Extracranial Carotid Stenosis
1. Randomized Studies on Open versus Endovascular Approach
The Asymptomatic Carotid Trial (ACT) I examined the outcomes after carotid endarterectomy (CEA) and carotid stenting (CAS) in asymptomatic patients with high-grade carotid stenosis [1]. Between 2005 and 2013, 1453 patients were included in this randomized study, 1089 in the CAS group, 364 in the CEA group. The study's endpoints were death, stroke, or myocardial infarction within 30 and 365 days after the procedure. Result: CAS was not inferior to CEA regarding the 30-day endpoint nor after 1 year.
Another randomized study comparing CEA and CAS is the CREST-Trial (Carotid Revascularization Endarterectomy versus Stenting Trial) [2]. The study included 2502 patients with asymptomatic as well as symptomatic carotid stenosis. Periprocedural strokes were more common after CAS than after CEA (4.1% vs. 2.3%), while myocardial infarctions were significantly less common (1.1% vs. 2.3%). After 10 years, the two groups did not differ significantly in the study endpoint (strokes of any kind, myocardial infarction or death periprocedurally or ipsilateral stroke in the further course) with 11.8% after CAS and 9.9% after CEA. Differences regarding symptoms (asymptomatic/symptomatic stenosis) between CAS and CEA were not observed. Differences regarding re-stenosis or revascularization after the procedure were also not significant: 12.2% after CAS and 9.7% after CEA.
In the randomized International Carotid Stenting Study (ICSS), CEA and CAS were compared in patients with recently preceding symptomatic carotid stenosis [3]. In total, 853 patients belonged to the CAS group, 857 to the CEA group. The incidence of stroke, death, or myocardial infarction was significantly higher in the CAS group at 8.5% within 120 days after the procedure than in the CEA group (5.2%). No differences were found between the two groups after a median of 4.2 years for severe re-stenoses or occlusions, although the rate of strokes of any severity in the CAS group remained significantly higher (CAS 15.2%, CEA 9.4%).
2. Meta-Analyses on Open versus Endovascular Approach
Regarding the question of effectiveness and safety of CAS and CEA in 3019 patients with asymptomatic carotid stenosis, there is a systematic review with meta-analysis from 2017 [4]. The incidences for periprocedural stroke and death showed a statistically borderline increased risk for CAS vs. CEA. In the long-term course, clinically relevant differences regarding stroke rate, death, and myocardial infarction could not be reliably excluded. It was concluded that CEA appears to be the safer and more effective procedure compared to CAS for the treatment of asymptomatic carotid stenosis. Another meta-analysis from 2017 and a third analysis from 2018 came to similar results [5, 6].
While the aforementioned analyses focused on 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 to CEA. Regarding long-term mortality from any cause and re-stenosis rate, no significant difference was found between CAS and CEA. Based on the results, CEA was recommended as the method of first choice in patients with carotid stenosis.
3. Registry Data
3.1. CEA vs. CAS
The care of the US Medicare population with CEA and CAS in the years 1999 to 2014 was reported in 2017 [8]. 937,111 patients underwent CEA, 231,077 underwent CAS. Over the observation period, the number of CEAs decreased, while the number of CAS increased. Regarding 30-day mortality, 30-day stroke, myocardial infarction or death, and the risk of an ischemic stroke after 1 year, the results improved despite increasing vascular risk factors. Interestingly, the number of procedures decreased over the observation period, which was explained by optimized medical therapy and higher health awareness.
Based on the Nationwide Inpatient Sample (NIS) from the years 2005 to 2011, the outcomes of CEA and CAS in high-risk patients were examined [9]. The data of 23,526 patients were considered, of which 3447 (14.7%) were treated with CAS, the rest with CEA. In over 90% of cases, an asymptomatic stenosis was present. The in-hospital mortality was 0.4%, with no difference between CAS (0.6%) and CEA (0.4%). However, in symptomatic patients, the in-hospital 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 performed in high-risk patients, but compared to CEA, this increased the periprocedural stroke rate in all high-risk patients and led to an additional increase in in-hospital mortality in symptomatic patients.
3.2. Influence of Contralateral Stenoses on CEA
Using the registry of the Vascular Study Group of New England (VSGNE) from the years 2003 to 2015, the influence of a contralateral stenosis and occlusion on the outcomes of CEA in 15,487 symptomatic and asymptomatic patients with carotid stenosis was examined [10]. The study concluded that a contralateral carotid occlusion did lead to a slightly increased stroke/mortality rate with CEA, but the contralateral occlusion should not be considered a high-risk criterion, as the 30-day rates of stroke/death in both symptomatic and asymptomatic patients remained within the limits specified by the guidelines.
3.3. Influence of Age and Gender on CEA
Based on the German quality assurance database, the influence of age and gender on the outcomes of CEA was examined [11]. 142,074 procedures from the years 2009 to 2014 were analyzed. The patients were predominantly male (68%) and on average 71 years old. The investigation showed that increasing patient age, but not gender, was associated with a higher perioperative risk of stroke or death after CEA. While the mortality risk was significantly associated only with patient age, this applied only to a very limited extent to the stroke risk. The perioperative neurological complications were significantly increased in older patients, but ultimately so low that age alone cannot represent an exclusion criterion for CEA.
The influence of patient age on the outcomes of CEA was also examined using the database of the Society for Vascular Surgery Vascular Quality Initiative (VQI) [12]. 7390 eighty- and ninety-year-olds were compared with 35,303 younger patients. The perioperative neurological complications were significantly increased in older patients, but ultimately low, so that age alone cannot represent an exclusion criterion for CEA. However, survival after 1 year was clearly less favorable at 93.74% compared to 97.18% in younger patients.
3.4. Early Carotid Revascularization by CEA
There is a study from 2017 that examined the "optimal" timing of CEA after the onset of neurological symptoms due to carotid stenosis [13]. In the database of the Vascular Study Group of New England (VSGNE), 989 symptomatic patients with carotid stenosis were found who underwent CEA within one month after the neurological event. If the CEA was performed less than 2 days after the onset of neurological symptoms, the rate of postoperative strokes was 7.3%, compared to 4.0% in the group with procedures after 2–5 days and 2.1% with procedures after ≥ 6 days. In the 1-year outcome, the groups did not differ. It was concluded to perform CEA to prevent a recurrent stroke as early as possible, but not in the first 2 days after the neurological event. An intervention was recommended still in the first week after the event.
An increased risk of CEA in the first 48 hours after the neurological event was also seen in the so-called Carotid Alarm Study [14].
3.5. CAS
In the ACS NSQIP database (American College of Surgeons National Surgical Quality Improvement Program), about 450 patients were identified in 2017 who underwent CAS for carotid stenosis [15]. The rate of adverse postoperative events was 7.1% after 30 days. Postoperative stroke or death was observed in 3.6% of asymptomatic and 2.8% of symptomatic patients. It was concluded that CAS can be performed in symptomatic patients, but not in asymptomatic patients, as the defined limits for postoperative death or stroke were exceeded in them. Older patients (> 80 years), women, patients of color, and those with more than one stent were exposed to an increased risk.
Another study reported on 13,086 CAS procedures recorded in the German quality assurance database from 2009 to 2014 [16]. Almost 64% of the procedures were performed in asymptomatic patients. Stroke or death was recorded periprocedurally 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 occurrence of neurological symptoms and the procedure was examined in a study based on 4717 elective procedures from the German quality assurance database [17]. The study showed that early CAS in the first 7 days after the neurological event was associated with an increased risk of stroke/death post-interventionally.