Extracranial carotid stenosis
1. Randomized trials on open versus endovascular procedures
The Asymptomatic Carotid Trial (ACT) I evaluated outcomes after carotid endarterectomy (CEA) and carotid stenting (CAS) in asymptomatic patients with high-grade carotid stenosis [1]. This randomized trial enrolled 1453 patients between 2005 and 2013, 1089 in the CAS group and 364 in the CEA group. The endpoints of the study were death, stroke, or myocardial infarction within 30 and 365 days post intervention. Outcome: CAS was not inferior to CEA with respect to either the 30-day end point or at 1 year.
Another randomized trial comparing CEA and CAS was the CREST trial (Carotid Revascularization Endarterectomy versus Stenting Trial) [2]. The trial enrolled 2502 patients with asymptomatic as well as symptomatic carotid stenosis. Periprocedural stroke was more common following CAS than after CEA (4.1% vs. 2.3%); in contrast, myocardial infarction was significantly less frequent (1.1% vs. 2.3%). At 10 years, both groups did not differ significantly in the study end point (periprocedural stroke of any type, myocardial infarction, or death, or subsequent ipsilateral stroke), with 11.8% in CAS and 9.9% in CEA. CAS and CEA did not differ in terms of symptoms (asymptomatic/symptomatic stenosis). Nor were there any significant differences regarding postprocedural restenosis or revascularization: 12.2% following CAS and 9.7% after CEA.
The randomized 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%). At a median of 4.2 years, there were no differences between the two groups regarding severe restenosis or occlusion; however, 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
There is one systematic review with meta-analysis from 2017 regarding the efficacy and safety of CAS and CEA in 3019 patients with asymptomatic carotid stenosis [4]. The rates of periprocedural stroke and death revealed an increase in risk for CAS vs. CEA of borderline statistical significance. The long-term follow-up did not reliably rule out clinically significant differences in the rates of stroke, death, and myocardial infarction. The authors concluded that CEA appeared to be the safer and more effective procedure in the management of asymptomatic carotid artery stenosis compared with CAS. Another meta-analysis from 2017 and a third analysis from 2018 reached similar conclusions [5, 6].
While the above analyses referred to patients with asymptomatic carotid stenosis, a 2017 meta-analysis studied 7005 patients with asymptomatic and symptomatic stenosis [7]. In that study, CAS was associated with significantly lower risk of myocardial infarction but 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 first-line modality in patients with carotid stenosis.
3. Registry data
3.1. CEA vs. CAS
In 2017, a report was published addressing the treatment of the U.S. Medicare population with CEA and CAS from 1999 to 2014 [8]. 937,111 patients underwent CEA, and 231,077 underwent CAS. During the period observed, the number of CEA cases decreased and the number of CAS cases increased. With regard to 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 enough, the number of procedures decreased over the period observed, which was explained by optimised drug therapy and better health awareness.
The outcomes of CEA and CAS in high-risk patients were examined based on the Nationwide Inpatient Sample (NIS) from 2005 to 2011 [9]. Data from 23,526 patients were included, of whom 3447 (14.7%) underwent CAS and the remainder CEA. More than 90% of cases presented with asymptomatic stenosis. In-hospital mortality was 0.4%, with no difference between CAS (0.6%) and CEA (0.4%). However, in symptomatic patients, 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 in CAS (1.4% vs. 0.9%). However, the rate did not differ in symptomatic patients. During the period observed, the number of procedures performed annually remained stable, while the number of treated high-risk patients increased slightly, but significantly. As expected, the share of CAS increased over the observation period, with a corresponding decrease in CEA. The authors concluded that CAS was increasingly performed in high-risk patients, but that this increased the periprocedural stroke rate in all high-risk patients compared with CEA and led to an additional increase in in-hospital mortality in symptomatic patients.
3.2. Impact of contralateral stenoses on CEA
The impact of contralateral stenosis and occlusion on the CEA outcome in 15,487 symptomatic and asymptomatic patients with carotid stenosis was examined based on the registry of the Vascular Study Group of New England (VSGNE) from 2003 to 2015 [10]. The study concluded that although contralateral carotid occlusion resulted in a slightly higher stroke/mortality rate in CEA, contralateral occlusion should nonetheless 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. Impact of age and gender on CEA
The impact of age and gender on CEA outcomes was examined based on the German quality assurance database [11]. A total of 142,074 procedures from 2009 to 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 gender, 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 true only to a very limited extent for the stroke risk. Although perioperative neurological complications were significantly increased 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 outcome was also reviewed based on the Society for Vascular Surgery Vascular Quality Initiative (VQI) database [12]. 7390 octogenarians and nonagenarians were compared with 35,303 younger patients. Although in the older patients perioperative neurologic complications increased significantly, in the end they were so low that age alone cannot be an exclusion criterion for CEA. However, at 93.74% versus 97.18% in the younger patients, 1-year survival was significantly less favorable.
3.4. Early carotid revascularisation by CEA
One study from 2017 examined "optimal" CEA timing after the onset of neurologic symptoms due to carotid stenosis [13]. The Vascular Study Group of New England (VSGNE) database contained 989 symptomatic patients with carotid stenosis who underwent CEA within 1 month of the neurological event. When CEA was performed less than 2 days after the onset of neurological symptoms, the rate of postoperative stroke was 7.3% versus 4.0% in the group with 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 for prevention of 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.
The Carotid Alarm Study also found an increased risk for CEA within the first 48 hours after the neurological event [14].
3.5. CAS
In 2017, the ACS NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database identified approximately 450 patients who had undergone CAS for carotid stenosis [15]. The rate of adverse postoperative events at 30 days was 7.1%. Postoperative stroke or death was observed in 3.6% of asymptomatic and 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 them the defined thresholds for postoperative death or stroke were exceeded. Older patients (>80 years), 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.
A study of 4717 elective procedures from the German quality assurance database [17] explored the relationship between the postoperative outcome of CAS and the time interval between the onset of neurological symptoms and the procedure. The study demonstrated that early CAS within the first 7 days following the neurological event was associated with an increased risk of postinterventional stroke/death.