7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of carotid artery stenting : Jeffrey Jim, MD, MPHS, FACS : John F Eidt, MD, Joseph L Mills, Sr, MD : Kathryn A Collins, MD, PhD, FACS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 08, 2023. INTRODUCTION The proximal internal carotid artery and the carotid bifurcation are the locations most frequently affected by carotid atherosclerosis. Progression of atherosclerotic plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. This process can lead to cerebral ischemia (eg, transient ischemic attack, stroke) from arterial embolization, thrombosis, or less commonly from hemodynamic compromise. For patients with appropriate indications, options for carotid revascularization include carotid endarterectomy (CEA) or carotid angioplasty and stenting, which can be approached using several approaches, each with advantages and disadvantages. An overview of carotid artery stenting (CAS), including approaches to CAS and factors that may favor one approach over the other, and general issues surrounding periprocedural care are reviewed, including complications. CEA is reviewed elsewhere. (See "Carotid endarterectomy".) CAROTID ATHEROSCLEROTIC DISEASE The management of symptomatic or asymptomatic carotid atherosclerotic disease, including the indications for carotid revascularization and the choice between carotid endarterectomy [CEA] and CAS), is discussed in detail separately. (See "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic extracranial carotid atherosclerotic disease".) https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 1/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Indications for stenting CAS is an option for selected patients with contraindications to CEA due to high-risk anatomical or physiological factors for symptomatic ( 50 percent) or asymptomatic high-grade ( 80 percent) internal carotid artery stenosis. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid stenting' and "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CAS'.) Risk assessment Many of the risk factors for a worse outcome identified for CAS, such as symptomatic carotid disease, increasing degrees of carotid stenosis, parallel those identified in major trials of CEA. (See "Carotid endarterectomy", section on 'Risk factors for poor outcome'.) Other factors that may affect CAS outcomes in patients undergoing CAS include age, sex, composition and morphology of the stenotic lesion, and the presence of white matter lesions, among others. Age Data from the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial [1], Carotid Revascularization Endarterectomy versus Stent trial (CREST) [2-4], prospective series [5-7], and retrospective reports [8-10] suggest that patients 80 years old have a significantly higher risk of stroke and death at 30 days compared with younger patients following transfemoral CAS (TF-CAS). In addition, a retrospective study suggested that patients older than 80 had a higher incidence of unfavorable arterial factors that increased the technical difficulty of TF-CAS, such as aortic arch elongation, arch calcification, common carotid and innominate artery origin stenosis, common and internal carotid artery tortuosity, and a higher risk of residual stenosis post-stenting due to underlying vessel calcification [11]. It is also postulated that older patients have a lower cerebral reserve that makes them more sensitive to minor cerebral emboli, which may be one factor explaining their higher risk of stroke during TF-CAS [12]. Age does not appear to have an appreciable effect on patient outcomes after transcarotid artery revascularization (TCAR), which combines the benefits of avoiding a potentially diseased aortic arch with a low rate of distal embolization. The higher complication rates associated with age seen in those undergoing TF-CAS have not manifested among those undergoing the TCAR procedure. In a study evaluating all patients undergoing carotid procedures in the Vascular Quality Initiative between 2015 and November 2018, 10,381 TF- CAS cases (from 269 centers) and 3152 TCAR cases (from 174 centers) were evaluated [13]. The patients were divided into three different age groups: <70 years, 71 to 79 years, and >80 years. In-hospital mortality, stroke, myocardial infarction, and transient ischemic attack (TIA) were similar between the three age groups. TF-CAS was associated with an increased risk for stroke among older patients (>77 years) but TCAR was not. https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 2/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Sex Clinical studies indicate that the perioperative risk of CAS compared with CEA may be higher in females compared with males [14-18]. Studies are conflicting whether the perioperative risk associated with CAS is more prevalent in symptomatic or asymptomatic women, although data favor increased risk in symptomatic females. Sex as it may impact the choice of CAS or CEA in symptomatic and asymptomatic individuals is discussed in detail elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Factors influencing outcome' and "Management of symptomatic carotid atherosclerotic disease", section on 'Factors influencing benefit and risk'.) Composition and morphology of the stenotic lesion For patients with atherosclerotic disease, heavily calcified carotid plaque [19], ulcerated plaque [6], increasing degree of carotid stenosis [8], longer lesions, and presence of thrombus have been associated with an increased risk for stroke. Retrospective reviews also suggest that long carotid lesions (>10 mm) [8,20] or carotid segments with more than one lesion separated by normal vessel wall are associated with a higher stroke risk [8]. An analysis of plaque characteristics derived from the CREST trial reported that only plaque length was associated with age with respect to stroke risk; however, it was responsible for only 8 percent of the excess stroke risk [21]. Among patients with radiation-induced stenosis, a systematic review identified 27 studies including 533 patients who underwent CAS or CEA [22]. For patients who underwent TF- CAS, the pooled estimate for any cerebrovascular adverse event was 3.9 percent, which was similar to that identified for CEA. However, the rate of restenosis (long-term) >50 percent and/or occlusion was significantly higher in patients treated with CAS compared with CEA (22.5 versus 10.7 percent). An earlier meta-analysis that included 21 studies found similar results [23]. White matter lesions White matter lesions are likely a consequence of degenerative changes in the deep perforating arterioles. Risk factors for the development of white- matter lesions include age and hypertension. In the International Carotid Stenting Study (ICSS), the number of lesions identified on baseline brain imaging was correlated with stroke rates at 30 days [24]. Patients who underwent CAS with 7 age-related white matter changes had a higher risk of stroke relative to those with <7 lesions (hazard ratio [HR] 2.76, 95% CI 1.17-6.51) and relative to CEA (any stroke: HR 2.98, 95% CI 1.3-6.9; non-disabling stroke: HR 6.34, 95% CI 1.45-27.71). No differences in stroke rates were detected for those with <7 lesions. Other risk factors Other medical risk factors associated with an increased risk for periprocedural complications (mainly stroke) and worse outcome after TF-CAS have been https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 3/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate identified in uncontrolled prospective and retrospective studies. The assessment of medical risk prior to stenting and stroke risk associated with asymptomatic and symptomatic carotid stenosis are discussed in detail elsewhere. (See "Evaluation of cardiac risk prior to noncardiac surgery".) Other medical risk factors include [6,20,25-30]: Presence of aortic stenosis (may be an overall surrogate for atherosclerotic disease) Aortic arch calcification or variant aortic arch anatomy (transfemoral approach) Diabetes mellitus with inadequate glycemic control (hemoglobin A1C >7 percent) Symptomatic compared with asymptomatic ipsilateral carotid stenosis Hemispheric TIA or minor stroke compared with retinal TIA or no symptoms Chronic kidney disease Oral anticoagulant therapy Emergency admission Contraindications Contraindications to CAS can be grouped into those that contraindicate the procedure, in general, and those that contraindicate a specific approach (TF-CAS, TCAR). General contraindications are listed below. These and other specific contraindications are discussed in topics that discuss a specific approach [31] (see 'Indications for stenting' above and "Percutaneous carotid artery stenting", section on 'Contraindications for transfemoral approach' and "Transcarotid artery revascularization", section on 'Anatomic requirements and eligibility'): Absolute Visible thrombus within the lesion detected on preoperative imaging (eg, ultrasound, angiography) or intraoperative imaging Inability to gain vascular access Active infection Relative In general, relative contraindications to CAS include the following. Additional considerations depend upon the approach to carotid stenting. Severe plaque calcification, circumferential carotid plaque Severe carotid tortuosity Near occlusion of the carotid artery ( figure 1) [32,33] Small internal carotid artery (may not accommodate available commercial artery stents) Timing and other considerations The timing of intervention in patients with symptomatic carotid disease depends on the nature and severity of symptoms (eg, TIA, stroke) and is discussed separately. Although the periprocedural risks associated with CAS are similar to CEA https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 4/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate performed earlier (0 to 7 days), the stroke risk for CAS may be slightly higher [34,35]. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Timing of revascularization'.) Other considerations: Bilateral carotid stenosis For patients with severe bilateral carotid stenosis, we suggest a staged approach rather than simultaneous CAS [8,36,37]. A staged approach limits the length of the procedure and intravenous contrast load, whereas simultaneous CAS theoretically increases the risk for cerebral hyperperfusion syndrome and the risk of severe bradycardia or hypotension related to bilateral baroreceptor irritation [38]. (See 'Hyperperfusion syndrome' below.) Prophylactic carotid stenting Given that prophylactic CEA prior to another surgical procedure is generally not supported by available evidence, it may not be reasonable to offer CAS in this setting. A decision to proceed should be individualized based upon the risk of perioperative stroke weighed against the risk of bleeding associated with ongoing antiplatelet therapy (eg, clopidogrel, aspirin), which is recommended following CAS. (See "Coronary artery bypass grafting in patients with cerebrovascular disease", section on 'Method of carotid revascularization' and "Carotid endarterectomy", section on 'Carotid endarterectomy prior to other procedures' and 'Dual antiplatelet therapy' below.) APPROACH TO CAROTID ARTERY STENTING As experience using stents to treat atherosclerotic lesions at other peripheral sites increased, CAS was developed with the aim of reducing the systemic (eg, myocardial infarction [MI]) and local risks (eg, nerve injury) associated with carotid endarterectomy (CEA), which has been the established as the gold standard for carotid revascularization for atherosclerotic disease. To provide a durable benefit, the periprocedural risk of stroke and death for any carotid revascularization must be 3 percent for asymptomatic patients and 6 percent for symptomatic stenosis. (See "Management of asymptomatic extracranial carotid atherosclerotic disease" and "Management of symptomatic carotid atherosclerotic disease".) With the introduction of CAS, some outcomes improved with CAS, but stroke rates were increased in early trials, likely related to certain aspects of the stent technology, the conduct, the procedure (eg, crossing a diseased aortic arch), and possibly the nature of cerebral protection. Improvements in stent devices, differing access approaches, and differing embolic protection methods (distal filter protection, proximal flow arrest, proximal flow reversal) have all been https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 5/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate aimed at reducing the risk of stroke associated with CAS and stroke rates have improved for some, but not all patients. Alternative access approaches and technologic refinements continue. CAS can be performed percutaneously or through a small incision in the neck. Percutaneous CAS obtains vascular access through the groin (transfemoral), axillary artery (transaxillary), brachial artery (transbrachial), radial artery (transradial) [39-42], or direct puncture of the carotid (transcervical). By far the most common approach is via the right (or left) common femoral artery (ie, transfemoral CAS [TF-CAS]). Percutaneous approaches for CAS are typically performed in conjunction with a distal filter-type embolic protection device; proximal occlusion has also been used [43-45]. (See 'Transfemoral carotid revascularization' below and "Percutaneous carotid artery stenting".) Transcarotid artery revascularization (TCAR) is a specific technique that accesses the carotid through a short incision at the base of the neck over the proximal ipsilateral common carotid artery [43-61]. The TCAR procedure is performed through a short carotid sheath in conjunction with flow reversal for embolic protection using a proprietary device. (See 'Transcarotid revascularization' below and "Transcarotid artery revascularization".) Transfemoral carotid revascularization Clinical trials have compared CEA with TF-CAS in patients with either symptomatic or asymptomatic carotid disease [1,2,4,62-69]. No trials have compared CAS with medical therapy alone. Compared with CEA, the periprocedural risk for stroke, and possibly longer-term risk, following TF-CAS is higher [70-72]. Combined 30-day stroke and death rates for TF-CAS in randomized trials range from 6 to 9 percent for symptomatic and from 2 to 4 percent for asymptomatic patients [73-76]. Stroke rates have improved since the introduction of CAS, achieving long-term benefit for symptomatic and asymptomatic patients [73-76]. Clinical trials A meta-analysis of 16 trials (including CREST [2,4,68,69], ICSS [66,67], Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis [EVA- 3S] [63], Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy [SAPPHIRE] [64,65], and others) compared endovascular treatment (mainly TF-CAS) with CEA [74]. The risk of periprocedural stroke or death at 30 days was increased for CAS compared with CEA (8.2 versus 5.0 percent, odds ratio [OR] 1.72, 95% CI 1.29-2.31). In subgroup analysis, a higher risk of periprocedural stroke or death was seen for CAS patients 70 years of age compared with CEA (OR 2.20, 95% CI 1.47-3.29). By contrast, the risk of periprocedural stroke or death for patients <70 years of age was similar for CAS and CEA (OR 1.16, 95% CI 0.80-1.67). CAS had a higher rate of death or stroke during the periprocedural period or ipsilateral stroke during follow-up (10.4 versus 7.7 percent, OR 1.39, 95% CI 1.10-1.75), but a lower risk for MI (OR 0.44), https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 6/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate cranial nerve palsy (OR 0.08), and access site hematoma (OR 0.37). The randomized trials of carotid stenting in symptomatic and asymptomatic patients are discussed in more detail elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid stenting' and "Management of symptomatic carotid atherosclerotic disease", section on 'Trials comparing CAS with CEA'.) Registry data The 30-day death and stroke rate was 3.6 percent in an analysis of two multicenter postmarket surveillance registries of CAS (EXACT, CAPTURE-2) that included 6320 high-risk patients [77]. In the SAPPHIRE worldwide registry, which included 2001 patients followed for 30 days, mortality was 1.1 percent and stroke rate was 3.2 percent [78]. A similar rate was found in later large reviews [10,79-81]. Transcarotid revascularization The available clinical data on the TCAR procedure consist of safety and efficacy studies, institutional reports, and real-world outcomes found in the TCAR Surveillance Project (TSP). The updated Society for Vascular Surgery guidelines on the management of extracranial cerebrovascular disease note that TCAR procedure is at least equivalent to CEA, with some potential improvements, and compared with TF-CAS, the overall data demonstrate better outcomes [82]. TCAR may be preferable to CEA and TF-CAS for high-risk patients (anatomic and physiologic) [83]. Safety and efficacy studies The use of the TCAR procedure with internal carotid flow reversal was first described in 2004 [60,61]. However, the first report of TCAR performed with the neuroprotection system was published in 2011. The Silk Road Medical Embolic PROtectiOn System: First-In-Man (PROOF) study reported initial procedural success in 68 of 75 (91 percent) [43]. There were three device malfunctions and four artery dissections with device insertion. Of note, 9 percent had transient intolerance to flow reversal, which was managed successfully by minimizing the duration of flow reversal. At 30 days, there were no major strokes, MIs, or deaths [84]. In a subgroup of 31 patients who underwent a diffusion-weighted magnetic resonance imaging examination, 16 percent had evidence of new ischemic brain lesion without clinical sequelae. The Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) study was a prospective, single-arm, multicenter clinical trial that enrolled 208 patients considered at high risk for complications from CEA who had either symptomatic 50 percent stenosis or asymptomatic 70 percent stenosis [85]. Between 2012 and 2014, 67 patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase, and this latter group was evaluated for outcome analysis. The mean flow reversal time was 13 minutes, and there was one case (0.7 percent) of intolerance to high-flow reversal. The initial technical success rate was 99 percent and the all-stroke rate was 1.4 percent. The composite rate of https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 7/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate stroke/death was 2.8 percent, and the composite rate of stroke/death/MI was 3.5 percent. One patient (0.7 percent) had postoperative hoarseness from potential 10th cranial nerve injury, which resolved at six months. In a follow-up study, 165 patients (112 of 141 pivotal ROADSTER patients as well as 53 of 78 extended-access patients) had outcomes analyzed at one year [86]. Patients aged 75 years and older comprised 43.3 percent of the cohort; 79.9 percent were asymptomatic. In this group, the ipsilateral incidence of stroke incidence was 0.6 percent; seven patients (4.2 percent) died during follow-up, but none of the deaths were neurologic in origin. The ROADSTER 2 study was a prospective, single-arm, multicenter post-approval registry that enrolled 692 patients between 2015 and 2019. Patients were considered at high risk for complications from CEA with either symptomatic 50 percent stenosis or asymptomatic 80 percent stenosis. In the "per protocol" study population, which included 632 patients (ie, 60 protocol violations excluded), the primary endpoint of procedural success (ie, technical success plus absence of stroke/death/MI) was 97.9 percent [87,88]. In the per protocol group, the perioperative (30-day) stroke rate was 0.6 percent, the composite rate of stroke/death was 0.8 percent, and composite rate of stroke/death/MI was 1.7 percent. Observational studies Outcomes for the TCAR procedure appear to be at least equivalent to CEA in observational studies. In a multi-institutional analysis of patients undergoing TCAR and CEA at four institutions, 663 consecutive patients were identified. TCAR patients had higher prevalence of several comorbidities (diabetes, hyperlipidemia, coronary disease, and renal insufficiency). The stroke rates were similar at 30 days (1.0 percent TCAR versus 1.1 percent CEA) and one year (2.8 percent TCAR and 3.0 percent CEA) in the unmatched groups. The patients were then propensity matched based on preoperative comorbidities. In comparing 292 TCAR with 292 CEA patients, stroke (1.0 percent TCAR versus 0.3 percent CEA) and death (0.3 percent TCAR versus 0.7 percent CEA) were similar at 30 days and comparable at one year (stroke 2.8 percent TCAR versus 2.2 percent CEA and death 1.8 percent TCAR versus 4.5 percent CEA). The two groups had a similar composite endpoint of stroke/death/MI (2.1 percent TCAR versus 1.7 percent CEA), but TCAR was associated with a decreased rate of cranial nerve injury (0.3 percent TCAR versus 3.8 percent CEA) [89]. TCAR surveillance project The TSP remains the largest source of data on the clinical outcome of TCAR. Although not all CEA and TF-CAS procedures are captured within the VQI, over 95 percent of all TCAR procedures performed in the United States are recorded in this registry [90]. Several studies have used data from the TSP to compare outcomes between the different methods of carotid revascularization. TCAR versus CEA In a TSP study comparing in-hospital outcomes for patients treated between January 2016 and March 2018, 1182 TCAR patients were compared with 10,797 CEA https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 8/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate patients. TCAR patients were older, more likely symptomatic, and had more medical comorbidities (including coronary artery disease, heart failure, and lung and kidney disease). TCAR patients were more likely to undergo redo carotid intervention, given higher rates of prior ipsilateral CEA (16 versus 2 percent) [91]. TCAR patients were more often treated with local or regional anesthesia (20 versus 7 percent). On unadjusted analysis, TCAR had a similar rate of in- hospital stroke/death (1.6 versus 1.4 percent) and stroke/death/MI (2.5 versus 1.9 percent) compared with CEA. There was no difference in the rate of stroke (1.4 versus 1.2 percent), in- hospital death (0.3 versus 0.3 percent), 30-day death (0.9 versus 0.4 percent), or MI (1.1 versus 0.6 percent). TCAR on average was 33 minutes shorter than CEA, and the patients were less likely to incur a cranial nerve injury (0.6 versus 1.8 percent). On adjusted analysis, there was no difference in terms of stroke/death, stroke/death/MI, or the individual outcomes [92]. TCAR versus TF-CAS In a TSP study that compared in-hospital outcomes for 638 patients undergoing TCAR from 2016 to 2017 with 10,136 patients who underwent TF-CAS between 2005 and 2017 [93], TCAR patients were found to be significantly older, had more cardiac comorbidities, were more likely to be symptomatic, and were less likely to have recurrent stenosis. TCAR procedures were more likely to be performed under general anesthesia (79 versus 12 percent) compared with TF-CAS. TCAR was associated with overall lower rates of in- hospital transient ischemia attacks (TIA)/stroke (1.9 versus 3.3 percent) and in-hospital TIA/stroke/death (2.2 versus 3.8 percent) compared with TF-CAS. On multivariate analysis, there was a trend but no statistically significant difference in stroke or death rates. In a later TSP study using data between September 2016 and April 2019, there were 5251 TCAR procedures performed by 1035 surgeons from 319 centers [90]. Most procedures were performed by vascular surgeons (85 percent), followed by general surgeons (9 percent), neurosurgeons (2 percent), and cardiologists (1 percent). TCAR accounted for 46 percent of all carotid stenting procedures performed in 2018. There were 6640 TF-CAS patients included in the study. After propensity score matching, 3286 pairs of patients were identified. TCAR was associated with a lower risk of in-hospital stroke or death (1.6 versus 3.1 percent), stroke (1.3 versus 2.4 percent), and death (0.4 versus 1 percent). There was no statistically significant difference in the risk of perioperative MI (0.2 versus 0.3 percent). The TCAR procedure was also associated with less radiation exposure for the patient and less contrast utilized. At one year, TCAR also had a lower risk of ipsilateral stroke or death (5.1 versus 9.6 percent). Selecting an approach Anatomic evaluation The evaluation of patients who may be candidates for CAS includes preoperative vascular imaging to characterize the carotid lesion and assure its patency, evaluate https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 9/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate surrounding anatomy, and identify anatomic features that may influence the approach to CAS. (See "Evaluation of carotid artery stenosis".) The evaluation of the carotid lesion may include duplex ultrasonography, computed tomographic (CT) angiography, or magnetic resonance imaging or catheter angiography depending on the clinical presentation (symptomatic, asymptomatic). These are typically sufficient to characterize the carotid lesion and surrounding anatomy. For TCAR, ultrasound examination of the neck also confirms adequate anatomy for arterial sheath insertion. For TF-CAS, CT angiography identifies any significant aortoiliac occlusive disease. For patients with occlusive disease, a decision needs to be made whether transfemoral access is feasible, or whether adjunctive endovascular procedure (eg, iliac artery angioplasty/stenting) is needed to safely achieve access. For some patients, an alternative access route may need to be selected. For TCAR, CT angiography defines anatomic candidacy related to the length of common carotid artery, presence of aortic arch atheroma, vessel tortuosity, and calcium burden within the carotid lesion. Cross-sectional contrast-enhanced imaging from the aortic arch through to the Circle of Willis should also be performed to identify the presence of intracranial arterial disease that may affect patient outcome. Factors favoring TF-CAS For patients in whom CAS has been selected, the following factors may favor the TF-CAS. Severe radiation injury in the neck Prior neck ablative surgery (laryngectomy with tracheostomy or radical neck dissection) The degree of radiation damage to the soft tissue in a patient who has undergone prior neck irradiation should be considered when selecting an approach for CAS. The TCAR procedure may be avoided because it requires limited dissection through a neck incision. Patients with prior neck irradiation tolerate TF-CAS with relative safety [5,94-96]. However, in many [97-99], but not all, studies [100,101], the rate of late carotid restenosis and occlusion following CAS was higher in patients who had radiation-induced occlusive disease compared with those who had atherosclerotic carotid disease [98]. A systematic review identified 27 studies that included 533 patients with radiation-induced carotid stenosis who underwent CAS or CEA [22]. Among patients who underwent TF-CAS, the pooled estimate for any cerebrovascular adverse event was 3.9 percent, which was similar to that identified for CEA. However, the rate of restenosis >50 percent and/or occlusion was significantly higher in patients treated with CAS compared with https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 10/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate CEA (22.5 versus 10.7 percent). An earlier meta-analysis that included 21 studies found similar results [23]. However, carotid restenosis and occlusion in these reports was largely asymptomatic. Factors favoring TCAR For patients in whom CAS has been selected, the following factors may favor the TCAR procedure. Peripheral arterial disease with unfavorable peripheral artery (eg iliac, femoral) access Heavily calcified, severely ulcerated or thrombus-lined aortic arch Likely inability to track and deploy a distal cerebral protection device because of marked tortuosity of the proximal internal carotid artery Variations in aortic arch anatomy, such as a type III arch or bovine anatomy Patients with marked truncal obesity with groin colonization with bacteria and yeast Age >80 PERIOPERATIVE CARE Transfemoral CAS (TF-CAS) is most commonly performed using local anesthesia with sedation and close cardiopulmonary monitoring by the anesthesia provider. It is important for the patient to be able to communicate freely during the procedure with the anesthesia provider. The patient needs to be comfortable, but not so heavily sedated that they are disinhibited or unable to follow commands. Transcarotid artery revascularization (TCAR) may be more commonly performed using general anesthesia. In a study looking at 2609 patients undergoing TCAR, 82.3 percent were performed with general anesthesia and 17.7 percent under local anesthesia with no differences in clinical outcomes (eg, mortality, myocardial infarction [MI], neurologic events) [102]. General anesthesia is generally recommended for TCAR proceduralists early during their experience; however, when procedural familiarity is obtained, TCAR is well suited for use of local anesthesia as with TF-CAS. (See "Anesthesia for carotid endarterectomy and carotid stenting".) Some degree of periprocedural bradycardia or hypotension occurs in up to 68 percent of patients who undergo CAS [103-110]. Given that bradycardia or even cardiac arrest can develop during ballooning of the stent, both atropine and glycopyrrolate should be available for immediate infusion. Bradycardia is due to carotid baroreceptor stimulation during inflation of the post-stent angioplasty balloon. Following CAS, patients are typically discharged in one to two days. Outpatient CAS may become feasible, but the safety of this practice needs to be established. Reimbursement in the United States for CAS mandates an overnight hospitalization of at least one day. https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 11/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Medication management Preoperative control of blood pressure Poorly controlled hypertension preoperatively is predictive of prolonged length of stay due to postoperative hypertension. Thus, we make an effort to have hypertension under control before proceeding with CAS [111]. (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Hemodynamic monitoring'.) Prophyactic antibiotics Although not routinely recommended for all percutaneous interventional procedures, antibiotic prophylaxis prior to CAS is standard practice, regardless of approach. Appropriate antibiotic choices are given in the table ( table 1). Dual antiplatelet therapy Prior to CAS, we recommend pretreatment with dual antiplatelet therapy (DAPT) using aspirin and clopidogrel ( algorithm 1); however, data are limited regarding the effectiveness of DAPT; the optimal timing, dose and duration of treatment for CAS is unknown [112]. Our specific pretreatment and post-treatment dosing regimens for percutaneous CAS and TCAR are provided separately. (See "Percutaneous carotid artery stenting", section on 'Antiplatelet/statin therapy' and "Transcarotid artery revascularization", section on 'Dual antiplatelet therapy and statins'.) A systematic review identified only two small trials comparing single with dual antiplatelet therapy in patients undergoing CAS. In a meta-analysis of these two trials [113-115], the risk for transient ischemic attack (TIA) was reduced for dual compared with single antiplatelet therapy (1.3 versus 14.6 percent; risk difference -0.13; 95% CI -0.22 to -0.05). However, there were no differences in stroke, major bleeding, or hematoma formation, or incidence of MI or death. In a separate meta-analysis of these same trials, the risk for restenosis was similar [116]. In the absence of any other robust data, we initiate DAPT using aspirin and clopidogrel prior to the procedure (at least 48 hours for percutaneous CAS; the TCAR trial favored 72 hours pretreatment) and continue dual antiplatelet therapy post-procedure for at least four weeks. Thereafter, aspirin should be continued indefinitely to reduce the risk for future cardiovascular events. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Antiplatelet therapy'.) In an observational study from the Vascular Quality Initiative looking at 31,036 total CAS procedures (approximately 50/50 TCAR and TF-CAS), perioperative P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor taken within 36 hours of the procedure) markedly reduced the perioperative neurologic event rate [117]. Among patients on P2Y12 inhibitors, 92.7 percent were also taking aspirin. P2Y12 inhibitors were significantly more likely to be used in TCAR cases compared with TF-CAS cases (87.3 versus 76.8 percent). Of the patients on P2Y12 inhibitors, 77.3 https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 12/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate percent were on clopidogrel. This study demonstrated there is considerable room for improving compliance with recommended perioperative DAPT. For patients with a history of neck irradiation, we suggest long-term DAPT with aspirin and clopidogrel following CAS, provided the risk of bleeding remains low. While there are no studies available that have specifically evaluated such a protocol in this subset of patients, radiated patients are at high risk for recurrent carotid stenosis following CAS, as high as 30 percent in some series. In CAS trials, the following protocols were used: In the CREST trial, patients were treated with aspirin (325 mg twice daily) and clopidogrel (75 mg twice daily) starting at least 48 hours before the CAS procedure [4]. Those scheduled for CAS within 48 hours received aspirin 650 mg and clopidogrel 450 mg at least four hours before the CAS procedure. Following CAS, treatment included aspirin 325 mg once or twice daily and clopidogrel 75 mg daily (or ticlopidine 250 mg twice daily) for at least 30 days, with a recommendation to continue aspirin indefinitely (at least one year). In a survey of participants of the Asymptomatic Carotid Surgery Trial 2 (ACST2 trial), 82 percent of sites used dual antiplatelet therapy (DAPT) preoperatively and 86 percent postoperatively with a mean postprocedural duration of three months (range 1 to 12), while 9 percent continued DAPT lifelong [118]. For those prescribing postprocedural mono antiplatelet therapy (76 percent), aspirin was more commonly prescribed than clopidogrel (59 versus 6 percent), and 11 percent did not show a preference for either aspirin or clopidogrel. Eleven centers (16 percent) tested for antiplatelet therapy resistance. In the ROADSTER 2 study, early postoperative outcomes in the intention-to-treat population (692 patients) included stroke in 13 patients (1.9 percent), death in 3 patients (0.4 percent), and MI in 6 patients (0.9 percent) [88]. Sixty patients had major protocol deviations, and among these, 48 patients were not on dual antiplatelet and statin therapy while undergoing carotid intervention or during the periprocedural follow-up period. Among the 60 patients with protocol violations, perioperative (30-day) stroke occurred in 9 (26 percent); death in 2 (3.3 percent); MI in none. Guidelines have suggested a range of periprocedural aspirin therapy ranging from 75 mg to 325 mg daily [82,83,119,120]. Various loading doses of clopidogrel have also been used. Other doses of clopidogrel have also been investigated. In the Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting (ARMYDA-9 CAROTID) trial, 156 patients were randomly assigned to receive a loading dose of clopidogrel (600 mg or 300 mg) before stenting https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 13/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate with or without a statin reload (2 x 2 trial design) [121]. The perioperative (30-day) incidence of TIA/stroke or new ischemic lesions on magnetic resonance imaging was lowest in the 600 mg clopidogrel plus statin reload group. By contrast, in a smaller trial, no differences were seen between groups for asymptomatic patients (n = 35) undergoing CAS assigned to 300 mg or 600 mg of clopidogrel with respect to the sum of all microembolic signals on transcranial Doppler, or platelet aggregation measurements [122]. Cilostazol is a phosphodiesterase inhibitor that is commonly used in the treatment of claudication. A systematic literature review identified seven studies evaluating outcomes using cilostazol in association with CAS [123]. Major outcomes included in-stent restenosis within the observation period, revascularization rate, major/minor bleeding, and MI/stroke/death rate at 30 days and within the observation period. A significantly lower rate of in-stent stenosis was seen with cilostazol treatment after a mean follow-up of 20 months (odds ratio [OR] 0.158, 95% CI 0.072-0.349). No significant differences were found between the groups among five studies (649 patients) for periprocedural MI/stroke/death or in three studies (1076 patients) for MI/stroke/death for the entire follow-up period. Statin therapy Statin therapy is recommended for patients following TIA or ischemic stroke or in those with coronary artery disease risk equivalents. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease" and "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy'.) Whether statin therapy can reduce the risk of cerebral embolization during or after CAS is debated [121,124-129]. A small study compared debris collected from embolic protection devices in 62 patients who were or were not taking statins [129]. Statin use (HMG-CoA-reductase inhibitor) was associated with significantly fewer embolic particles (16.4 versus 42.4 particles).