min intravenous infusion of L-arginine and a 15-min interval after L-arginine infusion. Arterial blood pressure, heart rate and CO₂ were measured continuously. Results: The measured v_m increase during L-arginine infusion in the patients with lacunar infarctions (13.4 ± 9.1%) was significantly lower compared to the healthy controls (20.5 ± 9.9%) but similar to that obtained in the patients with cardiovascular risk factors (11.5 ± 8.9%). Conclusions: Our results showed that cerebrovascular reactivity to L-arginine, which demonstrates cerebral endothelial function, is significantly impaired in patients with cardiovascular risk factors. Importantly, we found that patients with lacunar infarctions do not show any additional impairment of cerebral endothelial function.

OBJECTIVE - Cerebral infarction preferentially affects the posterior cerebral artery distribution in migraine patients. The results obtained from the few known studies that have compared the anterior and posterior cerebral endothelial function are contradictory. To the best of our knowledge, cerebrovascular reactivity to L-arginine (CVR), measured by transcranial Doppler sonography (TCD), has not been previously used to determine the posterior cerebral endothelial function in migraine patients with (MwA) and without aura (MwoA). MATERIALS AND METHODS -  Forty migraine patients without comorbidities (20 MwA, 20 MwoA) and 20 healthy subjects were included. By employing strict inclusion criteria, we avoided the possible vascular risk factors. Mean arterial velocity in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was measured by TCD before and after infusion of L-arginine, and CVR to L-arginine was then calculated. RESULTS - All migraine patients had lower CVR to L-arginine in PCA (P = 0.002) and similar in MCA (P = 0.29) compared to healthy subjects. This difference was also present in MwA and MwoA compared to healthy subjects (P = 0.003). CONCLUSIONS -  Lower CVR to L-arginine in PCA in migraine patients could associate migraine and cerebral infarcts that are more common in the posterior cerebral artery distribution.