Stroke is an important cause of death and long-term disability in humans, and more than 80% of strokes are ischemic strokes. Atherosclerotic stenosis and occlusion of the carotid arteries is one of the most common causes of ischemic stroke, and Spence was the first to use surgical treatment for carotid stenosis in 1951. In the 1980s, carotid endarterectomy (CEA) became the traditional treatment for extracranial carotid stenosis in North America and Europe. In the last 20 years, with the North American symptomatic carotid endarterectomy trial (NASCET), European carotid surgery trial (ECST) The results of several large-scale, multicenter, randomized, controlled clinical trials, including the North American symptomatic carotid endarterectomy trial (NASCET), the European carotid surgery trial (ECST), the Asymptomatic carotid atherosclerosis study (ACAS) and the Asymptomatic carotid surgery trial (ACST), have been published. The publication of the results of several large-scale, multicenter, randomized, controlled clinical trials, including the ACAS study and the Asymptomatic Carotid Surgery Trial (ACST), has further established CEA as the “gold standard” in the treatment and prevention of stroke from the perspective of evidence-based medicine [1-4]. However, with the development of endovascular techniques and the continuous improvement of interventional devices, carotid angioplasty and stenting (CAS) is becoming an effective treatment for carotid stenosis after CEA. Cheng Wei, Department of Vascular Surgery, Beijing Anzhen Hospital CAS has been controversial since its clinical application in the late 1990s, and the debate has been ongoing about the advantages and disadvantages of CEA and CAS for carotid artery stenosis. It is undoubtedly of great importance to make an objective and accurate evaluation of their safety and effectiveness. However, the only feasible way to scientifically evaluate the efficacy of CAS is to compare it with CEA and find evidence from the perspective of evidence-based medicine. A series of single-center and multicenter prospective randomized controlled studies (e.g., CAVATAS, Kentucky study, Leicester study, Wallstent study, SAPPHIRE, SPACE, and EVA-3S) published in recent years have directly compared CEA with CAS, but some contradictory results have brought about extensive controversy. In February 2010, the results of the highly anticipated randomized clinical trial of carotid revascularization endarterectomy versus stenting (Carotid Revascularization Endarterectomy vs. Trial (CREST) results were presented at the International Stroke Conference in the USA and published in the New England Journal of Medicine [6]. The CREST study provides new evidence on the choice of treatment for patients with carotid artery stenosis, whether to choose CEA or CAS, and how clinicians should decide. CEA is a classic procedure for the treatment of severe carotid artery stenosis, just as CABG once was in the treatment of coronary artery disease. So can CAS achieve the same great success as coronary intervention (PCI)? The early CAVATAS study found no significant difference in the risk of ipsilateral stroke at 3 years between CEA and CAS, which led to the conclusion that CAS was also effective. The SPACE study failed to confirm that CAS is no worse than CEA, while the EVA-3S study found a 3-fold increase in surgical risk for CAS compared with CEA. The newly published ICSS interim safety analysis also suggests that CAS is significantly riskier than CEA [5]. Existing guidelines also recommend CEA as the treatment of choice for symptomatic carotid artery stenosis [11]. Therefore, can the CREST study with the composite endpoint of stroke, myocardial infarction, death, and ipsilateral stroke at 4 years of follow-up show equivalence between CAS and CEA treatment? This is a matter of great concern to clinicians. The CREST study showed no significant difference in the primary composite endpoint (stroke, myocardial infarction, or death) between CAS and CEA in symptomatic or asymptomatic men or women with carotid stenosis. In the perioperative period, the CAS group had a higher risk of stroke, whereas the CEA group had a higher risk of myocardial infarction. Compared with previous clinical studies, the choice of composite endpoint is clearly a very important issue. Unlike CREST, the EVA-3S and SPACE studies used stroke and death as composite endpoints at 30 d postoperatively, and the EVA-3S study was terminated early because stroke and mortality were significantly higher in the CAS group than in the CEA group at 1 month and 6 months postoperatively. The newly published ICSS midterm safety analysis with stroke, death and myocardial infarction at 120 d as composite endpoints showed significantly higher stroke and mortality in the CAS group than in the CEA group, while the incidence of myocardial infarction remained similarly low in both groups, clearly demonstrating the advantage of CEA over CAS. The timing of the composite endpoints is another important factor; the primary composite endpoints of the CREST study were perioperative stroke, myocardial infarction, all-cause death, or ipsilateral stroke within 4 years of follow-up; the EVA-3S and SPACE studies both used 30 days postoperatively as the endpoint, and the ICSS reported an interim analysis of the endpoint event at 120 days, leaving a longer follow-up period to be analyzed. Therefore, the CREST study is more rigorous and convincing in terms of the selection of the primary composite endpoint content and time. 2. In the CREST study, the increased stroke and mortality in the CAS group were offset by a reduced rate of myocardial infarction: however, the debate is whether perioperative stroke and myocardial infarction are equivalent in terms of their impact on patients’ long-term health. (1) Stroke is an unavoidable problem in CAS. Although an absolute majority (96.1%) of the CREST studies used thromboprophylactic devices, they did not lead to a reduction in stroke and mortality compared with CEA. The overall disadvantage of CAS in completed controlled trials stems primarily from the onset of postoperative minor strokes, with almost every study confirming a high incidence of minor strokes in CAS. In the CREST study, the incidence of postoperative minor strokes was twice as high in CAS (2.9%) as in CEA (1.4%). In the ICSS study, the incidence of minor strokes was 4.1% (CEA) and 7.7% (CAS), respectively; in particular, in the subgroup analysis, magnetic resonance-weighted imaging was used to monitor new infarcts, and the rate of new infarcts at 3 days postoperatively was found to be 50% and 17% in the CAS and CEA groups, respectively, i.e., three times higher in the CAS group than in the CEA group. (2) The incidence of myocardial infarction is also a problem that cannot be avoided by CEA. Several clinical trials have shown a high incidence of myocardial infarction after CEA, probably because: (1) CEA is more traumatic than CAS; (2) CAS is followed by long-term combined aspirin and clobetasol, while CEA is followed by one of these drugs alone for a short period of time. Therefore, even in patients undergoing CEA, more consideration should be given to the possibility of multiple vascular lesions, and preoperative and postoperative attention should be paid to cardiac events. Another interesting result of the CREST study is the relationship between age and efficacy. cas tends to be more effective in patients under 70 years of age, whereas CEA is more appropriate in patients over 70 years of age. Similar results were seen in the earlier SPACE study. suggesting that older patients require a more demanding stent placement technique, as the degree of atherosclerosis, calcification, and vascular tortuosity may be more severe in older patients. In conclusion, the CREST study is one of the largest clinical studies on CAS. The breakthroughs and innovations of this study are: (i) the inclusion of myocardial infarction as the primary endpoint; (ii) the first randomized controlled trial including both symptomatic and asymptomatic patients; (iii) the participation of experienced interventionalists and surgeons; and (iv) the mandatory use of thromboprophylactic devices. The results showed similar net clinical benefits for CAS and CEA and reaffirmed the value of thrombectomy devices and the importance of interventionalist skills training. Stroke and mortality were lower in both CAS and CEA groups compared with previous clinical trials. A recent meta-analysis of 11 randomized clinical trials (not including the CREST study) [12] showed that the near-term effects (rather than the long-term effects) were dominant for CEA compared with CAS. However, we need more long-term outcomes to further judge the relative riskiness of the two; similarly, more information is expected to clarify the relationship between age and outcome, which in turn will help in the selection of the procedure for younger patients. Treatment strategy for carotid stenosis: CEA or CAS? As the standard of living improves and the population ages, the incidence of carotid stenosis is bound to increase year by year, and the number of patients requiring treatment will also increase. Therefore, the choice of treatment for carotid artery stenosis – CEA or CAS – is a decision that clinicians must make. CEA, the traditional treatment for this disease, can completely eradicate the lesion and should be considered the gold standard for the treatment of carotid stenosis. CAS is a new technique with the main advantages of being minimally invasive, having fewer complications, and allowing simultaneous treatment of lesions at different sites, including external carotid artery, internal carotid artery, and cranial artery stenosis. Numerous clinical trial studies have demonstrated the advantages and disadvantages of both CEA and CAS. Therefore, for a patient with carotid artery stenosis, CEA or CAS should be considered in the following aspects. Despite the encouraging results of the CREST study, existing guidelines still recommend CAS as a complementary measure to CEA. (1) 2006 ACC/ASA guidelines [11]: (1) If TIA/ischemic stroke with ipsilateral extracranial carotid stenosis of 70% to 99% occurred in the last 6 months, CEA is recommended by physicians with morbidity and mortality <6% (Class I recommendation, level of evidence A); if TIA/ischemic stroke with carotid stenosis of 50% to 69% occurred recently, the decision is based on the patient's age, gender, comorbidity and The decision to perform CEA is based on the severity of the initial symptoms (Class I recommendation, Level of Evidence A); carotid stenosis <50%, no CEA (Class III recommendation, Level of Evidence A). (ii) CAS may be considered for symptomatic, carotid stenosis >70%, and patient conditions that make CEA inappropriate, such as contraindication to surgery, restenosis after CEA, or radiological carotid stenosis (Class IIb recommendation, Level of Evidence B). (3) CAS should be done by interventionalists with morbidity and mortality of 4% to 6% (Class IIa recommendation, Level of Evidence B). (2) Guidelines for the management of ischemic stroke and transient ischemic attack published by the Executive Committee of the European Stroke Organization (ESO) (2008) [13]: (1) Primary prevention: CEA is not recommended for asymptomatic individuals with significant carotid stenosis, except in those at high risk of stroke (Class I evidence, Level C recommendation). CAS is not recommended in asymptomatic patients with carotid stenosis (Class IV evidence, good clinical practice). (ii) Secondary prevention: CEA is recommended in patients with 70% to 99% stenosis (Class I evidence, Level A recommendation); CEA should only be performed in medical centers with a perioperative complication (all strokes and deaths) rate of less than 6% (Class I evidence, Level A recommendation); CEA may be considered in some patients with 50% to 69% stenosis; CEA in 50% to 69% stenosis should only be performed in patients with a perioperative complication (all strokes and deaths) (Class I evidence, Level A recommendation). Complications (all strokes and deaths) occurring in less than 3% of medical centers (Class I evidence, Level A recommendation). CEA is not recommended for patients with less than 50% stenosis (Class I, Level A recommendation). CAS is recommended only for patients with severe symptomatic carotid stenosis who have a contraindication to CEA, stenosis at a site inaccessible to surgery, restenosis after early CEA, radiographic stenosis (Class IV evidence, excellent clinical practice). However, it is debatable whether the recommendations of the above guidelines are fully adapted to our national situation, because there are relatively few established CEA physicians and centers in China, while CAS is relatively mature, and the guidelines do not recommend CEA for centers or patients with perioperative complications of more than 3% to 6%. 2. Comprehensive evaluation and tailor-made assessment Reviewing the years of controversy between CEA and CAS, no final conclusion has been obtained so far. However, CAS has finally grown through years of clinical trials, and more than a decade ago, controlled studies were repeatedly terminated because of the high number of adverse events associated with CAS; more than a decade later, CAS has shown a tendency to partially replace CEA. In addition, after more than a dozen clinical trials, the focus of clinicians has shifted from which modality is the best treatment to which patients are suitable for which modality. In particular, the publication of the CREST study results has provided clinicians with more objective evidence regarding treatment modality selection. Christopher White, President of the Society for Cardiovascular Angiography and Interventions (SCAI), commented: “The significance of the CREST study is clear for patients at high risk of stroke, as early CAS was used as an alternative treatment for patients who were not candidates for CEA, and based on the results of the latest study, internists have more effective individualized treatments for patients at high risk of stroke. Steven Bailey, executive chairman, commented: “Stroke is the third leading cause of death in the United States, and the results of the CREST study are valuable and encouraging, as internists now have two equivalent treatment options for patients at risk for stroke. Although the results of the CREST study are encouraging, many questions remain: (1) Can CAS be recommended for all patients with carotid artery stenosis? CAS and CEA have their own anatomic contraindications; CREST showed differences in efficacy between patients with onset <6 months and <14 days; CAS or CEA in symptomatic patients in the acute phase or in patients >80 years of age is associated with worse perioperative outcomes, and the risk-benefit ratio of the intervention remains to be evaluated. The risk-benefit ratio of the intervention has yet to be evaluated. Therefore, when deciding on a treatment modality for a patient, the clinician should assess the patient’s benefit and risk in a comprehensive manner to truly “tailor” the treatment. For example, in young patients, patients with moderate to severe stenosis and patients at high risk for CEA, CAS is no less safe and effective, and has shown great advantages of being minimally invasive, so CAS should be recommended. 3. Enhance training and standardize treatment CAS was gradually developed through years of clinical practice. Although the inherent disadvantages of CAS have been confirmed by controlled clinical studies, unlike coronary vessels, endovascular treatment of carotid arteries may produce more opportunities for embolization and thus perioperative stroke events. The results of the CREST study showed that stroke and mortality rates were still higher in the CAS group than in the CEA group, but were lower in both groups compared with previous clinical trials. This result is mainly due to the training, certification and audit of the operators. From the beginning of the CEA and CAS controlled trials to today’s CREST study, the qualifications of participating centers and operating physicians have been increasingly important, and both SAPPHIRE and EVA-3S have been biased by the lack of experience of the physicians. The study was even based on similar qualification, with a pre-test of more than 1,500 treatment cases specifically, closely monitoring and promptly terminating centers or surgeons with high complication rates. Compared to the mature CEA technique, CAS has been greatly developed through several controlled clinical trials, with progressively lower adverse event rates of 11.9%, 9.6%, 6.92% and 4.1% for the SAPPHIRE, EVA-3S, SPACE and CREST studies, respectively. And the experience of the CREST study shows that adequate training, monitoring and quality control, standardized devices and techniques are essential. In conclusion, it is indisputable that the use of CAS is gradually increasing with the advancement of CAS techniques and devices. Dr Manesh Patel of Duke University made a statistic that from January 1, 2003 to December 31, 2006, a total of 320,354 CEAs were performed throughout the United States, and the surgery rate decreased from 3.2 per 1,000 to 2.6 per 1,000 per year; 19,444 CASs were performed. The procedure rate increased from 0.3 per 1000 to 0.4 per 1000. However, there was no increase in the overall carotid revascularization rate. There is no convincing evidence that CAS can replace CEA, and the choice of treatment modality is inconclusive. Until more evidence becomes available, CEA remains the treatment of choice for the vast majority of patients with symptomatic carotid stenosis, and treatment of asymptomatic patients remains controversial. Due to the lack of long term observational data, individualized treatment may be the most appropriate option. However, regardless of the chosen modality, treatment of carotid stenosis should be based on adequate knowledge of pharmacotherapy; evaluation of collateral circulation and cerebral hemodynamics; analysis of cerebral angiography; and understanding of the overall treatment strategy and the use of standardized treatment protocols. It is our goal to select the most appropriate treatment for each patient in order to improve the quality of life and prognosis of the patient and to reduce the incidence of ischemic stroke and the disability rate.