Recommendations for management of asymptomatic carotid artery disease (European Stroke Organisation et al. 2011):

Recommendations for management of symptomatic carotid artery disease:

Recommendations for selection of patients for carotid revascularization (Brott et al. 2011):

Recommendations for periprocedural management of patients undergoing carotid endarterectomy:

Recommendations for management of patients undergoing carotid artery stenting:

Recommendations for selection of patients for carotid revascularization (Kernan et al. 2014):

Abbott et al. (2015) systematically compared and appraised contemporary guidelines on management of asymptomatic and symptomatic carotid artery stenosis. They identified 34 guidelines meeting the inclusion criteria. These were sets of recommendations on CEA or CAS, or both for asymptomatic carotid stenosis (ACS) or symptomatic carotid stenosis (SCS), or both published between January 1, 2008, and January 28, 2015, in 41 separate documents from 23 different regions/countries (including 2 representing Europe and 5 the United States).

Mas et al. (2014) reported long-term follow-up results of patients included in the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial. This randomized, controlled trial of carotid stenting versus endarterectomy in 527 patients with recently symptomatic severe carotid stenosis was conducted in 30 centers in France. At the 5-year follow-up, the main end point (ipsilateral stroke after randomization or procedural stroke or death) had occurred in 29 of the 265 patients who were assigned to stenting and in 16 of the 262 patients who were assigned to endarterectomy (cumulative probability 11.0% versus 6.3%). At the 10-year follow-up, this end point had occurred in 30 patients in the stenting group and 18 in the endarterectomy group (cumulative probability 11.5% versus 7.6%). The long-term benefit-risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis favored endarterectomy, a difference driven by a lower risk of procedural stroke after endarterectomy. (The 30-day incidence of any stroke or death was 3.9% after endarterectomy and 9.6% after stenting (Mas et al. 2006)). Both techniques were associated with low and similar long-term risks of recurrent ipsilateral stroke beyond the procedural period.

The International Carotid Stenting Study (ICSS) enrolled 1713 patients (stenting group, n = 855; endarterectomy group, n = 858) (International Carotid Stenting Study Investigators et al. 2010). Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. In the intention to treat analysis, the risk of stroke, death, or procedural myocardial infarction 120 days after randomization was significantly higher in patients in the stenting group than in patients in the endarterectomy group (8.5% vs 5.2%). These early results suggested that carotid endarterectomy should remain the treatment of choice for symptomatic patients with severe carotid stenosis suitable for surgery. The ICSS trial was terminated in 2011. Patients were followed up for a median of 4.2 years after randomization (Bonati et al. 2015). In the ITT population, the primary endpoint of fatal or disabling stroke between randomization and end of follow-up was seen in 52 of 853 patients in the stenting group (cumulative 5-year risk 6.4%), and in 49 of 857 patients in the endarterectomy group (cumulative 5-year risk 6.5%). In the per-protocol population, no difference was seen between treatment groups in the rates of fatal or disabling stroke. The analysis showed that the risk of stroke of any severity occurring in any territory during follow-up was increased in the stenting group (excess risk 1.1% compared with endarterectomy at 1 year, and 3.1% at 5 years), but strokes were mainly non-disabling events. Thus, long-term functional outcome was similar for stenting and endarterectomy for symptomatic carotid stenosis. The authors concluded that endarterectomy remains the treatment of choice for older patients and those with extensive white-matter disease, but stenting is an appropriate treatment alternative for patients with symptomatic carotid stenosis if the risk of periprocedural stroke is low, for example in younger patients and those with lower levels of pre-existing white-matter disease. Moreover, there were no differences in costs or QALYs between the treatments (Featherstone et al. 2016).

Mechanisms of procedural stroke following carotid endarterectomy or carotid artery stenting within the ICSS trial were analyzed by Huibers et al. (2015). Procedural stroke occurred within 30 days of revascularization in 85 patients (CAS 58 out of 791 and CEA 27 out of 819). Nearly all (97%) of the strokes associated with CAS were the result of infarction. In contrast, in the surgery arm a much larger proportion of patients (18%) suffered from a haemorrhagic stroke. All haemorrhagic strokes in ICSS occurred several days after the procedure and most were preceded by severe hypertension. Nearly all strokes occurred in the ipsilateral hemisphere; however, a few (6) developed in a cerebral territory not directly related to the treated carotid artery. Non-ipsilateral strokes can be addressed to catheter-related disruption of the plaque in the aortic arch in patients undergoing CAS. In the CAS arm, stroke was most often caused by a haemodynamic mechanism.

The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) compared the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis (Brott et al. 2010). Patients were randomly assigned to one of the two treatments, resulting in a cohort of 2502 patients for all analyses. The primary end point was the composite of any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization. There was no significant difference in the estimated 4-year rates of the primary end point between carotid-artery stenting and carotid endarterectomy (7.2% and 6.8%, respectively). Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs 0.3%), for stroke (4.1% vs 2.3%), and for myocardial infarction (1.1% vs 2.3%). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively). Timaran et al. (2013) examined differences in outcomes between CAS and CEA performed by vascular surgeons in CREST. Vascular surgeons performed 237 of the 1136 CAS procedures (21%) and 765 of the 1184 CEAs (65%). Among randomized patients who underwent the assigned intervention performed by vascular surgeons, the periprocedural stroke and death rates were higher after CAS than CEA among symptomatic patients (6.1% vs 1.3%) and among asymptomatic patients (2.6% vs 1.1%). Conversely, MI rates were lower for CAS compared with CEA (1.3% vs 2.6%). Cranial nerve injuries (0.0% vs 5.0%) were less frequent after CAS than CEA. When vascular surgeons were compared with all other specialists performing CAS, they had comparable outcomes for the periprocedural primary end point (HR, 0.99) after adjusting for age, sex, and symptomatic status. Vascular surgeons also had similar results after CEA for the periprocedural primary end point compared with other specialists performing CEA (HR, 0.73).

Brott et al. (2016) now reported the outcomes after stenting and endarterectomy over 10 years of follow-up in the CREST trial. From 2000 through 2008, a total of 2502 patients underwent randomization. The median follow-up was 7.4 years. Consent for the long-term follow-up was obtained from 1607 patients. The 10-year risk of the primary composite endpoint (any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter) did not differ significantly between the stenting group and the endarterectomy group (hazard ratio in the stenting group, 1.10). At 10 years, the event rates were 11.8% in the stenting group and 9.9% in the endarterectomy group. There were no significant differences in the rate of the primary long-term end point – postprocedural ipsilateral stroke over the 10-year follow-up – between the stenting group and the endarterectomy group (6.9% and 5.6%, respectively; hazard ratio, 0.99). In the stenting group, the rate of stroke at 5 years was 2.5% among symptomatic patients and 2.5% among asymptomatic patients; the rates in the endarterectomy group were 2.7% among symptomatic patients and 2.7% among asymptomatic patients. In conclusion, over 10 years of follow-up no significant differences were seen between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke.

A Cochrane review assessed the benefits and risks of endovascular treatment compared with carotid endarterectomy or medical therapy in patients with symptomatic or asymptomatic carotid stenosis (Bonati et al. 2012). Sixteen trials involving 7572 patients were included. In patients with symptomatic carotid stenosis at standard surgical risk, endovascular treatment was associated with a higher risk of the following outcome measures occurring between randomisation and 30 days after treatment than endarterectomy: death or any stroke (odds ratio, OR 1.72), death or any stroke or myocardial infarction (OR 1.44), and any stroke (OR 1.81). The OR for the primary safety outcome was 1.16 in patients <70 years old and 2.20 in patients ≥70 years old. The rate of death or major or disabling stroke did not differ significantly between treatments (OR 1.28). Endovascular treatment was associated with lower risks of myocardial infarction (OR 0.44), cranial nerve palsy (OR 0.08) and access site haematomas (OR 0.37). The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up (the primary combined safety and efficacy outcome) favoured endarterectomy (OR 1.39), but the rate of ipsilateral stroke after the peri-procedural period did not differ between treatments (OR 0.93). Restenosis during follow-up was more common in patients receiving endovascular treatment than in patients assigned for surgery (OR 2.41). According to this review, endovascular treatment is associated with an increased risk of periprocedural stroke or death compared with endarterectomy. However, this excess risk appears to be limited to older patients.

Paraskevas et al. (2016) performed a systematic review using outcome data in large, administrative dataset registries. The main aims were to (i) compare stroke/death rates after CAS/CEA in contemporary dataset registries, (ii) examine whether procedural stroke/death rates had fallen within AHA/ASA thresholds, 1, 2 and 3 and (iii) determine whether there had been a decline (over time) in procedural risk after CEA/CAS. Stroke/death after CAS was significantly higher than after CEA in 11/21 registries (52%) involving “average risk for CEA” asymptomatic patients and in 11/18 registries (61%) involving “average risk for CEA” symptomatic patients. CAS was associated with stroke/death rates that exceeded risk thresholds recommended by the AHA in 9/21 registries (43%) involving “average risk for CEA” asymptomatic patients and in 13/18 registries (72%) involving “average risk for CEA” symptomatic patients. In conclusion, data from contemporary administrative dataset registries suggest that stroke/death rates following CAS remain significantly higher than after CEA and often exceed accepted AHA thresholds. There was no evidence of a sustained decline in procedural risk after CAS.

Tu et al. (2015) compared the outcomes of repeated CEA (redo CEA) and carotid artery stenting (CAS) for carotid restenosis (CRS) after CEA. Four thousand three-hundred and ninety-nine patients were included in this systematic review. No differences were observed in the 30-day perioperative mortality, stroke and transient ischemic attack rates in the comparative studies and the noncomparative studies. Patients undergoing redo CEA suffered more cranial nerve injuries (CNIs) than those undergoing CAS, but most of these cases recovered within 3 months. Patients treated with redo CEA exhibited similar myocardial infarction (MI) rates to those treated with CAS in the comparative studies, but the rate was higher in the noncomparative studies. Patients treated with CAS were more likely to develop restenosis than those treated with redo CEA in the long-term follow-up. In conclusion, both redo CEA and CAS were safe and feasible interventions for postendarterectomy restenosis. The main limitation of this systematic review was the lack of randomized, controlled trials. Another problem was the different follow-up period between the two groups. Furthermore, the influence of patients’ symptoms (symptomatic or asymptomatic) could not be analyzed.

Schermerhorn et al. (2013) analyzed 10,107 patients undergoing CEA (6370) and CAS (3737), stratified by Centers for Medicare and Medicaid Services (CMS) high-risk (HR) criteria (age ≥ 80 years/New York Heart Association (NYHA) congestive heart failure (CHF) class III/IV/left ventricular ejection fraction (LVEF) < 30%/recent myocardial infarction (within 30 days)/restenosis/radical neck dissection/contralateral occlusion/prior radiation to neck/contralateral laryngeal nerve injury/high anatomic lesion). The primary endpoint was composite death, stroke, and myocardial infarction (MI) (major adverse cardiovascular event [MACE]) at 30 days. CAS patients were more likely to have preoperative stroke (26% vs 21%) or transient ischemic attack (23% vs 19%) than CEA. Although age ≥80 years was similar, CAS patients were more likely to have all other HR criteria. CEA appeared safer for the majority of patients with carotid disease. For CEA, HR patients had higher MACEs than normal risk in both symptomatic (7.3% vs 4.6%) and asymptomatic patients (5% vs 2.2%). For CAS, HR status was not associated with a significant increase in MACE for symptomatic (9.1% vs 6.2%) or asymptomatic patients (5.4% vs 4.2%) (Table 1.1).

McDonald et al. (2014) determined whether adverse outcomes after CEA or CAS were similar using propensity score-matched analysis of retrospective data from a large hospital discharge database (Premier Perspective Database). After 1:1 propensity score matching, 24,004 (12,002 CEA and CAS) asymptomatic and 3506 (1753 CEA and CAS) symptomatic procedures were included. The risk of the modified primary composite end point (in-hospital mortality or stroke) was significantly higher for CAS recipients when compared with CEA recipients for both asymptomatic (2.5% versus 1.7%; hazard ratio for CAS, 1.49) and symptomatic (10.0% versus 3.5%, respectively; hazard ratio for CAS, 3.02) presentations. Acute myocardial infarction risk was not significantly different between revascularization therapies, regardless of clinical presentation.

Al-Damluji et al. (2015) examined frequency, timing, and diagnoses of 30-day readmission between patients undergoing CEA and CAS. Medicare fee-for-service administrative claims data were used. Of 180,059 revascularizations from 2287 hospitals, CEA and CAS were performed in 81.5% and 18.5% of cases, respectively. Crude 30-day readmission rates following CEA and CAS were 9.0% (13,222 of 146,831) and 12.0% (3980 of 33,228), respectively. Yet hospitals performing a greater proportion of revascularization via CAS did not have greater hospital 30-day risk-standardized readmission rates. Almost one-third of readmission diagnoses were potentially due to procedural complications, including cerebral events (10.7%), complications of care (8.6%), acute coronary syndrome (5.0%), and arrhythmias (4.0%).

Data from the Society for Vascular Surgery Vascular Registry were used by Jim et al. (2014) to determine the effect of gender on outcomes after CEA and CAS. There were 9865 patients (40.6% women) who underwent CEA (n = 6492) and CAS (n = 3373). The primary end point was a composite of death, stroke, and myocardial infarction at 30 days. For disease etiology in CAS, restenosis was more common in women (28.7% vs 19.7%), and radiation was higher in men (6.2% vs 2.6%). Comparing by gender, there were no statistically significant differences in the primary end point for CEA (women, 4.07%; men, 4.06%) or CAS (women, 6.69%; men, 6.80%). In this report, women did not have a higher risk of adverse events after carotid revascularization.

Datasets from 2005 to 2011 of the Nationwide Inpatient Sample (NIS) were queried for patients undergoing carotid revascularization by Eslami et al. (2015). The majority (95%) of the carotid revascularizations were performed on asymptomatic patients. Overall, CAS utilization constituted 12.5% of carotid revascularization procedures. In all three periods of the study, and compared to carotid endarterectomy, the odds of mortality and postoperative stroke were significantly higher among patients who underwent CAS. Wallaert et al. (2016a) used Medicare claims (2002–2010) to calculate annual rates of CAS and CEA and examined changes by procedure type over time. In total, data from 456,267 Medicare beneficiaries who underwent carotid revascularization between 2002 and 2010 were analyzed. The majority of these were CEA (88%). Overall, annual rates of carotid revascularization decreased by 30% over time (3.2 procedures per 1000 Medicare patients in 2002 vs 2.3 per 1000 in 2010). This decrease was largely attributable to a decline in the number of CEAs being performed. However, since its approval by the FDA in 2004, the rate of CAS has increased by 5% (0.30 vs 0.32 per 1000). In 2002, the majority of stents (54%) were placed by radiologists and the remaining 31% and 15% by cardiologists and surgeons, respectively. However, by 2010, this distribution shifted dramatically, with carotid stenting by radiologists declining to only 15% and both cardiologists and surgeons increasing their use of stenting to account for 49% and 36% of all stents placed. Carotid revascularization increased as the density of cardiologists increased.