International Carotid Stenting Study Research Articles

Carotid Stenting

Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year.

Periprocedural Hemodynamic Depression Is Associated With a Higher Number of New Ischemic Brain Lesions After Stenting in the International Carotid Stenting Study-MRI Substudy

Carotid artery stenting (CAS) is associated with a higher risk of both hemodynamic depression and new ischemic brain lesions on diffusion-weighted imaging than carotid endarterectomy (CEA). We assessed whether the occurrence of hemodynamic depression is associated with these lesions in patients with symptomatic carotid stenosis treated by CAS or CEA in the randomized International Carotid Stenting Study (ICSS)-MRI substudy. The number and total volume of new ischemic lesions on diffusion-weighted imaging 1 to 3 days after CAS or CEA was measured in the ICSS-MRI substudy. Hemodynamic depression was defined as periprocedural bradycardia, asystole, or hypotension requiring treatment. The number of new ischemic lesions was the primary outcome measure. We calculated risk ratios and 95% confidence intervals per treatment with Poisson regression comparing the number of lesions in patients with or without hemodynamic depression. A total of 229 patients were included (122 allocated CAS; 107 CEA). After CAS, patients with hemodynamic depression had a mean of 13 new diffusion-weighted imaging lesions, compared with a mean of 4 in those without hemodynamic depression (risk ratio, 3.36; 95% confidence interval, 1.73-6.50). The number of lesions after CEA was too small for reliable analysis. Lesion volumes did not differ between patients with or without hemodynamic depression. In patients treated by CAS, periprocedural hemodynamic depression is associated with an excess of new ischemic lesions on diffusion-weighted imaging. The findings support the hypothesis that hypoperfusion increases the susceptibility of the brain to embolism. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25337470.

Echographic Risk Index and Cerebral Ischemic Brain Lesions in Patients Randomized to Stenting versus Endarterectomy for Symptomatic Carotid Artery Stenosis

It remains to be determined whether the impact of plaque characteristics on procedural risks differs between carotid artery stenting (CAS) and endarterectomy (CEA). We studied whether quantitative assessment of carotid plaque echolucency on ultrasound predicts the risk of embolism during CAS or CEA. In 50 consecutive patients with symptomatic carotid stenosis randomized to CAS (n = 26) or CEA (n = 24) in the International Carotid Stenting Study (ICSS), semi-automated grayscale measurement of carotid plaques on baseline ultrasound was performed. We determined the grayscale median (GSM), percentage of echolucent plaque area, and a previously defined echographic risk index (ERI) calculated with the echolucent area and degree of stenosis. Brain MRI including diffusion-weighted imaging (DWI) was performed within 7 days before and 3 days after treatment. The primary outcome was the presence of at least 1 new hyperintense DWI lesion (DWI+) after treatment. In the CAS group, DWI+ patients (n = 18) had a significantly higher ERI at baseline (mean 0.11 ± 0.12) than patients without new lesions (n = 8; mean 0.03 ± 0.01; p = 0.012). GSM (mean 26.7 ± 18.7 versus 34.3 ± 8.0, p = 0.16) and echolucent plaque area (mean 42.8 ± 21.1 versus 31.2 ± 8.2, p = 0.054) did not differ significantly. In the CEA group, there were no differences in plaque echogenity measurements between patients with (n = 2) and without DWI lesions (n = 22). Patients with echolucent plaques causing severe narrowing are at increased risk for cerebral embolism during CAS. Quantitative ultrasound plaque analysis, with ERI in particular, may add to clinical variables in identifying patients at risk for procedural stroke with CAS, but larger studies with clinical endpoints are needed.

Flow Velocities in the External Carotid Artery Following Carotid Revascularization

To study the changes in peak systolic velocities of the ipsilateral external carotid artery (ECA) following carotid revascularization. All patients randomized to carotid artery stenting (CAS) or carotid endarterectomy (CEA) in the International Carotid Stenting Study (ICSS; ISRCTN25337470) in our center were included. Peak systolic velocities (PSV) were assessed with duplex ultrasound (DUS) at baseline, at 30 days, and at 12 and 24 months after treatment. Our primary outcome measure was the change in blood flow velocities in the ECA (ΔPSVECA). Secondary outcome measure was the prevalence of post interventional ECA occlusion. Of 270 patients enrolled in ICSS at our center, 224 patients (mean age, 68.8 years; 154 males) were included in the present study (116 CAS, 108 CEA). Baseline PSV in the ipsilateral ECA was similar between the groups. Following CAS, PSV gradually increased during follow-up, whereas PSV remained relatively stable after CEA; mean difference of PSV between CAS and CEA: 23 cm/s (95% CI, -5 to 52), 58 cm/s (95% CI, 27-89), and 69 cm/s (95% CI, 31-107) at 30 days, 12 months, and 24 months. One new ECA occlusion occurred after CAS and two after CEA. Blood flow velocities in the ipsilateral ECA increase significantly after CAS but not after CEA. However, this does not lead to a higher rate of ECA occlusion in the first 2 years after revascularization. We conclude that CAS is not inferior to CEA in preserving the ECA as a possible potential collateral pathway for cerebral blood supply within 2 years following revascularization.

The effect of white matter lesions on cognition after carotid revascularization

BackgroundCerebral white matter lesions (WML) are associated with cognitive impairment, and carotid revascularization with cognitive worsening or improvement. We assessed the relation between WML severity and changes in cognition after carotid endarterectomy or stenting. MethodsPatients with symptomatic carotid artery stenosis, enrolled in the International Carotid Stenting Study (ISRCTN25337470), underwent detailed neuropsychological examinations (NPEs) before and after 6months. Cognitive results were standardized into z-scores, from which a sum score was calculated. The primary outcome was the mean difference (MD) in sum score between baseline and follow-up. Changes in sum score were related to WML severity with the ‘age-related white matter changes’ score, assessed on baseline MRI-FLAIR. Three groups were formed based on this score. ResultsEighty-nine patients had both baseline MRI and NPE, of these 77 had a calculable cognitive difference score. The cognitive sum score at six months was worse than at baseline: MD, −0.21; 95% CI, −0.32 to −0.09. The change in sum score did not depend on WML load: MD for no-to-mild WML, −0.15; 95% CI, −0.39 to 0.09, for moderate WML, −0.27; 95% CI, −0.48 to −0.06; and for severe WML, −0.21; 95% CI, −0.40 to −0.04. This did not change essentially after adjustment for baseline factors. ConclusionCognitive functioning deteriorated after carotid revascularization, regardless of baseline WML burden.

Treatment of Symptomatic Carotid Stenosis: Carotid Stent Placement Versus Endarterectomy

The mainstay of treatment options for symptomatic carotid stenosis is focused around medical management, carotid endarterectomy, and carotid angioplasty and stent placement. The International Carotid Stenting Study (ICSS), also called Carotid and Vertebral Artery Transluminal Angioplasty Study 2 (CAVATAS 2), the Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy (SPACE) trial, the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, and the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) were five major trials which compared carotid endarterectomy and carotid angioplasty and stent placement. We review the results of the trials and incorporation of the results into clinical decision making.

Effects of Carotid Endarterectomy or Stenting on Arterial Diameters in the Circle of Willis

In patients with internal carotid artery (ICA) stenosis, the circle of Willis (CoW) is the primary collateral pathway. We compared luminal diameters in the CoW before and after carotid revascularization and compared the effects of carotid endarterectomy (CEA) and stenting on these diameters. At a single center in the International Carotid Stenting Study, 139 patients with symptomatic ICA stenosis of 50% or more were randomized to stenting (n = 81) or CEA (n = 58). The diameters of all segments of the CoW were assessed on computed tomography angiography (CTA), before and 30 days after revascularization. All evaluations were performed blinded to treatment allocation and order of CTA. A .10-mm increase (95% confidence interval [CI], .02-.17; 7%; P = .01) in diameter after revascularization occurred in the ipsilateral precommunicating anterior cerebral artery (A1), whereas both the ipsilateral and contralateral posterior communicating arteries decreased in diameter by .12 mm (95% CI, .04-.21; 14%; P = .01) and .08 mm (95% CI, .00-.17; 10%; P = .05), respectively. The increase in diameter of the A1 was larger after stenting (.15 mm; 95% CI, .07-.24; P = .001) than after CEA (.02 mm; 95% CI, -.11 to .15; P = .79). Only in patients treated with CEA, the diameters of the contralateral A1 and ipsilateral precommunicating posterior cerebral artery were reduced after revascularization. Carotid revascularization improves anterior collateralization and reduces reliance on posterior collateral pathways via the CoW. Carotid stenting and endarterectomy appear to have different early effects on collateralization.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial

SummaryBackgroundFindings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy.MethodsPatients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470.Findings1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17–6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10–8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40–3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38–5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29–6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45–27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7.InterpretationThe presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.

Effects of Carotid Endarterectomy or Stenting on Hemodynamic Complications in the International Carotid Stenting Study: A Randomized Comparison

Carotid endarterectomy and carotid artery stenting are frequently complicated by hemodynamic instability. The study aims to compare the incidence of hemodynamic complications between carotid artery stenting and carotid endarterectomy in the International Carotid Stenting Study (ISRCTN25337470). Patients with symptomatic carotid stenosis were randomly allocated to carotid artery stenting or carotid endarterectomy. The occurrence of peri-procedural hemodynamic depression (severe bradycardia, asystole, or hypotension requiring treatment) and hypertension requiring treatment was assessed in a per-protocol analysis. We compared the rate of hemodynamic complications, determined independent predictors thereof, and assessed their relation with the composite outcome of all-cause death, stroke, and myocardial infarction within 30 days of treatment. A number of 766 carotid artery stenting and 819 carotid endarterectomy patients had a single completed intervention. Hemodynamic depression occurred in 13.8% after carotid artery stenting and in 7.2% after carotid endarterectomy (relative risk 1.9, 95% confidence interval 1.4-2.6, P < 0.0001). Hypertension requiring treatment occurred less often after carotid artery stenting than after carotid endarterectomy (relative risk 0.2, 95% confidence interval, 0.1-0.4, P < 0.0001). In carotid artery stenting patients, a history of cardiac failure was the trongest independent predictor of hemodynamic depression (relative risk 2.4, 95% confidence interval 1.3-4.8, P = 0.009). There was no statistically significant association between hemodynamic complications and the occurrence of the composite outcome. Hemodynamic depression occurs more often after carotid artery stenting and severe hypertension more often after carotid endarterectomy, but these complications are not responsible for the excess of major perioperative events after carotid artery stenting.

Interprocedural Comparison of Changes in Natural Flow Velocity Patterns in the Internal Carotid Artery Following CAS or CEA

Different flow velocities have been reported after carotid angioplasty with stenting (CAS) than after carotid endarterectomy (CEA). We compared blood flow velocities following CAS and CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470). In total, 254 patients (70% male; 129 CAS and 125 CEA) were included. Mean peak systolic velocities (PSVICA) were assessed at baseline, 30 days, 1 and 2 years. Following both treatments, restenosis ≥ 50% was defined as PSVmean >125 cm s(-1). CAS and CEA resulted in a similar reduction in PSVICA 1 month after treatment. Post-intervention analysis for each treatment separately revealed that PSVICA following CAS increased significantly during follow-up (30 days to 2 years; 22.4 cm s(-1); 95% confidence interval (CI), 14.3 to 30.5). On the contrary, PSVICA following CEA remained relatively stable during follow-up (4.7 cm s(-1); 95% CI, -6.5 to 15.9). When we analysed the increase in PSVICA between both treatments after 2 years of follow-up, no significant interprocedural difference was observed. The internal carotid artery/common carotid artery (ICA/CCA) PSV ratio increased after CAS but not after CEA: 1.2 vs. 1.1 (0.04, 95% CI; -0.16 to 0.25) at 30 days; 1.5 vs. 1.1 (0.39, 95% CI; 0.13 to 0.65) at 1 year; and 1.5 vs. 1.1 (0.36; 95% CI, 0.08 to 0.63) at 2 years. The rate of apparent ipsilateral ICA restenosis >50% was higher following CAS (hazard ratio 2.35; 95% CI, 1.35 to 4.09). Two years after carotid revascularisation, no significant interprocedural difference was observed in the increase of PSVICA between CAS and CEA. However, the ICA/CCA ratio increased more following CAS resulting in an apparent higher rate of restenosis following CAS.

Bivalirudin for Carotid Artery Stenting

In the past decade, carotid artery stenting (CAS) has been carefully studied as a treatment for symptomatic and asymptomatic carotid artery stenosis. In the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) trial, it was shown that the composite outcome of death, stroke, or myocardial infarction is similar for CAS versus carotid endarterectomy when performed by experienced operators.1 During this time period, significant advances have been made with regards to patient selection and procedural techniques.2 In addition, there have been improvements in embolic protection and stent technology. With these advancements, CAS outcomes have continued to improve with a low rate of periprocedural adverse events observed in numerous single-center and multicenter studies.3–5 Article see p 131 In comparison with recent advances in CAS technology, intraprocedural anticoagulation during CAS has been relatively understudied. The initial randomized studies of CAS, including Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy, Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S), Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE), and the International Carotid Stenting Study (ICSS). all used heparin for adjunctive pharmacotherapy.6–9 In the CREST trial, patients randomized to CAS could be treated with either heparin (86%) or bivalirudin (14%).1 Most of the current evidence for CAS is, therefore, based on using heparin as the intraprocedural anticoagulant. The current societal guidelines for CAS do not make a specific recommendation regarding periprocedural anticoagulation but state that either heparin or bivalirudin may be used.10 A direct thrombin inhibitor, such as bivalirudin, could have significant advantages as an anticoagulant during CAS. Bivalirudin can be administered as weight-based infusion with minimal intraprocedural monitoring and predictable pharmacokinetics. In comparison, heparin has variable between-person pharmacokinetics, and the correct dose of heparin for the goal level of …

Characteristics of Ischemic Brain Lesions After Stenting or Endarterectomy for Symptomatic Carotid Artery Stenosis

In a substudy of the International Carotid Stenting Study (ICSS), more patients had new ischemic brain lesions on diffusion-weighted magnetic resonance imaging (MRI) after stenting (CAS) than after endarterectomy (CEA). In the present analysis, we compared characteristics of diffusion-weighted MRI lesions. Number, individual and total volumes, and location of new diffusion-weighted MRI lesions were compared in patients with symptomatic carotid stenosis randomized to CAS (n=124) or CEA (n=107) in the ICSS-MRI substudy. CAS patients had higher lesion numbers than CEA patients (1 lesion, 15% vs 8%; 2-5 lesions, 19% vs 5%; >5 lesions, 16% vs 4%). The overall risk ratio for the expected lesion count with CAS versus CEA was 8.8 (95% confidence interval, 4.4-17.5; P<0.0001) and significantly increased among patients with lower blood pressure at randomization, diabetes mellitus, stroke as the qualifying event, left-side stenosis, and if patients were treated at centers routinely using filter-type protection devices during CAS. Individual lesions were smaller in the CAS group than in the CEA group (P<0.0001). Total lesion volume per patient did not differ significantly. Lesions in the CAS group were more likely to occur in cortical areas and subjacent white matter supplied by leptomeningeal arteries than lesions in the CEA group (odds ratio, 4.2; 95% confidence interval, 1.7-10.2; P=0.002). Compared with patients undergoing CEA, patients treated with CAS had higher numbers of periprocedural ischemic brain lesions, and lesions were smaller and more likely to occur in cortical areas and subjacent white matter. These findings may reflect differences in underlying mechanisms of cerebral ischemia.

The risk of carotid artery stenting compared with carotid endarterectomy is greatest in patients treated within 7 days of symptoms

Among patients with symptomatic carotid artery stenosis, carotid artery stenting (CAS) is associated with a higher risk of periprocedural stroke or death than carotid endarterectomy (CEA). Uncertainty remains whether the balance of risk changes with time since the most recent ischemic event. We investigated the association of time between the qualifying ischemic event and treatment (0-7 days, 8-14 days, and >14 days) with the risk of stroke or death within 30 days after CAS or CEA in a pooled analysis of data from individual patients randomized in the Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS). Data were analyzed with a fixed-effect binomial regression model adjusted for source trial. Information on time of qualifying event was available for 2839 patients. In the first 30 days after intervention, any stroke or death occurred significantly more often in the CAS group (110/1434 [7.7%]) compared with the CEA group (54/1405 [3.8%]; crude risk ratio, 2.0; 95% confidence interval, 1.5-2.7). Patients undergoing CEA within the first 7 days of the qualifying event had the lowest periprocedural stroke or death rate (3/106 [2.8%]). Patients treated with CAS in the same period had a 9.4% risk of periprocedural stroke or death (13/138; risk ratio CAS vs CEA: 3.4; 95% confidence interval, 1.01-11.8; adjusted for age, sex, and type of qualifying event). Patients treated between 8 and 14 days showed a periprocedural stroke or death rate of 3.4% (7/208) and 8.1% (19/234), respectively, for CEA and CAS. The latest treatment group had 4% complications in the CEA group (44/1091) and 7.3% in the CAS group (78/1062). The increase in risk of CAS compared with CEA appears to be greatest in patients treated within 7 days of symptoms. Early surgery might remain most effective in stroke prevention in patients with symptomatic carotid artery stenosis.

4. Cerebral embolism in endarterectomy versus stenting for symptomatic carotid artery stenosis: The significance of plaque morphology on duplex ultrasound

Carotid stenting (CAS) and carotid endarterectomy (CEA) may be complicated by cerebral embolism which often remains clinically silent. Unstable carotid plaques might increase the risk for peri-procedural embolism. We studied whether quantitative assessment of carotid plaque echogenity on ultrasound predicts the risk of cerebral ischaemia during CAS or CEA. In 50 consecutive patients with symptomatic carotid stenosis randomised to CAS ( n = 26) or CEA ( n = 24) in the International Carotid Stenting Study, semi-automated grey scale measurement of baseline carotid ultrasound images was performed. Grey-scale median, percentage of plaque area <20th percentile of grey-scale values, and an echographic risk index based on degree of stenosis and plaque area below the 20th percentile of grey-scale values were determined, both for the entire plaque and plaque surface. Brain MRI including diffusion-weighted imaging (DWI) was performed within 7 days before and 3 days after treatment as part of the ICSS–MRI substudy. The primary outcome on MRI was the presence of at least 1 new hyperintense DWI lesion after treatment. In the CAS group, patients with new DWI lesions after treatment ( n = 18) had significantly higher whole-plaque echographic risk indices at baseline (mean 0.1050) than patients without new lesions ( n = 8; mean 0.0263; p = 0.012). GSM was 26.7 for patients with and 34.3 for patients without lesions ( p = 0.163). Other measures of plaque echogenity did not differ significantly. In the CEA group, there were no significant differences in plaque echogenity measures between patients with ( n = 2) and those without DWI lesions ( n = 23). Our results show that among patients treated with CAS, the echographic risk index was higher in patients with new ischaemic brain lesions after treatment than in those without new lesions. Quantitative ultrasound plaque analysis may be helpful in estimating the risk of embolic complications in CAS.

Treatment for routine symptomatic carotid bulb atherosclerosis

![Graphic][1] Symptomatic internal carotid artery (ICA) stenosis is a common cause of ischemic stroke. The goal of management is to decrease the risk of stroke. This objective can be reached with a combination of medical therapy and revascularization with either carotid endarterectomy (CEA) or carotid artery stenting (CAS). At this time, evidence-based medicine provides guidance for our decision regarding which revascularization procedure is the most appropriate for the patient with routine, symptomatic carotid stenosis, i.e., with no clinical or radiographic exclusions for either procedure. The choice of treatment for revascularization comes down to 3 questions: 1) If the goal is to reduce stroke, which treatment option provides the best short and long-term outcomes? 2) Which treatment is cost-effective? 3) Which treatment provides the best patient-centered outcomes? Two recent trials evaluating the difference between CEA and CAS are the Carotid Revascularization Endarterectomy vs Stent Trial (CREST)1 and the International Carotid Stenting Study (ICSS).2 In CREST, the primary composite endpoint of any stroke, myocardial infarction (MI), or death within 30 days following treatment plus any ipsilateral stroke during long-term follow-up (median 2.5 years) was similar for CAS and CEA (7.2% vs 6.8%, hazard ratio [HR] 1.1, 95% confidence interval [CI] 0.8–1.5). There was no differential treatment effect according to symptomatic status. In contrast, the ICSS interim safety analysis evaluating the 120-day rate of stroke, death, or procedural MI reported that more patients in the CAS group reached the combined endpoint of stroke, MI, or death than the CEA group (8.5% vs 5.2%, HR 1.69, 95% CI 1.16–2.45, p = 0.006).2 In addition, a subanalysis of 231 patients in ICSS underwent MRI and demonstrated more ischemic brain lesions on diffusion-weighted imaging after treatment with CAS than … [1]: /embed/inline-graphic-1.gif

Effects of Carotid Endarterectomy or Stenting on Blood Pressure in the International Carotid Stenting Study (ICSS)

Arterial hypotension is more frequently observed early after carotid artery stenting (CAS) than after carotid endarterectomy (CEA), but their long-term effects on blood pressure (BP) are unclear. We compared the effects of CAS and CEA on BP up to 1 year after treatment in the International Carotid Stenting Study. Patients with symptomatic carotid stenosis were randomly allocated to CAS or CEA. Systolic and diastolic BP were recorded at baseline, at discharge, and at 1, 6, and 12 months. Antihypertensive medication use was recorded. A per-protocol analysis was performed. Patients with missing BP records were excluded. Between-group BP changes were compared and adjusted for baseline covariates with linear regression. Within-group BP changes were compared with the paired t test. CAS (N=587) and CEA (N=637) were both associated with a decrease in BP at discharge, which was greater after CAS (mean difference in systolic BP between groups, 10.3 mm Hg; 95% CI, 7.3-13.3; P<0.0001; in diastolic BP, 4.1 mm Hg; 95% CI, 2.4-5.7; P<0.0001). During follow-up, BP changes were not different between groups. Adjustment for differences in baseline characteristics did not change the results. Fewer patients undergoing CAS used antihypertensive medication during follow-up than patients undergoing CEA (relative risk at 12 months, 0.91; 95% CI, 0.85-0.97; P=0.0073). CAS leads to a larger early decrease in BP than CEA, but this effect does not persist over time. CAS may lessen the requirement for antihypertensive medication more than CEA. Clinical Trial Registration- URL: www.controlled-trials.com. Unique identifier: ISRCTN25337470.

Response to Letter by Naggara et al Regarding Article, “Are Distal Protection Devices ‘Protective' During Carotid Angioplasty and Stenting?”

HomeStrokeVol. 42, No. 11Response to Letter by Naggara et al Regarding Article, “Are Distal Protection Devices ‘Protective' During Carotid Angioplasty and Stenting?” Free AccessReplyPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReplyPDF/EPUBResponse to Letter by Naggara et al Regarding Article, “Are Distal Protection Devices ‘Protective' During Carotid Angioplasty and Stenting?” Tiziano Tallarita, MD and Giuseppe Lanzino, MD Tiziano TallaritaTiziano Tallarita Search for more papers by this author and Giuseppe LanzinoGiuseppe Lanzino Search for more papers by this author Originally published29 Sep 2011https://doi.org/10.1161/STROKEAHA.111.629709Stroke. 2011;42:e581Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 Response:Embolic protection devices (EPD) are currently considered the standard of care during both angioplasty and stenting for carotid stenosis. However, there are limitations associated with the use of these devices, including their relative stiffness; the need for some to cross the lesion before protection is achieved; relative prolonged occlusion time for some; and the recatching phase with crossing of a freshly stented segment, with potential risk to generate distal emboli. In their systematic review of mostly single-institution observational studies, Naggara et al1 found that the pooled relative risk of stroke or death in patients treated with EPDs (EPD+) compared with those undergoing unprotected carotid artery stenting (EPD−) was 0.55 (95% CI, 0.41–0.73), and they cite methodological shortcomings in our own single-institution study.2 We routinely use protection devices during angioplasty and stenting because we believe their use makes sense despite the lack of strong evidence supporting routine use. However, we also believe there are situations where the EPD itself is the most problematic part of the procedure; in such cases, it is reasonable to perform portions of the procedure or the entire procedure without this protection. Most studies in the analysis of Naggara et al were single-institution series just like our own, with all the methodological shortcomings associated with such studies. Moreover, Naggara and colleagues ignored that most series reported in their updated systematic review (and our own is no exception) included historical EPD− controls for comparison. These patients were treated in the first phase of the learning curve for most operators, and with devices not quite as sophisticated as are ones used in more recent years. In addition, as it is common in the early phases of new technology, such as angioplasty and stenting at that time, patients considered for this treatment were true high-risk surgical candidates with significant comorbidities. This was also reflected in our series where patients treated without an EPD had significantly higher rates of hypertension, symptomatic lesions, and history of myocardial infarction, all factors shown to be associated with higher risk of periprocedural complications after angioplasty and stenting.3 The statement by Naggara et al that in our series the relative risk of stroke, myocardial infarction, or death was 0.42 in EPD+ patients is highly misleading because it does not take into account that these patients were healthier, and were treated by much more experienced operators and with much better devices than were patients who underwent EPD−.Although the evidence for EPDs comes mostly from observational, single-institution studies, there is strong evidence against them from randomized studies like in International Carotid Stenting Study (ICSS),4 and these high-quality data cannot be ignored. In conclusion, although we support the use of protection embolic devices in most cases, we do not feel that their use is absolutely necessary, and there may be situations where it is better to go unprotected; this is especially the case when placement of the protection device itself is the riskiest portion of the procedure. The main aim of our article was to trigger a healthy debate on this topic in light of ICSS data.Tiziano Tallarita, MD Division of Vascular Surgery Mayo Clinic Rochester, MNGiuseppe Lanzino, MD Department of Radiology Department of Neurosurgery Mayo Clinic Rochester, MNDisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).

Influence and Critique of CREST and ICSS Trials

The principle findings of the Carotid Revascularization Endarterectomy Versus Stenting Trial and the International Carotid Stenting Study are reviewed and discussed. Flaws and possible weaknesses in both trials are highlighted. The possibility that some Carotid Revascularization Endarterectomy Versus Stenting Trial conclusions have been misinterpreted in ways not justified by the trial's data is considered. This possibility may have prompted one conclusion of a recent American Heart Association Guideline on the management of carotid artery disease to be misleading.

Cognition after carotid endarterectomy or stenting

To compare the effect on cognition of carotid artery stenting (CAS) and carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. Patients randomized to CAS or CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470) at 2 participating centers underwent detailed neuropsychological examinations (NPE) before and 6 months after revascularization. Ischemic brain lesions were assessed with diffusion-weighted imaging before and within 3 days after revascularization. Cognitive test results were standardized into z scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up. Of the 1,713 patients included in ICSS, 177 were enrolled in the 2 centers during the substudy period, of whom 140 had an NPE at baseline and 120 at follow-up. One patient with an unreliable baseline NPE was excluded. CAS was associated with a larger decrease in cognition than CEA, but the between-group difference was not statistically significant: -0.17 (95% CI -0.38 to 0.03; p = 0.092). Eighty-nine patients had a pretreatment MRI and 64 within 3 days after revascularization. New ischemic lesions were found twice as often after CAS than after CEA (relative risk 2.1; 95% CI 1.0 to 4.4; p = 0.041). Differences between CAS and CEA in effect on cognition were not statistically significant, despite a substantially higher rate of new ischemic lesions after CAS than after CEA. This study provides Class III evidence that any difference between the effects of CAS and CEA on cognition at 6 months after revascularization is small.

Invited commentary

Invited commentary