Carotid endarterectomy (CEA), which emerged in the 1950s, surgically solved the problem of arterial stenosis with better results than drug treatment alone, but had disadvantages such as high trauma and slow recovery.
Endovascular intervention (CAS) for cerebral stenosis began in the 1980s and has been increasingly recognized by physicians and patients for its advantages of less trauma, less patient pain, and shorter hospital stays. However, comparative studies of the efficacy and safety of CEA versus CAS have been the darling of major clinical research centers worldwide, and the results of the studies have been the subject of debate in various academic conferences. The following is a brief overview of those between CEA and CAS.
Atherosclerotic stenosis of the carotid artery is an important cause of ischemic stroke, accounting for about 15% to 20% of all ischemic stroke causes. The degree to which carotid stenosis leads to an increased risk of ischemic stroke is directly related to the severity of the stenosis and the presence or absence of symptoms. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) showed that in patients with severe carotid stenosis (≥70% stenosis), the recurrence rate of stroke was 26% at 2 years even with optimal pharmacologic therapy; and CEA CEA can reduce the incidence of stroke to 9% at 2 years after surgery, which is significantly better than the best medical treatment.
CEA is now a safe and effective standard procedure for the treatment of carotid artery stenosis or occlusion. The efficacy of CAS compared with CEA as the standard procedure for carotid artery stenosis has been a hot topic of research in cerebrovascular disease in recent years. To this end, several multicenter randomized controlled studies have been conducted internationally.
The Carotid and Vertelral Artery Transluminal Angioplasty Study (CAVATAS) in 2001 was the first multicenter randomized controlled trial to compare the advantages and disadvantages of CAS versus CEA. The trial randomized 504 patients from 24 centers, with 251 in the CAS group (26% stented, 74% ballooned, and no intraoperative brain protection device) and 253 in the CEA group. The difference in the incidence of stroke or death between CAS and CEA at 30 d postoperatively was not statistically significant (10.0% vs 9.9%). the incidence of ipsilateral stroke at 3-year follow-up was also not significantly different between the two groups.
The Stenting and Angioplasty with Protection in Patients at High Risk for CEA study (The Stenting and Angioplasty with Protection in Patients at High
Risk for Endarterectomy, SAPPHIRE) is the first prospective multicenter randomized controlled trial comparing CEA with CAS under cerebral protection, enrolling 334 patients from 29 centers. The results showed that the 1-year incidence of serious adverse events with angioplasty with protection was 12.2% compared to 20.1% with surgery, and that angioplasty had better outcomes than surgery for all endpoint events (death: 6.9% vs. 12.6%, stroke: 5.7% vs. 7.3%.
myocardial infarction: 2.5% vs. 7.9%). Based on these data, carotid stents with distal protection devices were approved by the US Food and Drug Administration in 2005 for use in symptomatic patients with ≥50% carotid stenosis and asymptomatic patients with ≥80% stenosis.
The Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy trial (Stent-Supported Percutaneous
Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) was designed to demonstrate that CAS in low-risk, symptomatic patients with >50% stenosis of the internal carotid artery is not inferior to CEA. 1200 patients from 35 centers were included, and 27% of CAS patients had a Brain protection devices were used in 27% of patients with CAS; the 30-d postoperative stroke or death rate was 6.84% in the CAS group and 6.34% in the CEA group, with no statistically significant difference between the two groups.
At midterm follow-up of SPACE, the incidence of perioperative stroke and death and ipsilateral ischemic stroke within 2 years was 8.8% in the CEA group. The interim results of SPACE suggest that the risk of stroke is low and very similar in both CEA and CAS if patients are treated successfully and without complications.
The Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial (The Endarterectomy Versus Angioplasty in Patients with Severe Carotid Stenosis trial).
Angioplasty in patients with Severe Symptomatic carotid Stenosis (EVA-3S) was discontinued early because of a 2.5-fold increased risk of stroke and death in the CAS group. Notably, the incidence of stroke in the stent group of this trial was even higher than in other previous trials of carotid interventions without stents or distal protection devices, and the high rate of complications in the stent group may be due to the lack of experience of the surgeon with carotid manipulation and distal protection devices.
In addition, the pharmacological regimen of patients in the stent group was poor, with 83% and 85% receiving dual antiplatelet therapy preoperatively and postoperatively, respectively, contrary to the standard requirement of dual antiplatelet therapy from 3-5 d preoperatively to at least 30 d postoperatively. The lower and similar risk of ipsilateral stroke after the perioperative period in the CAS and CEA groups at the subsequent 4-year follow-up (4.49% and 4.94%, respectively) also illustrates the influence of CAS operator experience and perioperative medication management on the trial results.
In view of this, the European Society for Vascular Surgery published guidelines on indications and techniques for the invasive treatment of carotid stenosis in 2009, recommending that: (i) in symptomatic patients, surgery is currently the best treatment option (Class A recommendation); (ii) successful CAS has a similar effect on stroke prevention in the medium term as CEA (Class A recommendation); and (iii) in asymptomatic patients or symptomatic patients at high risk of CEA surgery CAS should be administered in large centers with a low incidence of perioperative stroke and death or in well-designed clinical trials (Class C recommendation).
Because of the shortcomings of previous studies in terms of unscientific trial design, varying operator qualifications, or inconsistent use of interventional materials, the National Institutes of Health initiated a multicenter randomized controlled trial, the Carotid Endarterectomy and Stent Reconstruction Trial (CREST), in 2000 to compare carotid endarterectomy with stent revascularization. distal protection of carotid stenting in symptomatic patients with ≥50% stenosis versus asymptomatic patients with ≥70% stenosis. The trial was rigorously selected from experienced trial centers with enhanced quality control and required that all patients in the stent group use the same distal protection device and self-expanding stent (Accu-net, Acculink, Guidant).
The results of the trial were published online in the New England Journal of Medicine in May 2010. The trial included 2502 patients with or without symptomatic partial carotid stenosis with a median follow-up of 2.5 years. the difference in the incidence of the primary composite endpoint events (stroke, infarction, perioperative death, and ipsilateral stroke) between the CAS and CEA groups was not statistically significant, at 7.2% and 6.8%, respectively (p=0.51). The differences in the primary endpoint events of sex and presence of symptoms were not statistically significant between the two groups. 4-year stroke and mortality rates were 6.4% for CAS and 4.7% for CEA, P=0.03; of these, 8.0% and 6.4% were in symptomatic patients (P=0.14) and 4.5% and 2.7% in asymptomatic patients (P=0.07), respectively.
During the perioperative period, the incidence of stroke was significantly higher in the CAS group than in the CEA group (4.1% vs 2.3%, P=0.01), but the incidence of myocardial infarction was lower than in the CEA group (1.1% vs 2.3%, P=0.03), and mortality was similar (0.7% vs 0.3%, P=0.18). After the perioperative period, the incidence of ipsilateral stroke was lower in both the CAS and CEA groups (2.0% vs 2.4%, P=0.85). The trial showed that although the risk differed in the perioperative period, with a higher incidence of stroke in the CAS group and a higher incidence of myocardial infarction and cranial nerve injury in the CEA group; the risk of the primary composite endpoint events (stroke, myocardial infarction, and death) did not differ between patients in the CAS and CEA groups, regardless of the presence or absence of symptoms in patients with carotid stenosis.
The results of the CREST trial will have a profound impact on the treatment of carotid artery stenosis, and upcoming guidelines may be revised as a result.
Research on interventional treatment of carotid artery stenosis is a hot topic and focus in the field of cerebrovascular disease, with two studies on Optimal Medical Therapy (OMT), CE
Two randomized controlled trials comparing the efficacy of Optimal Medical Therapy (OMT), CEA, and CAS are of interest: the SPACE-2 study, which compared current OMT, CAS, and CEA in patients with asymptomatic carotid stenosis; and the Transatlantic Asymptomatic Carotid Intervention Trial (TACIT). Another is the Transatlantic Asymptomatic Carotid Intervention Trial (TACIT): a comparison of OMT + CAS or CEA versus OMT alone for stroke and death prevention in patients with asymptomatic carotid stenosis.
Perspectives on Carotid Stenosis
The efficacy of CEA for carotid stenosis has been confirmed by nearly 50 years of clinical practice and several multicenter randomized controlled trials, and has been widely performed in western developed countries, but the implementation of endarterectomy in China is very limited for various reasons, which is far from the needs of the large number of patients with ischemic cerebrovascular disease in China. Therefore, interventional treatment of carotid artery stenosis has shown a broader application in China.
Many randomized controlled trials comparing the efficacy of CEA and CAS in recent years, especially the results of the CREST trial published this year, have also confirmed the role of CAS in carotid artery stenosis. With the continuous improvement of the stenting process, the widespread use of distal embolic protection devices and the increasing experience of operators, we have reasons to believe that interventional therapy will emerge as an indispensable treatment option in the treatment of carotid stenosis (optimal drug therapy, carotid endarterectomy and interventional therapy).