Procedural and mid-term outcomes of carotid artery stenting and carotid endarterectomy in asymptomatıc patients: A single center experience

Amac: Aterosklerotik Karotid Arter Stenozu (CS) tum inmelerin %20’sinden sorumludur. Asemptomatik CS yonetimi daha belirsizdir. Hastaya ozel tedavi icin, Karotis Endarterektomi (KEA) isleminin daha riskli oldugu durumlarda, cerrahlar ayrica karotis arter stentlemesi (KAS) yapabilecek tecrube ve kapasitede olmalidir. Bu calismada, tum islemleri (KAS ve KEA) ayni cerrah yapmis ve tek tip stent ve emboli koruma araci kullanilmistir. Ayrica, prosedur sirasindaki monitorizasyon 24 saate yayilmistir. Bu calismanin amaci, ayni operator tarafindan 1 yilda KAS veya KEA uygulanan asemptomatik CS hastalarinin islem ve takip sonuclarini karsilastirmaktir. Gerec ve Yontemler: Internal karotid arter ciddi okluzyonu nedeniyle klinik ve anatomik risk profillerine gore, 1.Ocak.2018-31.Aralik 2018 tarihleri arasinda Ankara Numune Egitim ve Arastirma Hastanesi Kalp-Damar Cerrahi Kliniginde KAS (Grup 1, n=17) veya KEA (Grup 2, n=18) uygulanan asemptomatik hastalarin retrospektif incelemesi yapildi. Doppler Ultrason ve norolojik degerlendirme hastalar isleme alinmadan, taburcu olmadan, prosedur sonrasi 30.gun, 6.ay ve 1.yilda yapildi. Hastalarin demografik ve klinik ozellikleri, anjiyografik degiskenleri, islem sonrasi 30 gun boyunca olum, inme ve miyokard enfarktusu ve 1 yillik ipsilateral inme oranlari karsilastirildi. Teknik basari, prosedur basarisi, birincil aciklik , klinik basarisizlik, islem sirasinda yardimci manevralari iceren diger birincil sonlanim noktalari ve komplikasyonlar, 12 ayda klinik olarak yonlendirilen hedef lezyon revaskularizasyonundan kurtulma, olumden kurtulma, tum felclerden kurtulma ve restenoz oranlarindan kurtulma oranlarini iceren ikincil sonlanim noktalari degerlendirildi ve gruplar arasinda karsilastirildi. Bulgular: Sekiz hastada (47.0%) yuksek riskli anatomik kriter ve 11 hastada (%64.7) yuksek riskli klinik kriterler mevcuttu. Grup 2’deki hastalar daha yasli (67.7±7.4 vs 71.2± 6.9, p<0.05) idi, ancak hiperlipidemi (58.8% vs 44.4%, p<0.05), hemodiyaliz gerektiren kronik bobrek yetmezligi (11.7% vs 0.0%, p<0.05) ve sol ventrikul disfonksiyonu (17.6% vs 0.0%, p<0.05) sikligi Grup 1’de fazlaydi. Grup 1’deki hastalarin CCDS skoru Grup 2’ye gore dusuktu (4.7 ± 1.3 vs 7.3 ± 1.2; p<0.05). CEA yapilan hastalarin lezyonlari daha uzun (12.7 ± 2.6 vs 18.5 ± 4.2 mm.; p<0.05) ve daha kalsifikti (11.7% vs 50.0%, p<0.05). Benzer sekilde, grup 2’de damardaki darlik derecesi grup 1’e gore yuksek bulundu (81.4 ± 4.2 vs 88.3±6.4 %; p<0.05). Primer teknik basari her iki grup icin de %100 idi. Prosedurel klinik basari Grup 1 icin %100, Grup 2 icin %94.4 idi. Primer patens oranlari grup 1 icin 1/6/12. aylarda 100%/ 94.1%/94.1%, grup 2 icin 100%/100%/94.4%. restenozdan ve klinik olarak yonlendirilen hedef lezyon revaskularizasyondan kurtulma oranlari grup 1 icin %94.1, grup 2 icin %94.4 idi. Hicbir hastada olum, major inme, miyokard infarktusu ve sistemik komplikasyon gerceklesmedi. Sonuc: Bu calisma, onemli karotis hastaligi olan asemptomatik hastalarda KEA ve KAS icin benzer kisa ve orta donem sonuclari gostermistir. Hem KEA hem de KAS icin iyi sonuclar gostersek de, KAS acik cerrahi icin uygun olmayan vakalarla sinirli olmali ve az risk faktoru ve uzun yasam beklentisi olan hastalar icin asemptomatik karotid arter hastaliginin KEA ile tedavisi dusunulmelidir. Hem KEA hem de KAS asemptomatik hastalarda uzun sureli inme riskini azaltir. Uygun tedavi stratejisi, hastanin bireysel risk faktorlerine ve goruntuleme verilerine gore secilmelidir.


Introduction
Approximately 6.5 million strokes occur per year. [1] Stroke is the second leading cause of death and is the leading cause of premature mortality and morbidity for both men and women. [2,3] Atherosclerotic carotid artery stenosis (CS) is responsible for ~20% of strokes. [4,5] Patients with vascular disease and risk factors such as diabetes mellitus (DM), hypertension, hyperlipidemia, and smoking are at significantly higher risk of developing carotid artery atherosclerosis. Not all patients with carotid atherosclerosis are at increased risk of stroke; however, a strong association between the severity of stenosis and stroke risk still exists. The prevalence of severe asymptomatic CS is as high as 3.1% . [6] CS refers to a >50% stenosis of the extracranial internal carotid artery (ICA), with stenosis severity estimated using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. [7] Of all strokes, 10-15% occurs due to thromboembolism that stems from a 50-99% ICA stenosis. [8] CS is defined as 'symptomatic' if associated with symptoms in the preceding 6 months and 'asymptomatic' if no prior symptoms can be identified, or when symptoms occurred beyond 6 months. Unfortunately, carotid atherosclerosis is often asymptomatic until a disabling or fatal stroke occurs. Even when asymptomatic, stenosis of the carotid artery has been reported to place an individual at more than a 3% increased risk of having a stroke in the following year (greater than 50% increased relative risk). [9] CS often is treated with aggressive medical therapy (statins, antiplatelet and antihypertensive agents), smoking cessation, treatment of comorbidities, and surgical intervention-either carotid artery stenting (CAS) or carotid endarterectomy (CEA)and CS revascularization has conventionally been performed by CEA. CAS was developed as an alternative to CEA, and in the current era, it is a widely used procedure for carotid artery occlusive disease, especially in patients at high risk for CEA. [10] There are subtle differences in recommendations regarding CAS in symptomatic patients. Guidelines stipulate that CEA should be preferred over CAS in symptomatic patients with 70-99% CS as class Ia recommendation and with 50-69% CS as class IIa recommendation [11,12] -especially if >70 years old [13]-; and CAS as an alternative for patients who present with adverse anatomical features or medical comorbidities that are considered to make them high risk for CEA. [14] Though the risk of operative stroke/death is higher with CAS, major randomized clinical trials (RCTs) report event rates under the recommended 6% cut-off value for both treatment modalities. But as a general recognition, guidelines recommend that CEA be performed as early as possible after the neurologic symptom seen in patients with symptomatic carotid stenosis (≥50%).
On the other hand, the management of CS in an asymptomatic patient has been less clear, and there is also an ongoing debate. Since the reduction in the incidence of stroke among asymptomatic patients with established severe CS has not been shown in prospective studies with BMT, uncertainty remains regarding the optimal technique for long-term prevention of vascular events. It is clear that both CEA and CAS reduce long-term stroke risk in asymptomatic patients. With regard to periprocedural outcomes of RCTs, most recent ESVS guidelines recommend patients with an "average surgical risk", and asymptomatic CS of 60-99% should be considered for CEA and suggest CAS in asymptomatic patients who have been deemed "high risk for CEA and who have an asymptomatic 60-99% stenosis in the presence of clinical and/or imaging characteristics that may be associated with an increased risk of late ipsilateral stroke, documented perioperative stroke/death rates are <3%, and if the patient's life expectancy is >5 years as class IIa recommendation. [8] Factors that are classified as a high risk for CEA include age >80 years, clinically significant cardiac disease, severe pulmonary disease, contralateral ICA occlusion, contralateral recurrent laryngeal nerve injury, previous radical neck surgery or radiotherapy, in situ tracheotomy, severe cervical spine arthritis, surgically inaccessible carotid stenosis. [15] A relative contraindication to CAS is octogenarians, where high complication rates have been reported from several trials. [16] Potential advantages include avoidance of general anesthesia, avoidance of an incision in the neck with the risk of cranial and cutaneous nerve damage, and a reduction in the rate of general complications of the surgery, for example, myocardial infarction. However, CAS does not remove the atherosclerotic lesion and may dislodge emboli during catheterization, causing the periprocedural stroke. We know that the risk of the permanent  neurological deficit because of diagnostic cerebral angiography alone is considerable and estimated to be about 1%. [17] Percutaneous transluminal angioplasty (PTA) is a critical component of CAS procedures and carries significant embolic risk. [18] Its use before or after stent deployment is being scrutinized.
Concern regarding the risk of distal embolization of debris being dislodged from the atheromatous plaque during stent deployment and resulting in neurological deficit has led to the introduction and increasing use of cerebral embolic protection devices (EPD), but evidence on protection devices used during CAS is scarce since a small amount of randomized evidence comparing the different cerebral protection systems exists. [1] However, ESVS guidelines' class of recommendation for the use of EPDs in patients undergoing CAS is defined as class IIa. [8] The local anatomic and lesion factors increase the fluoroscopy time and risks associated with CAS [19] whereas systemic factors and comorbidities increase the risks associated with CEA.
The main aim of treating CS is the prevention of stroke in the long term. CEA is effective at preventing ipsilateral stroke over long-term follow-up periods of 10 years or longer. [20] To provide an alternative, CAS needs to have similar long-term effectiveness, but in situations were CEA is thought to be more risky, surgeons must also have enough experience and capability to perform CAS to provide suitable, patient-tailored treatment, should not choose the one which the operator is experienced. Better selection of high-risk surgical patients or high-risk CAS patients is critical in providing the best therapy for each individual patient. In this study, the same operator performed all interventions (CAS and CEA), and one type of stenting device and EPD was used. In addition, periprocedural monitoring was carried out for at least 24 h. The objective of this study was to compare procedural results and 12-month follow-up outcomes of asymptomatic patients who were treated by the same operator-either CAS or CEA-in one year.

Study Design and Patient Population
A retrospective single-center review involving asymptomatic patients with severe stenosis of the ICA caused by atheroscle-rotic disease who was treated with either stenting with embolic protection (Group 1, n=17) or carotid endarterectomy (group 2, n=18) between 1 January 2018 and 31 December 2018 at Numune Research and Training Hospital, Department of Cardiovascular Surgery, Ankara-Turkey was conducted.
The study was approved by the regional ethics committee at Başkent University. Procedural data were prospectively recorded; data on complications were retrospectively recorded from the computerized chart. Informed consent was obtained from all the patients participating in the study.
Patients were recruited in clinical practices and referred for possible revascularization of known or suspected CS; they were then screened for eligibility on the basis of findings from duplex ultrasonography. Before enrollment, a neurologist confirmed each patient's asymptomatic status (defined as having been free, in the ipsilateral hemisphere, from stroke, transient ischemic attack, and amaurosis fugax for 180 days before enrollment).

Planning
In order to compliment treatment strategy towards individual patients, primary interest has been developed in identifying whether any carotid lesion characteristics place a patient at high risk for operative stroke with CAS or CEA. Various lesion-related and procedure-related risk factors have been described, which may increase the CAS-related risk of operative stroke and high surgical risk for CEA, many of which have been identified on secondary analyses of major RCTs. The formal decision for the type of treatment was taken by the surgeon. Only patients with an asymptomatic 60-99% stenosis according to NASCET criteria, which may be associated with an increased risk of late ipsilateral stroke, were recruited in the study. Those patients who were eligible and carried high surgical risk for CEA [8] was operated via CAS (Group 1), whereas patients who had "average surgical risk" and criteria associated with increased difficulty for CAS was operated by CEA. The criteria were previously described and were similar to the criteria for other registries and ESVS guidelines. [8,[21][22][23][24] Enrollment criteria were shown in table 1.
Furthermore, operator characteristics which had reported to in-  year) in-trial case volume had 10.1% and 8.4% risk of operative stroke/death, respectively. High-volume operators (>5.6 procedures per year) like in our study, had the lowest operative stroke/death rate at 5.1%. [25] Exclusion criteria are listed in table 2 and previously described [21][22][23]26] Procedures CAS Before the procedure, all patients received aspirin (100 mg/d) and clopidogrel (75 mg/d) for at least 2 days plus a loading dose of clopidogrel (300 mg) if they had not previously been on clopidogrel. The patients still received their regular antihypertensive medications, with the exception of beta-blockers, on the morning of the procedure.
Patients are placed in a supine position; both groins are prepared routinely. The head is placed in a cradle and gently secured to decrease patient motion during critical portions of the procedure. The procedure is performed with the patient awake under local anesthesia, although minimal sedation is acceptable in particularly anxious subjects. After retrograde femoral access with a 5F sheath under US control, 1 mg/kg unfractionated heparin was administered to maintain activated clotting time >250 sec throughout the procedure. Continuous arterial pressure and electrocardiographic monitoring were performed during the procedure.
Diagnostic angiography was performed using a diagnostic catheter (5-Fr Omni Flush; Cordis, Fremont, CA, USA) including arch angiography to opacify the aortic arch and supra-aortic vessels in order to evaluate the anatomic characteristics such as lesion location, the severity of the stenosis, tortuosity of the target vessels, distance from the origin of the treated artery to the beginning of the descending aorta, the vertical distance from the top of the arch to the origin of the target vessel, angulated takeoff of the vessel (≤ 30 degrees between the aortic arch and the innominate artery [for right-sided lesions] or left CCA [for left-sided lesions]), index lesion calcification, ulceration, and eccentricity.
Following selective catheterization of the ipsilateral mid-distal common carotid artery (CCA) (typically with a Simmons II catheter), a selective arteriogram of the carotid bifurcation is performed, paying careful attention to choose a view that provides minimal overlap of the ICA and external carotid arteries (ECA) and provides maximum visualization of the target lesion. A complete cerebral arteriogram, if not performed previously, is performed as a baseline and to identify intracranial pathologies, such as aneurysms and arteriovenous communications, and to determine the patency and completeness of the circle of Willis. After selective catheterization, the diagnostic catheter and 5F sheath were removed (while maintaining constant visualization of the guidewire in the ECA during this process) and a long (70 to 90 cm, depending on patient body habitus) 6F sheath was advanced with its dilator, into the CCA. If a difficulty occurs in advancing the long-sheath into CCA, as an alternative, the long sheath can be advanced into the transverse arch over a guidewire, the dilator is removed, and an appropriate selective diagnostic catheter is advanced into the CCA. A stiff guidewire was then advanced into the ECA, then using the wire and catheter for support the sheath was advanced into the CCA. In the alternative method, care must be taken to minimize the probability of dissection or distal embolization from the junction of the aortic arch and the innominate or left CCA, because you could not use the protection of the sheath dilator. Following maintenance of the sheath access to distal CCA, the dilator and the 0.035-inch guidewire were removed and ultimately exchanged for a 0.014-inch wire. We prefer to attach the sheath sidearm to a slow, continuous infusion of the heparin-saline solution to avoid stagnation of blood in the sheath. We performed a selective angiogram of the carotid bifurcation again, for demonstrating the area of maximal stenosis, the extent of the lesion, and normal ICA and CCA above and below the lesion, and road-mapping.
The SpiderFX Embolic Protection Device (Medtronic, MN-USA) ( Figure 1) was advanced across the lesion, with the aid of roadmapping and deployed into the distal extracranial ICA, just prior to the horizontal petrous segment. The capture wire in the Spider system was not used to cross the target lesion in any procedure. We never perform predilatation before EPD deployment. Atropine (0.5 to 1.0 mg intravenously) was administered as prophylaxis against bradycardia during balloon inflation in the carotid bulb. If hypotension occurred, the patients received 2 to 3 mg dopamine and rapid administration of additional fluids. The lesion was predilated with a 3-to 5-mm angioplasty balloon (Armada, Abbott, Cal-USA). After the predilation, the balloon was removed, another bifurcation angiogram was performed through the sheath. After proper road-mapping, The Protege RX Carotid Stent System (Medtronic, MN-USA) via a 6F-delivery system compatible with 0.014'' guidewire was deployed. Although the stent was reported to have a specific release technology (EX.P.R.T.TM) essentially eliminating premature deployment or jumping, two or three stent rings were exposed and waited for 5 to 7 seconds, allowing the distal stent to become fully expanded, well-opposed, and fixed to the ICA above the lesion for safety. Subsequently, the remainder of the stent can be deployed more rapidly with little worry that it will migrate. If necessary, the lesion was post dilated with a 5-mm balloon; larger balloons are rarely necessary. No specific balloons were used for calcific lesions. Residual stenosis of 10% or so was completely acceptable; the goal was protection from embolic stroke, not necessarily a perfect angiographic result. After CAS was completed, the delivery catheter was reversed, so the opposite end was used to capture and retrieve the filter, followed by completion angiography of the carotid bulb/bifurcation and distal extracranial ICA to assure that a dissection or occlusion did not occur. (Figure 2)

CEA
Traditional endarterectomy was performed under general anesthesia with patch closure (prosthetic). As a clinic routine, we prefer standard arteriotomy and plaque elevation. We never mobilize the carotid bifurcation until the carotid arteries have been clamped to avoid the potential of embolization of atherosclerotic plaque or thrombus in the area of the critical stenosis. As carotid clamping reduces cerebral perfusion, which may cause hemodynamic brain injury, we prevented this by routinely using a temporary shunt.

Postoperative Care
A duplex ultrasound (DUS) was obtained prior to hospital discharge as a baseline index. Subsequent DUS examinations are performed at 30-days, 6 months, and 1 year thereafter. DUS, [27] was undertaken with a standardized protocol that stipulated 16 doppler waveform samples at every examination (eight samples were taken from each side of the neck: six at 1-2 cm intervals along with the CCA and ICA, one from the ECA, and one from the vertebral artery). Waveform samples were to be obtained at a 60-degree angle between the ultrasound beam and the long axis of the vessel. The highest systolic velocity measurement from each treated carotid pathway was used to identify restenosis.
The immediate neurologic assessment of the patient upon completion of the procedures was performed by the opera-tor, secondary and follow-up neurologic assessments were performed within 24 hours and in doppler follow-up days by a neurologist. Patients in group 1 continued with dual antiplatelet therapy (a daily combination of aspirin (75-100 mg) and clopidogrel (75 mg) for 1 month, then only aspirin indefinitely. Patients in group 2, received single antiplatelet therapy with either aspirin or clopidogrel (class 1A). [8]

Definitions and Study Endpoints
Asymptomatic: Patients with no neurologic symptoms referable to the cerebral hemisphere ipsilateral to the carotid stenosis or a history of previous neurologic events without subsequent event within 180 days. Patients with prior symptoms referable only to the hemisphere contralateral to the target vessel or symptoms in either hemisphere occurring 180 days or longer prior to the initial evaluation were also considered asymptomatic.
Measurements of angiographic carotid stenosis (percentage by diameter) in CTA or DSA images were standardized by NAS-CET methodology as recommended. [28] Cumulative Carotid Disease Severity Score (CCDS) [29]: a global disease severity score for the carotid lesions which categorize the grades of severity of carotid artery disease prior to CEA or CAS, including a 0 to 3 scale corresponding to absent, mild, moderate, and severe that can be obtained for each of the risk factors.
Specific anatomical factors that may affect perioperative CAS outcomes were reported, including lesion length, lesion location, severity, calcification were recorded. Lesion length was defined using the American Heart Association/American College of Cardiology classification for coronary lesions as modified by Ellis et al, (30) in which the distance from the distinct proximal to the distal shoulder of the lesion is assessed in the projection that best elongates the portion of stenosis that is >50%. Lesion location was defined at the distal common carotid artery or proximal ICA, including the bulb, or a combination of the common distal carotid and ICA (bifurcation lesion). Target site calcification was defined as no or mild calcification vs heavily calcified lesions (>50% circumferential calcification), which was based primarily on computed tomography angiography or ultrasound imaging, or both.

Primary Endpoints
The primary endpoint was the composite of death, stroke (ipsilateral or contralateral, major or minor) and myocardial infarction during the 30 days after the procedure or ipsilateral stroke during the 365 days after the procedure. Stroke or cerebrovascular accident is defined as a cerebral infarction that manifests as a sudden onset of focal neurological deficits that persist for more than 24 hours. [31] The National Institutes of Health Stroke Scale (NIHSS), which is a serial measure of the neurologic deficit on a 42-point scale across 11 categories, including paralysis, speech difficulty, and sensory and visual loss, was used to report stroke severity. [31] A minor stroke is a new neurologic event that persists for more than 24 hours but completely resolves or returns to baseline within 30 days and changes the NIHSS by 2 to 3 points. A major stroke is a new neurologic event that persists after 3 days and changes the NIHSS by at least 4 points. An ipsilateral stroke is a stroke affecting the cerebral hemisphere supplied by the treated carotid artery. TIA is defined as a temporary focal neurologic deficit that changes the NIHSS by one or more points or retinal deficits that persists for <24 hours with a return to baseline or complete resolution of the event. [32] The periprocedural occurrence of MI in 30 days of the procedure was also reported. Accepted confirmatory evidence of an MI includes the combination of either chest pain or equivalent symptoms consistent with myocardial ischemia or electrocardiographic evidence of ischemia, including new ST-segment depression or elevation >1 mm in two or more contiguous leads, plus a significant elevation of cardiac enzymes (creatine kinase-MB or troponin) to a value 2 or more times the individual clinical center's laboratory upper limit of normal. [33,34] The other primary endpoints were primary technical success, periprocedural clinical success, primary patency at 1st-6th, and 12th months, clinical failure rates. For CEA, primary technical success is defined as the successful exclusion of the carotid plaque and closure of the artery with patch and less than a 30% residual stenosis. For CAS, primary technical success defines successful access to the carotid arterial system using a remote site; successful deployment and placement of the EPD and the carotid stent excluding the entire length of the carotid lesion; patent carotid stent with normal flow and without a significant twist, kinks, or obstruction (>30% luminal stenosis or a pressure gradient >10 mm Hg) by intraoperative measurements; and successful removal of the EPD without evidence of EPD-related vascular injuries.
Periprocedural clinical success: Vascular closure or deployment of the carotid stent. The definition of clinical success for both carotid interventions includes the absence of periprocedural stroke, death and MI and ipsilateral stroke as the result of carotid stenosis-related treatment, patch or stent infection or thrombosis, failure of device integrity, including stent fracture or pseudoaneurysm formation.
Primary patency refers to patency that is obtained without the need for an additional or secondary surgical or endovascular procedure.
Clinical failure includes a failure to complete a CEA or deploy the stent at the intended location, carotid or stent thrombosis or infection, restenosis, conversion to open or endovascular repair, or death as a result of carotid stenosis or carotid arteryrelated treatment.
Periprocedural adjunctive maneuvers were classified as planned procedures or unplanned procedures. Planned procedures comprise techniques that are part of a preformulated procedural strategy, and unplanned procedures are necessary for the management of unintended complications or an otherwise unsatisfactory outcome.

Secondary Endpoints
The secondary endpoints included complications, freedom from clinically driven target-lesion revascularization at 12 months, freedom from death, freedom from all stroke and freedom from restenosis rates.
Target lesion revascularization (TLR): any surgical or percutaneous revascularization procedure involving the original target lesion site, including repeat balloon angioplasty, stenting, endarterectomy, or any other open vascular reconstruction of the treated lesion.
Restenosis: restenosis, defined as 70% or more diameter-reducing stenosis, or target-artery occlusion occurring at the ultrasound scans at 1,6 or 12 months. The <70% threshold to define high-grade restenosis is the most accepted threshold and has been used in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the Endarterectomy versus Angioplasty in Patients with Severe Symptomatic Carotid Stenosis (EVA-3S) trial. [35][36][37] Assessment of restenosis was done when the peak systolic velocity at any location within the treated internal or common carotid artery reached or exceeded 3·0 m/s. The decision to use 3·0 m/s as the definition for restenosis was also made before unblinding of the restenosis data. Several single-institution reports [38][39][40][41] support the use of 3·0 m/s or more as an appropriate threshold to identify high-grade restenosis Complications were categorized as procedure related and systemic. All complications graded as moderate (2) or severe (3) are considered major complications, and those graded as mild (1) can be considered minor complications.

Statistical Analysis
Baseline variables are summarized with the use of descriptive statistics. Continuous variables were expressed as mean, median and ± standard deviation. Categorical variables are summarized as counts, percentages (%). Categorical values between technical success, complication and revascularization rates will be evaluated by Chi-Square analysis. For time-to-event variables, Kaplan-Meier estimates were used. The power of the study calculated in this way was calculated as 0.82 in the G-Power 3.1.9 package program and the sufficient sample width was determined as 17. All statistical evaluations will be made using SPSS 25.0 software (SPSS, Chicago, Illinois) and p <0.05 will be considered statistically significant.

Patient Characteristics and High-Risk Inclusion Criteria
Baseline demographics and the lesion characteristics of the study group are shown in Table 3 and high-risk inclusion criteria characteristics is shown in Table 4. High-risk anatomical criteria were present in 8 (47.0%) patients, high-risk clinical criteria were present in 11 (64.7%) patients. Group 2 patients were older (67.7±7.4 vs 71.2± 6.9, p<0.05). Among the demographic risk factors, hyperlipidemia (58.8% vs 44.4%, p<0.05), chronic renal insufficiency requiring hemodialysis (11.7% vs 0.0%, p<0.05) and left ventricular dysfuntion (17.6% vs 0.0%, p<0.05) were significantly more frequent in Group 1.   Taking group 2 into consideration, no blood transfusion required and all operations were performed without hemodynamic instability. In one patient (with a high calcified bifurcation lesion) surgical dissection was difficult and we had to mobilize the bifurcation before clamping. Mean duration of the operation for CEA was 62.3 ± 12.1 minutes.
All patients stayed in intensive care unit for 24 hours under continous monitorization. No patients experienced, major stroke, myocardial infarction, or death. In one patient in group 2 (the same patient whose dissection was difficult), facial numbness due to frontal lobe minor stroke was seen. It did not cause any neurological disability and resolved after 2 months. As a result, periprocedural clinical success was 100% for Group 1, and 94.4% for group 2 (p>0.05).
Other non-neurological events included vasovagal reactions in 5 patients (Group 1: two patients (11.7%) vs Group 2: three patients (16.6%); p>0.05), all treated succesfully by administration of intravenous fluids and atropine, and in one patient dopamine.

Follow-up
In-stent restenosis was diagnosed in two patients as one of them from group 1 at 6th month control follow-up, and the other patient from group 2 at 12th month control follow-up, both treated succesfully by baloon angioplasty. Primary pa-  in group 2 was more stenotic and the CCDS was increased. But the number of patients included in our trial was too small to permit conclusions with regard to the relative benefit of each technique or prediction of stroke, however in 12-months, a minor stroke was diagnosed in one patient in the CEA group after the procedure. Accordingly, there have been increasing calls to lower the acceptable stroke/death thresholds set by many guidelines as <3% for asymptomatic group. In CREST and ACT1, which mandated EPD use, 30-day stroke/death rates of 2.5% and 2.9% were reported, respectively [47,55], and are acceptable based on current guidelines. Our major stroke rate was 0%, minor stroke rate was 2.85%. in this study no strokes occured in 12-month follow up . This might be due to the combination of our small sample size, the wide use of statins (100%), and a strict protocol for patient selection.
As an other conflict, Mukherjee D. and Roffi M claimed that randomized trials did not demonstrate a significant difference between CAS and CEA in terms of procedure-related major strokes, and the statistical difference was actually related to the high association of CAS with minor strokes. [64] The best results within RCTs were seen in the CREST and ACT-1trials, where cerebral protection was mandatory and CAS practitioners were trained in its use. [47,55] In contrast, the SPACE trial observed lower ipsilateral stroke rates in CAS patients without EPD (6.2%) vs. with EPD (8.3%). [36] Although EPDs have been widely accepted as necessary adjuncts during CAS and the risk of stroke in this study is similar to the risks reported in other high-risk registries, it is important to em-phasize that strokes may occur despite the use of EPDs and failures may be due to the inability to deliver the device, device-induced complications such as vessel dissection, and incomplete capture or retrieval of debris leading to acute stroke.
We observed grossly visible debris in 41.1% of the patients and in one of them we had difficulty recovering the filter. We claim that the clustering of strokes after prolonged and complex in- Since the lesion severity for each type of intervention need to be reported to assess periprocedural risk and precise classification methodology for reporting lesion characteristics affecting outcomes have not been defined and universally accepted; we decided to use CDSS system which allows the calculation of a global disease severity score for the carotid lesion before CEA or CAS. In our study, CDSS of group 1 was significantly lower than group 2, as lesions which were more calcified, longer and stenotic were preferred to be treayed with CEA.
On the other hand, extended neck surgery has been shown to significantly increase the complexity of surgical intervention resulting in a higher risk of cranial nerve injury as well as more challenging dissection when compared to de novo open carotid intervention. Radiation into the cervical region has been shown to have various effects on the extent of fibrosis scarring as well as injury to the carotid artery itself. [29] Contralateral carotid stenosis or occlusion has traditionally been considered a predictor for adverse outcome after CEA according to NASCET data. [28] The location of the lesion relative to the carotid bifurcation and the base of the skull are anatomic variables that may increase the complexity of CEA. Those previously described anatomical factors,as well as the clinical criteria that had been reported to increase the risk after CEA formed the high-risk inclusion criteria for CAS. After detailed investigation of the literature, we developed an algorithm for enrolling the patients -evaluating risksto the groups and providing a patient-tailored treatment.
Moreover, there are studies in the literature that pointed out the risk about CAS was procedure dependent; not clinial. [82] The same group also did not find any significant difference in the risk of MI between the two procedures.
Prior studies of carotid revascularization procedures estimate 30-day re-admission rates at a range of 4.2% to 11.1% . [82,83] In our study, 30-day re-admission rate was 2.85%. ACT trial had suggested that CAS was not inferior to CEA in asymptomatic patients in terms of readmission. [47] Dakour A et al, collected data from 700 hospitals and after evaluating 95,687 patients they concluded that 30-day all-cause readmission rates were lower with CAS than CEA. [84] In initial studies comparing CEA to CAS, rates of MI were <1% for both procedures, likely because cardiac biomarkers were not measured routinely (BE- 36,37,38). The high-risk SAPPHIRE trial, which systematically collected cardiac biomarkers, was the exception, reporting MI rates of 5.9% for CEA and 2.4% for CAS (46). In the average-risk group studied in CREST, the incidence of MI after CAS was 1.7%; 3.4% with CEA under general anaesthesia; and 1.8% with CEA under locoregional anaesthesia. [85] It was also reported that any type of perioperative stroke was associated with a threefold poorer long-term survival, similar to the poorer 4-year survival observed in patients suffering a perioperative MI. [8] MI was found more associated with CEA, likely due to the periprocedural anaesthetic risk, as are cranial nerve injuries (CNI) and haematomas (although many CNIs are non-permanent). [5] In CREST, the rate of cranial nerve injury for CEA was 4.6%. [55] However, 34% of deficits had resolved at

Study Limitations
First, this is a retrospective observational study. Therefore, only associations but not causal relationships can be derived from the data. Another limitation of the study was that the data were self-reported by the operator performing the procedure. The number of patients included in our trial was too small to permit precise conclusions with regard to the relative benefit of each technique.

Conclusion
This study showed similar short and mid-term results for CEA and CAS in asymptomatic patients with significant carotid disease. CAS is a maturing procedure and has improved significantly over the past several years with the addition of protec-