Extracranial carotid stenosis
1. Randomized trials on open versus endovascular procedures
The Asymptomatic Carotid Trial (ACT) I studied the outcome after carotid endarterectomy (CEA) and carotid artery stenting (CAS) in asymptomatic patients with severe carotid stenosis [1]. Between 2005 and 2013, 1,453 patients were enrolled in this randomized study, 1,089 in the CAS group and 364 in the CEA group. Endpoints of the trial were death, stroke or myocardial infarction during 30 and 365 days post-procedure. Outcome: CAS was not inferior to CEA either in terms of the 30-day endpoint or after 1 year.
Another randomised study comparing CEA and CAS is the CREST Trial (Carotid Revascularization Endarterectomy versus Stenting Trial) [2]. The trial included 2502 patients with both asymptomatic and symptomatic carotid stenosis. Periprocedural strokes were more frequent after CAS than after CEA (4.1% vs. 2.3%), whereas myocardial infarctions were, conversely, significantly less common (1.1% vs. 2.3%). After 10 years, the two groups did not differ significantly in the study endpoint (stroke of any type, myocardial infarction or death periprocedurally, or ipsilateral stroke during subsequent follow-up), with 11.8% after CAS and 9.9% after CEA. No differences were seen between CAS and CEA with regard to symptoms (asymptomatic/symptomatic stenosis). Likewise, the differences regarding restenosis or revascularisation after the procedure were not significant: 12.2% after CAS and 9.7% after CEA.
The randomised International Carotid Stenting Study (ICSS) compared CEA and CAS in patients with recently symptomatic carotid stenosis [3]. A total of 853 patients were in the CAS group and 857 in the CEA group. The incidence of stroke, death or myocardial infarction within 120 days of the procedure was significantly higher in the CAS group at 8.5% than in the CEA group (5.2%). After a median of 4.2 years, the two groups did not differ in severe restenosis or occlusion, but the rate of stroke of any severity remained significantly higher in the CAS group (CAS 15.2%, CEA 9.4%).
2. Meta-analyses on open versus endovascular procedures
A systematic review with meta-analysis from 2017 addressed the question of the efficacy and safety of CAS and CEA in 3019 patients with asymptomatic carotid stenosis [4]. The incidences of periprocedural stroke and death revealed a statistically borderline increased risk for CAS vs. CEA. Over the long term, clinically significant differences in the rates of stroke, death and myocardial infarction could not be excluded with certainty. It was concluded that, compared with CAS, CEA appears to be the safer and more effective procedure for treating asymptomatic carotid stenosis. Another meta-analysis from 2017 and a third analysis from 2018 arrived at similar results [5, 6].
While the aforementioned analyses related to patients with asymptomatic carotid stenosis, a meta-analysis from 2017 included 7005 patients with asymptomatic and symptomatic stenosis [7]. In the study, CAS was associated with a significantly lower risk of myocardial infarction but with a higher risk of stroke and death compared with CEA. No significant difference was found between CAS and CEA with regard to long-term all-cause mortality and restenosis rate. Based on these results, CEA was recommended as the method of first choice in patients with carotid stenosis.
3. Registry data
3.1. CEA vs. CAS
Treatment of the US Medicare population by CEA and CAS between 1999 and 2014 was reported in 2017 [8]. 937,111 patients underwent CEA and 231,077 underwent CAS. Over the observation period, the number of CEA cases decreased while the number of CAS cases increased. Regarding 30-day mortality, 30-day stroke, myocardial infarction or death, and the risk of ischaemic stroke after 1 year, outcomes improved despite increasing vascular risk factors. Interestingly, the number of procedures decreased over the observation period, which was attributed to optimised medical therapy and greater health awareness.
Based on the Nationwide Inpatient Sample (NIS) from 2005 to 2011, the outcomes of CEA and CAS were investigated in high-risk patients [9]. Data from 23,526 patients were included, of whom 3,447 (14.7%) were treated with CAS and the remainder with CEA. Asymptomatic stenosis was present in over 90% of cases. Inpatient mortality was 0.4%, with no difference between CAS (0.6%) and CEA (0.4%). However, in symptomatic patients, inpatient mortality was significantly higher with CAS than with CEA (4.7% vs. 2.0%). The periprocedural stroke rate was 0.9% and was significantly higher with CAS (1.4% vs. 0.9%). However, the rate did not differ in symptomatic patients. Over the observation period, the number of procedures performed annually remained stable, while the number of high-risk patients treated increased slightly but significantly. As expected, the proportion of CAS increased over the observation period, with a corresponding decrease in CEA. It was concluded that CAS was increasingly being performed in high-risk patients, but that, compared with CEA, this increased the periprocedural stroke rate in all high-risk patients and led to an additional increase in inpatient mortality in symptomatic patients.
3.2. Impact of contralateral stenoses on CEA
Based on the registry of the Vascular Study Group of New England (VSGNE) from 2003 to 2015, the impact of contralateral stenosis and occlusion on CEA outcomes was investigated in 15,487 symptomatic and asymptomatic patients with carotid stenosis [10]. The study concluded that although contralateral carotid occlusion led to a slightly increased stroke/mortality rate in CEA, contralateral occlusion should nonetheless not be regarded as a high-risk criterion, since the 30-day rates of stroke/death in both symptomatic and asymptomatic patients remained within the limits stated by the guidelines.
3.3. Impact of age and gender on CEA
Based on the German quality assurance database, the impact of age and sex on CEA outcomes was studied [11]. A total of 142,074 procedures performed between 2009 and 2014 were analysed. The patients were predominantly male (68%) with a mean age of 71 years. The study found that increasing patient age, but not sex, was associated with a higher perioperative risk of stroke or death following CEA. While the mortality risk alone was significantly associated with patient age, this was only true to a very limited extent for the risk of stroke. Although perioperative neurological complications were significantly more common in older patients, they were ultimately so low that age alone cannot constitute an exclusion criterion for CEA.
The impact of patient age on CEA outcomes was also reviewed using the Society for Vascular Surgery Vascular Quality Initiative (VQI) database [12]. A total of 7,390 patients in their eighties and nineties were compared with 35,303 younger patients. Although perioperative neurological complications were significantly more common in older patients, they were ultimately low, so that age alone cannot constitute an exclusion criterion for CEA. However, one-year survival was considerably less favourable at 93.74% compared with 97.18% in the younger patients.
3.4. Early carotid revascularisation by CEA
A study from 2017 investigated the "optimal" timing of CEA after the onset of neurological symptoms due to carotid stenosis [13]. The database of the Vascular Study Group of New England (VSGNE) included 989 symptomatic patients with carotid stenosis who underwent CEA within one month of their neurological event. If CEA was performed less than 2 days after the onset of neurological symptoms, the rate of postoperative stroke was 7.3%, compared with 4.0% in the group undergoing surgery after 2–5 days and 2.1% for procedures after ≥ 6 days. The groups did not differ in their outcome after 1 year. It was concluded that CEA to prevent recurrent stroke should be performed as early as possible, but not within the first 2 days after the neurological event. Intervention within the first week after the event was recommended.
An increased risk of CEA in the first 48 hours after the neurological event was also observed in the so-called Carotid Alarm Study [14].
3.5. CAS
The ACS NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database identified approximately 450 patients who had undergone CAS in 2017 for carotid stenosis [15]. The rate of adverse postoperative events after 30 days was 7.1%. Postoperative stroke or death was observed in 3.6% of asymptomatic and in 2.8% of symptomatic patients. It was concluded that while CAS can be performed in symptomatic patients, this is not the case in asymptomatic patients, as in the latter the defined thresholds for postoperative death or stroke were exceeded. Older patients (> 80 years of age), women, patients of colour, and those with more than one stent were at particularly increased risk.
Another study reported on 13,086 CAS procedures recorded in the German quality assurance database between 2009 and 2014 [16]. Almost 64% of the procedures were performed in asymptomatic patients. Periprocedural stroke or death was recorded in 1.7% of asymptomatic and 3.7% of symptomatic patients. The use of an embolic protection system was associated with a significant reduction in death and stroke.
The dependence of the postoperative outcome in CAS on the time interval between the onset of neurological symptoms and the procedure was investigated in a study of 4717 elective procedures from the German quality assurance database [17]. The study demonstrated that early CAS within the first 7 days after the neurological event was associated with an increased risk of postinterventional stroke/death.