David Doig

Predictors of Stroke, Myocardial Infarction or Death within 30 Days of Carotid Artery Stenting: Results from the International Carotid Stenting Study.

Objectives Stroke, myocardial infarction (MI), and death are complications of carotid artery stenting (CAS). The effect of baseline patient demographic factors, processes of care, and technical factors during CAS on the risk of stroke, MI, or death within 30 days of CAS in the International Carotid Stenting Study (ICSS) were investigated. Methods In ICSS, suitable patients with recently symptomatic carotid stenosis > 50% were randomly allocated to CAS or endarterectomy. Factors influencing the risk of stroke, MI, or death within 30 days of CAS were examined in a regression model for the 828 patients randomized to CAS in whom the procedure was initiated. Results Of the patients, 7.4% suffered stroke, MI, or death within 30 days of CAS. Independent predictors of risk were age (risk ratio [RR] 1.17 per 5 years of age, 95% CI 1.01–1.37), a right-sided procedure (RR 0.54, 95% CI 0.32–0.91), aspirin and clopidogrel in combination prior to CAS (compared with any other antiplatelet regimen, RR 0.59, 95% CI 0.36–0.98), smoking status, and the severity of index event. In patients in whom a stent was deployed, use of an open-cell stent conferred higher risk than use of a closed-cell stent (RR 1.92, 95% CI 1.11–3.33). Cerebral protection device (CPD) use did not modify the risk. Conclusions Selection of patients for CAS should take into account symptoms, age, and side of the procedure. The results favour the use of closed-cell stents. CPDs in ICSS did not protect against stroke.

Risk Factors For Stroke, Myocardial Infarction, or Death Following Carotid Endarterectomy: Results From the International Carotid Stenting Study

Objectives Carotid endarterectomy (CEA) is standard treatment for symptomatic carotid artery stenosis but carries a risk of stroke, myocardial infarction (MI), or death. This study investigated risk factors for these procedural complications occurring within 30 days of endarterectomy in the International Carotid Stenting Study (ICSS). Methods Patients with recently symptomatic carotid stenosis >50% were randomly allocated to endarterectomy or stenting. Analysis is reported of patients in ICSS assigned to endarterectomy and limited to those in whom CEA was initiated. The occurrence of stroke, MI, or death within 30 days of the procedure was reported by investigators and adjudicated. Demographic and technical risk factors for these complications were analysed sequentially in a binomial regression analysis and subsequently in a multivariable model. Results Eight-hundred and twenty-one patients were included in the analysis. The risk of stroke, MI, or death within 30 days of CEA was 4.0%. The risk was higher in female patients (risk ratio [RR] 1.98, 95% CI 1.02–3.87, p = .05) and with increasing baseline diastolic blood pressure (dBP) (RR 1.30 per +10 mmHg, 95% CI 1.02–1.66, p = .04). Mean baseline dBP, obtained at the time of randomization in the trial, was 78 mmHg (SD 13 mmHg). In a multivariable model, only dBP remained a significant predictor. The risk was not related to the type of surgical reconstruction, anaesthetic technique, or perioperative medication regimen. Patients undergoing CEA stayed a median of 4 days before discharge, and 21.2% of events occurred on or after the day of discharge. Conclusions Increasing diastolic blood pressure was the only independent risk factor for stroke, MI, or death following CEA. Cautious attention to blood pressure control following symptoms attributable to carotid stenosis could reduce the risks associated with subsequent CEA.

Incidence, Impact, and Predictors of Cranial Nerve Palsy and Haematoma Following Carotid Endarterectomy in the International Carotid Stenting Study

Objective Cranial nerve palsy (CNP) and neck haematoma are complications of carotid endarterectomy (CEA). The effects of patient factors and surgical technique were analysed on the risk, and impact on disability, of CNP or haematoma in the surgical arm of the International Carotid Stenting Study (ICSS), a randomized controlled clinical trial of stenting versus CEA in patients with symptomatic carotid stenosis. Materials and methods A per-protocol analysis of early outcome in patients receiving CEA in ICSS is reported. Haematoma was defined by the surgeon. CNP was confirmed by an independent neurologist. Factors associated with the risk of CNP and haematoma were investigated in a binomial regression analysis. Results Of the patients undergoing CEA, 45/821 (5.5%) developed CNP, one of which was disabling (modified Rankin score = 3 at 1 month). Twenty-eight (3.4%) developed severe haematoma. Twelve patients with haematoma also had CNP, a significant association (p < .01). Independent risk factors modifying the risk of CNP were cardiac failure (risk ratio [RR] 2.66, 95% CI 1.11 to 6.40), female sex (RR 1.80, 95% CI 1.02 to 3.20), the degree of contralateral carotid stenosis, and time from randomization to treatment >14 days (RR 3.33, 95% CI 1.05 to 10.57). The risk of haematoma was increased in women, by the prescription of anticoagulant drugs pre-procedure and in patients with atrial fibrillation, and was decreased in patients in whom a shunt was used and in those with a higher baseline cholesterol level. Conclusions CNP remains relatively common after CEA, but is rarely disabling. Women should be warned about an increased risk. Attention to haemostasis might reduce the incidence of CNP. ICSS is a registered clinical trial: ISRCTN 25337470.

Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy.

Background and Purpose— Complex vascular anatomy might increase the risk of procedural stroke during carotid artery stenting (CAS). Randomized controlled trial evidence that vascular anatomy should inform the choice between CAS and carotid endarterectomy (CEA) has been lacking. Methods— One-hundred eighty-four patients with symptomatic internal carotid artery stenosis who were randomly assigned to CAS or CEA in the ICSS (International Carotid Stenting Study) underwent magnetic resonance (n=126) or computed tomographic angiography (n=58) at baseline and brain magnetic resonance imaging before and after treatment. We investigated the association between aortic arch configuration, angles of supra-aortic arteries, degree, length of stenosis, and plaque ulceration with the presence of ≥1 new ischemic brain lesion on diffusion-weighted magnetic resonance imaging (DWI+) after treatment. Results— Forty-nine of 97 patients in the CAS group (51%) and 14 of 87 in the CEA group (16%) were DWI+ (odds ratio [OR], 6.0; 95% confidence interval [CI], 2.9–12.4; P<0.001). In the CAS group, aortic arch configuration type 2/3 (OR, 2.8; 95% CI, 1.1–7.1; P=0.027) and the degree of the largest internal carotid artery angle (≥60° versus <60°; OR, 4.1; 95% CI, 1.7–10.1; P=0.002) were both associated with DWI+, also after correction for age. No predictors for DWI+ were identified in the CEA group. The DWI+ risk in CAS increased further over CEA if the largest internal carotid artery angle was ≥60° (OR, 11.8; 95% CI, 4.1–34.1) than if it was <60° (OR, 3.4; 95% CI, 1.2–9.8; interaction P=0.035). Conclusions— Complex configuration of the aortic arch and internal carotid artery tortuosity increase the risk of cerebral ischemia during CAS, but not during CEA. Vascular anatomy should be taken into account when selecting patients for stenting. Clinical Trial Registration— URL: http://www.isrctn.com/ISRCTN25337470. Unique identifier: ISRCTN25337470.

Carotid Anatomy Does Not Predict the Risk of New Ischaemic Brain Lesions on Diffusion-Weighted Imaging after Carotid Artery Stenting in the ICSS-MRI Substudy.

Introduction The International Carotid Stenting Study (ICSS, ISRCTN25337470) randomized patients with recently symptomatic carotid artery stenosis > 50% to carotid artery stenting (CAS) or endarterectomy. CAS increased the risk of new brain lesions visible on diffusion-weighted magnetic resonance imaging (DWI-MRI) more than endarterectomy in the ICSS-MRI Substudy. The predictors of new post-stenting DWI lesions were assessed in these patients. Methods ICSS-MRI Substudy patients allocated to CAS were studied. Baseline or pre-stenting catheter angiograms were rated to determine carotid anatomy. Baseline patient demographics and the influence of plaque length, plaque morphology, internal carotid angulation, and external or common carotid atheroma were examined in negative binomial regression models. Results A total of 115 patients (70% male, average age 70.4) were included; 50.4% had at least one new DWI-MRI-positive lesion following CAS. Independent risk factors increasing the number of new lesions were a left-sided stenosis (incidence risk ratio [IRR] 1.59, 95% CI 1.04–2.44, p = .03), age (IRR 2.10 per 10-year increase in age, 95% CI 1.61–2.74, p < .01), male sex (IRR 2.83, 95% CI 1.72–4.67, p < .01), hypertension (IRR 2.04, 95% CI 1.25–3.33, p < .01) and absence of cardiac failure (IRR 6.58, 95% CI 1.23–35.07, p = .03). None of the carotid anatomical features significantly influenced the number of post-procedure lesions. Conclusion Carotid anatomy seen on pre-stenting catheter angiography did not predict of the number of ischaemic brain lesions following CAS.

Carotid Stenting Versus Endarterectomy

Since the landmark NASCET and ECST trials demonstrated the superiority of carotid endarterectomy over medical therapy in the prevention of stroke for patients with symptomatic carotid artery stenosis, surgical intervention as a part of secondary prevention of stroke has become widespread. However, the newer technology of carotid artery angioplasty and stenting challenges this mode of intervention, promising the benefits of a procedure under local anesthesia and potentially avoiding the surgical complications of cranial nerve palsy and hematoma. Pooled evidence from randomized controlled trials of endarterectomy versus stenting shows a higher rate of stroke or death in the stenting groups-but this finding is mitigated to an extent by the lower incidence of myocardial infarction and cranial nerve palsy in patients undergoing stenting. At present, carotid endarterectomy combined with optimal drug therapy remains the standard of care for symptomatic 70%-99% stenosis of the internal carotid artery, but stenting might be an option in younger patients and in those not suitable for endarterectomy.

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

Summary 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.

A Painless Loss of Vision

A 49-year-old patient presents with central retinal artery occlusion. Subsequent imaging reveals thrombus in the carotid artery. Free-floating thrombus (FFT) in the common or internal carotid artery is an uncommon but important diagnosis in the patient who presents with cerebral or retinal ischaemia or infarction. FFT may be idiopathic, secondary to either an underlying arterial abnormality (carotid dissection or atherosclerotic plaque), or a procedural complication following carotid endarterectomy or stenting. The diagnosis is made through non-invasive imaging (carotid Doppler ultrasound, CT angiography or MR angiography) or at catheter angiogram. A characteristic “doughnut sign” of intraluminal filling defect surrounded by contrast is described on axial imaging. Optimal management is debated, and may differ according to aetiology. Treatment options include antithrombotic and anticoagulant drugs, carotid endarterectomy or carotid artery stenting.