Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting).

BACKGROUND: Temporary interruption of cerebral blood flow during carotid endarterectomy can be avoided by using a shunt across the clamped section of the carotid artery. The shunt may improve the outcome. This is an update of a Cochrane review originally published in 1996 and previously updated in 2002, 2009, and 2014. OBJECTIVES: To assess the effect of routine versus selective or no shunting, and to assess the best method for selective shunting on death, stroke, and other complications in people undergoing carotid endarterectomy under general anaesthesia. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched April 2021), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2021, Issue 4), MEDLINE (1966 to April 2021), Embase (1980 to April 2021), and the Science Citation Index Expanded (SCI-EXPANDED) (1980 to April 2021). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform, and handsearched relevant journals, conference proceedings, and reference lists. SELECTION CRITERIA: Randomised and quasi-randomised trials of routine shunting compared with no shunting or selective shunting, and trials that compared different shunting policies in people undergoing carotid endarterectomy. DATA COLLECTION AND ANALYSIS: Three independent review authors performed data extraction, selection, and analysis. A pooled Peto odds ratio (OR) and 95% confidence interval (CI) were computed for all outcomes of interest. Best and worse case scenarios were also calculated in case of unavailable data. Two authors independently assessed risk of bias, and quality of evidence using GRADE. MAIN RESULTS: No new trials were found for this updated review. Thus, six trials involving 1270 participants are included in this latest review: three trials involving 686 participants compared routine shunting with no shunting, one trial involving 200 participants compared routine shunting with selective shunting, one trial involving 253 participants compared selective shunting with and without near-infrared refractory spectroscopy monitoring, and the other trial involving 131 participants compared shunting with a combination of electroencephalographic and carotid pressure measurement with shunting by carotid pressure measurement alone. Only three trials comparing routine shunting and no shunting were eligible for meta-analysis. Major findings of this comparison found that the routine shunting had less risk of stroke-related death within 30 days of surgery (best case) than no shunting (Peto odds ratio (OR) 0.13, 95% confidence interval (CI) 0.02 to 0.96, I2 not applicable, P = 0.05, low-quality evidence), the routine shunting group had a lower stroke rate within 24 hours of surgery (Peto odds ratio (OR) 0.15, 95% CI 0.03 to 0.78, I2 = not applicable, P = 0.02, low-quality evidence), and ipsilateral stroke within 30 days of surgery (best case) (Peto OR 0.41, 95% CI 0.18 to 0.97, I2 = 52%, P = 0.04, low-quality evidence) than the no shunting group. No difference was found between the groups in terms of postoperative neurological deficit between selective shunting with and without near-infrared refractory spectroscopy monitoring. However, this analysis was inadequately powered to reliably detect the effect. There was no difference between the risk of ipsilateral stroke in participants selected for shunting with the combination of electroencephalographic and carotid pressure assessment compared with pressure assessment alone, although again the data were limited. AUTHORS' CONCLUSIONS: This review concluded that the data available were too limited to either support or refute the use of routine or selective shunting in carotid endarterectomy when performed under general anaesthesia. Large-scale randomised trials of routine shunting versus selective shunting are required. No method of monitoring in selective shunting has been shown to produce better outcomes.

Local versus general anaesthesia for carotid endarterectomy.

BACKGROUND: Carotid endarterectomy may significantly reduce the risk of stroke in people with recently symptomatic, severe carotid artery stenosis. However, there are significant perioperative risks that may be minimised by performing the operation under local rather than general anaesthetics. This is an update of a Cochrane Review first published in 1996, and previously updated in 2004, 2008, and 2013. OBJECTIVES: To determine whether carotid endarterectomy under local anaesthetic: 1) reduces the risk of perioperative stroke and death compared with general anaesthetic; 2) reduces the complication rate (other than stroke) following carotid endarterectomy; and 3) is acceptable to individuals and surgeons. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers (to February 2021). We also reviewed reference lists of articles identified. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of local anaesthetics to general anaesthetics for people having carotid endarterectomy were eligible. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, assessed risk of bias, and evaluated quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. We calculated a pooled Peto odds ratio (OR) and corresponding 95% confidence interval (CI) for the following outcomes that occurred within 30 days of surgery: stroke, death, ipsilateral stroke, stroke or death, myocardial infarction, local haemorrhage, and arteries shunted. MAIN RESULTS: We included 16 RCTs involving 4839 participants, of which 3526 were obtained from the single largest trial (GALA). The main findings from our meta-analysis showed that, within 30 days of operation, neither incidence of stroke nor death were significantly different between local and general anaesthesia. Of these, the incidence of stroke in the local and general anaesthesia groups was 3.2% and 3.5%, respectively (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.66 to 1.26; P = 0.58; 13 studies, 4663 participants; low-quality evidence). The rate of ipsilateral stroke under both types of anaesthesia was 3.1% (Peto OR 1.03, 95% CI 0.71 to 1.48; P = 0.89; 2 studies, 3733 participants; low-quality evidence). The incidence of stroke or death in the local anaesthesia group was 3.5%, while stroke or death incidence was 4.1% in the general anaesthesia group (Peto OR 0.85, 95% CI 0.62 to 1.16; P = 0.31; 11 studies, 4391 participants; low-quality evidence). A lower rate of death was observed in the local anaesthetic group but evidence was of low quality (Peto OR 0.61, 95% CI 0.35 to 1.06; P = 0.08; 12 studies, 4421 participants). AUTHORS' CONCLUSIONS: The incidence of stroke and death were not convincingly different between local and general anaesthesia for people undergoing carotid endarterectomy. The current evidence supports the choice of either approach. Further high-quality studies are still needed as the evidence is of limited reliability.

Patches of different types for carotid patch angioplasty.

BACKGROUND: Extracranial carotid artery stenosis is the major cause of stroke, which can lead to disability and mortality. Carotid endarterectomy (CEA) with carotid patch angioplasty is the most popular technique for reducing the risk of stroke. Patch material may be made from an autologous vein, bovine pericardium, or synthetic material including polytetrafluoroethylene (PTFE), Dacron, polyurethane, and polyester. This is an update of a review that was first published in 1996 and was last updated in 2010. OBJECTIVES: To assess the safety and efficacy of different types of patch materials used in carotid patch angioplasty. The primary hypothesis was that a synthetic material was associated with lower risk of patch rupture versus venous patches, but that venous patches were associated with lower risk of perioperative stroke and early or late infection, or both. SEARCH METHODS: We searched the Cochrane Stroke Group trials register (last searched 25 May 2020); the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4), in the Cochrane Library; MEDLINE (1966 to 25 May 2020); Embase (1980 to 25 May 2020); the Index to Scientific and Technical Proceedings (1980 to 2019); the Web of Science Core Collection; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) portal. We handsearched relevant journals and conference proceedings, checked reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials (RCTs) comparing one type of carotid patch with another for CEA. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, risk of bias, and trial quality; extracted data; and determined the quality of evidence using the GRADE approach. Outcomes, for example, perioperative ipsilateral stroke and long-term ipsilateral stroke (at least one year), were collected and analysed. MAIN RESULTS: We included 14 trials involving a total of 2278 CEAs with patch closure operations: seven trials compared vein closure with PTFE closure, five compared Dacron grafts with other synthetic materials, and two compared bovine pericardium with other synthetic materials. In most trials, a patient could be randomised twice and could have each carotid artery randomised to different treatment groups. Synthetic patch compared with vein patch angioplasty Vein patch may have little to no difference in effect on perioperative ipsilateral stroke between synthetic versus vein materials, but the evidence is very uncertain (odds ratio (OR) 2.05, 95% confidence interval (CI) 0.66 to 6.38; 5 studies, 797 participants; very low-quality evidence). Vein patch may have little to no difference in effect on long-term ipsilateral stroke between synthetic versus vein materials, but the evidence is very uncertain (OR 1.45, 95% CI 0.69 to 3.07; P = 0.33; 4 studies, 776 participants; very low-quality evidence). Vein patch may increase pseudoaneurysm formation when compared with synthetic patch, but the evidence is very uncertain (OR 0.09, 95% CI 0.02 to 0.49; 4 studies, 776 participants; very low-quality evidence). However, the numbers involved were small. Dacron patch compared with other synthetic patch angioplasty Dacron versus PTFE patch materials  PTFE patch may reduce the risk of perioperative ipsilateral stroke (OR 3.35, 95% CI 0.19 to 59.06; 2 studies, 400 participants; very low-quality evidence). PTFE patch may reduce the risk of long-term ipsilateral stroke (OR 1.52, 95% CI 0.25 to 9.27; 1 study, 200 participants; very low-quality evidence). Dacron may result in an increase in perioperative combined stroke and transient ischaemic attack (TIA) (OR 4.41 95% CI 1.20 to 16.14; 1 study, 200 participants; low-quality evidence) when compared with PTFE. Early arterial re-stenosis or occlusion (within 30 days) was also higher for Dacron patches. During follow-up for longer than one year, more 'any strokes' (OR 10.58, 95% CI 1.34 to 83.43; 2 studies, 304 participants; low-quality evidence) and stroke/death (OR 6.06, 95% CI 1.31 to 28.07; 1 study, 200 participants; low-quality evidence) were reported with Dacron patch closure, although numbers of outcome events were small. Dacron patch may increase the risk of re-stenosis when compared with other synthetic materials (especially with PTFE), but the evidence is very uncertain (OR 3.73, 95% CI 0.71 to 19.65; 3 studies, 490 participants; low-quality evidence). Bovine pericardium patch compared with other synthetic patch angioplasty Bovine pericardium versus PTFE patch materials  Evidence suggests that bovine pericardium patch results in a reduction in long-term ipsilateral stroke (OR 4.17, 95% CI 0.46 to 38.02; 1 study, 195 participants; low-quality evidence). Bovine pericardial patch may reduce the risk of perioperative fatal stroke, death, and infection compared to synthetic material (OR 5.16, 95% CI 0.24 to 108.83; 2 studies, 290 participants; low-quality evidence for PTFE, and low-quality evidence for Dacron; OR 4.39, 95% CI 0.48 to 39.95; 2 studies, 290 participants; low-quality evidence for PTFE, and low-quality evidence for Dacron; OR 7.30, 95% CI 0.37 to 143.16; 1 study, 195 participants; low-quality evidence, respectively), but the numbers of outcomes were small. The evidence is very uncertain about effects of the patch on infection outcomes. AUTHORS' CONCLUSIONS: The number of outcome events is too small to allow conclusions, and more trial data are required to establish whether any differences do exist. Nevertheless, there is little to no difference in effect on perioperative and long-term ipsilateral stroke between vein and any synthetic patch material. Some evidence indicates that other synthetic patches (e.g. PTFE) may be superior to Dacron grafts in terms of perioperative stroke and TIA rates, and both early and late arterial re-stenosis and occlusion. Pseudoaneurysm formation may be more common after use of a vein patch than after use of a synthetic patch. Bovine pericardial patch, which is an acellular xenograft material, may reduce the risk of perioperative fatal stroke, death, and infection compared to other synthetic patches. Further large RCTs are required before definitive conclusions can be reached.

Carotid endarterectomy for symptomatic carotid stenosis.

BACKGROUND: Stroke is the third leading cause of death and the most common cause of long-term disability. Severe narrowing (stenosis) of the carotid artery is an important cause of stroke. Surgical treatment (carotid endarterectomy) may reduce the risk of stroke, but carries a risk of operative complications. This is an update of a Cochrane Review, originally published in 1999, and most recently updated in 2017. OBJECTIVES: To determine the balance of benefit versus risk of endarterectomy plus best medical management compared with best medical management alone, in people with a recent symptomatic carotid stenosis (i.e. transient ischaemic attack (TIA) or non-disabling stroke). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Web of Science Core Collection, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) portal to October 2019. We also reviewed the reference lists of all relevant studies and abstract books from research proceedings. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing carotid artery surgery plus best medical treatment with best medical treatment alone.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted the data. We assessed the results and the quality of the evidence of the primary and secondary outcomes by the GRADE method, which classifies the quality of evidence as high, moderate, low, or very low. MAIN RESULTS: We included three trials involving 6343 participants. The trials differed in the methods of measuring carotid stenosis and in the definition of stroke. Using the primary electronic data files, we pooled and analysed individual patient data on 6092 participants (35,000 patient-years of follow-up), after reassessing the carotid angiograms and outcomes from all three trials, and redefining outcome events where necessary, to achieve comparability. Surgery increased the five-year risk of any stroke or operative death in participants with less than 30% stenosis (risk ratio (RR) 1.25, 95% confidence interval (CI) 0.99 to 1.56; 2 studies, 1746 participants; high-quality evidence). Surgery decreased the five-year risk of any stroke or operative death in participants with 30% to 49% stenosis (RR 0.97, 95% CI 0.79 to 1.19; 2 studies, 1429 participants; high-quality evidence), was of benefit in participants with 50% to 69% stenosis (RR 0.77, 95% CI 0.63 to 0.94; 3 studies, 1549 participants; moderate-quality evidence), and was highly beneficial in participants with 70% to 99% stenosis without near-occlusion (RR 0.53, 95% CI 0.42 to 0.67; 3 studies, 1095 participants; moderate-quality evidence). However, surgery decreased the five-year risk of any stroke or operative death in participants with near-occlusions (RR 0.95, 95% CI 0.59 to 1.53; 2 studies, 271 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: Carotid endarterectomy reduced the risk of recurrent stroke for people with significant stenosis. Endarterectomy might be of some benefit for participants with 50% to 69% symptomatic stenosis (moderate-quality evidence) and highly beneficial for those with 70% to 99% stenosis (moderate-quality evidence).

Age and sex-specific associations of carotid pulsatility with small vessel disease burden in transient ischemic attack and ischemic stroke.

Background Although large artery stiffness has been implicated in the pathogenesis of cerebral small vessel disease, whether carotid pulsatility, a convenient surrogate marker of arterial stiffness, is similarly associated with global burden of small vessel disease is unknown. Aims To determine the age and sex-specific associations of carotid pulsatility with global burden of small vessel disease. Methods We studied consecutive patients with transient ischemic attack or non-disabling ischemic stroke from the Oxford Vascular Study who had a brain MRI and carotid duplex ultrasound during 2002-2014. We determined clinical correlates of common carotid artery (CCA) and internal carotid artery (ICA) pulsatility index (PI) and their associations with the total small vessel disease score on MRI, stratified by age (median = 72). Results In 587 patients, correlates of CCA and ICA-PI were both independently associated with age, diabetes, and premorbid mean pulse pressure after adjustment for age, sex, and cardiovascular risk factors (all p < 0.05). ICA-PI was strongly associated with small vessel disease markers and burden, particularly lacunes, in patients aged<70 (age and sex-adjusted odds ratio of top vs. bottom pulsatility index quartile: 5.35, 1.95-14.70, p = 0.001; increasing small vessel disease score: 2.30, 1.01-5.25, p = 0.048), but not in patients aged ≥ 70 ( p > 0.05). No associations between CCA-PI with small vessel disease score were noted at any age. In 94 consecutive patients who also received transcranial Doppler ultrasound, strong associations between middle cerebral artery (MCA)-PI and an increasing small vessel disease score were noted (unadjusted OR-MCA: 4.26, 1.45-12.55, p = 0.009; ICA: 2.37, 0.81-6.87, p = 0.11; CCA: 1.33, 0.45-3.96, p=0.61). Conclusions ICA and MCA-PI are associated with global small vessel disease burden, especially in individuals aged<70 and may be causally related.

Symptomatic carotid atherosclerotic disease: correlations between plaque composition and ipsilateral stroke risk.

BACKGROUND AND PURPOSE: For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke. METHODS: In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk. RESULTS: No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11-1.89; P=0.02), fibrous content (0.65; 0.49-0.87; P=0.004), macrophage infiltration (1.41; 1.05-1.90; P=0.02), high microvessel density (1.49; 1.05-2.11; P=0.03), and overall plaque instability (1.40; 1.05-1.87; P=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk. CONCLUSIONS: Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification.