Long-term cognitive and neurovascular changes after carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) has been associated with both cognitive decline and improvement, but the underlying neurovascular mechanisms are unclear. The aim of this study was to investigate the relationship between neurovascular indices and cognitive changes after CEA. METHODS: We studied 55 patients with severe (≥70%) symptomatic or asymptomatic carotid stenosis before and six months after CEA. A wide array of neuropsychological tests was arranged in eight cognitive domains and cognitive functions specific to hemisphere ipsilateral to operation. Differences in cognitive performance between patients and 38 matching healthy controls were studied with linear mixed models. Neurovascular functioning and microembolic signals were assessed with transcranial Doppler ultrasound of the middle cerebral artery. Associations between neurovascular indices and cognitive change were assessed with linear regression analyses. RESULTS: On group level, the CEA patients improved more than controls in working memory, whereas no cognitive deterioration was detected. Also on individual level, improvement was most frequently observed in working memory. Worse preoperative cerebrovascular reactivity was related with improvement in cognitive functions of the ipsilateral hemisphere. Low preoperative pulsatility index was associated with improvement in executive functioning and ipsilateral cognitive functions. Poorer preoperative blood flow velocity associated with improvement in complex attention. Microembolic signals were rare. CONCLUSION: The present findings suggest that CEA may have beneficial long-term effects on cognition. These effects may specifically involve patients with impaired preoperative circulatory adaptive mechanisms.

Thirty-day outcomes of carotid endarterectomy versus carotid artery stenting in asymptomatic and symptomatic patients: a propensity score-matched analysis.

BACKGROUND: Technological and surgical approaches to carotid artery stenting (CAS) have evolved. Modern randomised controlled trials comparing CAS and carotid endarterectomy (CEA) are limited, and information about updated post-intervention outcomes are mostly from retrospective, small studies. AIMS: This study aims to compare the 30-day outcomes of stroke, transient ischaemic attack (TIA), acute myocardial infarction (AMI) and death with propensity-matched groups of CEA and CAS in asymptomatic and symptomatic patients over a recent study period of new CAS technologies and approaches. METHODS: A retrospective, observational, multicentre analysis was conducted including consecutive symptomatic and asymptomatic patients treated with either primary CEA or CAS for internal carotid artery stenosis, between 2015 and 2022. Patients were propensity score-matched based on comorbidities and assessed according to symptom status. Primary endpoints include composite ipsilateral stroke, TIA, AMI and death within 30 days. Secondary endpoints include technical success and length of hospital stay. RESULTS: From a cohort of 1,110 patients, propensity matching produced 269 distinct treatment pairs (n=538). Most patients were asymptomatic (n=456, 85%). All 6 strokes were minor (CEA=2; CAS=4) and registered among asymptomatic patients. One AMI (CEA) and 1 patient death (CAS) were reported among symptomatic patients. Composite stroke/AMI/death were not significantly different between both types of symptom status and both revascularisation techniques (p=0.44 and p=1, respectively). Technical success was 100%. The length of hospital stay was significantly shorter in asymptomatic patients treated with CAS compared to those treated with CEA (p=0.05), but no difference was registered among symptomatic patients (p=0.32). CONCLUSIONS: Propensity-matched analysis suggests that CAS has similar postprocedural outcomes for stroke, AMI and death at 30 days compared to CEA.

Outcomes of carotid endarterectomy: Insights from a single-center retrospective cohort study.

OBJECTIVES: To analyze the outcomes of carotid endarterectomy in individuals with carotid artery stenosis in the context of a tertiary care center. METHODS: We carried out a retrospective cohort investigation between 2015-2022. Patient data includes demographics, risk factors, preoperative medications, and operative details. The primary outcomes were 30-day postoperative stroke and mortality rates, while the secondary outcome of the study was to assess the morbidity of the procedure. RESULTS: The mean age of the 54 patients was 66.9±9.88 years, and 57.4% were men. The 30-day stroke rate was 3.7%, and the mortality rate was 1.9%. Most patients did not develop postoperative complications; however, surgical site hematoma was the most common complication encountered (12.9%). Long-term follow-up showed disease regression in 68.5% of patients, with a minority of patients developing ipsilateral restenosis. Admission to an intensive care monitoring unit was the only independent predictor of postoperative complications. CONCLUSION: This study provided insights into the outcomes of carotid endarterectomy in patients with carotid artery stenosis, emphasizing the importance of careful patient selection and postoperative monitoring. Perioperative risks, including stroke and mortality, were within acceptable limits. Further research incorporating structured and non-structured data for predictive analyses, should explore refining patient profiling and optimizing treatment approaches for different carotid artery stenosis clinical and morphological presentations.

Mathematical modeling in assessing the risk of restenosis after carotid endarterectomy.

Carotid endarterectomy is the main way to combat atherosclerosis of the carotid arteries, which disrupts cerebral circulation. The generally accepted marker of atherogenesis risk are hemodynamic indices associated with near-wall shear stress. The purpose of the work is to conduct a comparative analysis of hemodynamic indices in various carotid bifurcation models. The influence of a virtual change in the geometric shape of the model in order to optimize hemodynamic indices is also being studied. On the basis of computed angiography data, carotid bifurcation models are constructed, in which critical zones of hemodynamic indices are built using computational fluid dynamics. A comparative analysis of the critical zones for different classes of models is carried out. Comparison of averaged indices for critical zones between 'normal' and post-operative groups gave more than 5-x worse results for the latter. The same results for the near-bifurcation parts of the zones give a 25% better result for postoperative models. Virtual 'removal' of insignificant plaques leads to a deterioration of the indices of up to 40% in the places of the plaque's former location. The described method makes it possible to build the indices critical zones and compare them for various types of models. A technique for virtual changing the shape of a vessel (virtual surgery) is proposed. The novelty of the approach lies in the use for comparative analysis both real vessel models and hypothetical 'improved' virtual ones, as well in the proposed division of post-operative model's critical zones into subzones of different genesis.

[Advisability of carotid endarterectomy in asymptomatic patients]. / Tselesoobraznost' karotidnoi endarterektomii u asimptomnykh bol'nykh. Analiticheskii obzor.

OBJECTIVE: To determine the optimal treatment strategy for patients with asymptomatic carotid stenosis. MATERIAL AND METHODS: The authors reviewed clinical guidelines for the management of patients with asymptomatic carotid stenosis 60-99%, as well as medical studies and meta-analyses comparing carotid endarterectomy and optimal drug therapy in asymptomatic patients between 1993 and 2023. RESULTS: The choice of treatment strategy for patients with asymptomatic carotid artery stenosis is still a controversial issue. There were several large randomized clinical trials comparing carotid endarterectomy with optimal medical therapy in asymptomatic patients at the end of the 20th century. However, drug therapy has undergone significant changes calling into question the relevance of previous results. This review highlights the evolution of management of patients with asymptomatic carotid stenosis and also presents modern approaches to the treatment of these patients. CONCLUSION: Patients younger 75 years old gain an advantage from carotid endarterectomy with small perioperative risk compared to optimal drug therapy and yearly risk of cerebral embolism. Patients with asymptomatic carotid stenosis 80-99% are candidates for carotid endarterectomy due to higher risk of acute cerebrovascular accident at least until more data are available. The choice of the best tactics for a particular patient should be made individually depending on own experience and patient's adherence to therapy and lifestyle correction. The results of the ACTRIS (2025) and CREST-2 (2026) studies are expected to clarify this issue.

Comparison Between Conventional and Patch Carotid Endarterectomy: A Single-Center Retrospective Study.

OBJECTIVE: To compare perioperative and long-term safety and effectiveness between conventional carotid endarterectomy (cCEA) and patch carotid endarterectomy (pCEA) under current medical conditions. METHODS: Data on baseline characteristics as well as perioperative and long-term postoperative complications from patients who underwent cCEA or pCEA at the Department of Vascular Surgery, Xuanwu Hospital of Capital Medical University, from 2013 to 2022, were retrospectively collected and analyzed. RESULTS: A total of 248 CEA patients were included in our study. The majority of patients (87.3%) were male, and mean age was 63.6 ± 7.6 (range, 40-81) years; 104 patients (41.9%) underwent cCEA, while 144 (58.1%) underwent pCEA. Between the cCEA and pCEA groups, there were no significant differences in clinical baseline characteristics, occurrence of perioperative or long-term (median, 42.5 [range, 7 to 120] months) complications, and survival whether restenosis-free, asymptomatic or overall. CONCLUSIONS: In a single-center experience, conventional and patch CEA approaches appear similarly safe and effective.

Predictors of Occlusion after Carotid Stenting.

BACKGROUND: Carotid artery stent (CAS) occlusion is a rare complication not well studied. We used a national dataset to assess real world CAS experience to determine the rate of stent occlusion. The purpose of this study was to 1) Identify risk factors associated with CAS occlusion on long-term follow-up (LTFU) and 2) Determine the adjusted odds of death/transient ischemic attack (TIA)/stroke (cerebrovascular accident (CVA)) in patients with occlusion. METHODS: The national Vascular Quality Initiative CAS dataset (2016-2021) comprised the sample. The primary endpoint was occlusion on LTFU (9-21 months postoperatively as defined by the Vascular Quality Initiative LTFU dataset) with secondary endpoint examining a composite of death/TIA/CVA. Descriptive analyses used chi-square and Wilcoxon tests for categorical and continuous variables respectively. Adjustment variables were selected a priori based on clinical expertise and univariate analyses. Multivariable logistic regression was used to model the odds of occlusion and the odds of death/TIA/CVA. Generalized estimating equations accounted for center level variation. RESULTS: During the study period, 109 occlusions occurred in 12,143 cases (0.9%). On univariate analyses, symptomatic indication, prior stroke, prior neck radiation, lesion calcification (>50%), stenosis (>80%), distal embolic protection device (compared to flow reversal), balloon size, >1 stent and current smoking at time of LTFU were predictive for occlusion. Age ≥ 65, coronary artery disease (CAD), elective status, preoperative statin, preoperative and discharge P2Y12 inhibitor, use of any protection device intraoperatively and protamine were protective. On multivariable analyses, age ≥ 65, CAD, elective status and P2Y12 inhibitor on discharge were protective for occlusion, while patients with prior radiation and those taking P2Y12 inhibitor on LTFU were at increased odds. The adjusted odds of death/TIA/CVA in patients with occlusion on LTFU were 6.05; 95% confidence interval: 3.61-10.11, P < 0.0001. CONCLUSIONS: This study provides an in-depth analysis of predictors for CAS occlusion on LTFU. On univariate analyses, variables related to disease severity (urgency, degree of stenosis, nature of lesion) and intraoperative details (balloon diameter, >1 stent) were predictive for occlusion. These variables were not statistically significant after risk adjustment. On multivariable analyses, prior neck radiation was strongly predictive of occlusion. Elective status, patient age ≥ 65, CAD, and P2Y12 inhibitor upon discharge (but not on LTFU) were protective for occlusion. Additionally, patients who developed occlusion had high odds for death/TIA/CVA. These findings provide important data to guide clinical decision-making for carotid disease management, particularly identifying high-risk features for CAS occlusion. Closer postoperative follow-up and aggressive risk factor modification in these patients may be merited.

Clinical Significance of Carotid Endarterectomy and Carotid Artery Stenting in Older Patients Over 80.

As the average life expectancy increases, neurosurgeons are likely to encounter patients aged 80 years and above with carotid stenosis; however, whether old age affects clinical post-treatment outcomes of carotid endarterectomy (CEA) or carotid artery stenting (CAS) remains inconclusive. Thus, this study aimed to evaluate the outcomes following CEA or CAS in patients aged 80 years and above. This study included older over 80 years (n = 34) and younger patients (<80 years; n = 222) who underwent CEA or CAS between 2012 and 2022. All of them were followed up for a mean of 55 months. All-cause mortality, the incidence of vascular events, ability to perform daily activities, and nursing home admission rates were assessed. During follow-up periods, 34 patients (13.3%) died due to coronary artery disease, malignancy, and pneumonia, and the incidence was significantly higher in the elderly group than in the younger group (P = 0.03; HR, 3.01; 95% CI, 1.53-5.56). The incidence of vascular events did not differ between the older group (29.5%) and the younger group (26.9%, P = 0.58); however, the incidence was significantly higher in patients with high-intensity plaques than in those without that (P = 0.008; HR, 2.83, 95%CI, 1.27-4.87). The decline in the ability to perform daily activities and increased nursing home admission rates were high in elderly patients (P < 0.01). Although the mortality rate was higher in the elderly group, subsequent vascular events were comparable to that in the younger group. The results suggest that CEA and CAS are safe and useful treatments for carotid stenosis in older patients, especially to prevent ipsilateral ischemic stroke.

Carotid Near-Occlusion: Surgical or Conservative Management? Retrospective Multicenter Study.

BACKGROUND: Carotid near-occlusion (CNO) represents an anatomical-functional condition characterized by severe (more than 90%) internal carotid artery stenosis which can lead to a distal lumen diameter greater or less than 2 mm. CNO can be divided into a less severe subgroup (without lumen full collapse: diameter >2 mm) and a more severe subgroup (with lumen full collapse: diameter <2 mm). The decision for revascularization is still highly debated in Literature. The aim of the present multicenter retrospective study is to analyze the incidence of perioperative (30 days) and follow-up complications in 2 groups of patients with or without distal internal carotid lumen full collapse. METHODS: Between January 2011 and March 2023, in 5 Vascular Surgery Units, 67 patients (49 male, 73% and 18 females, 27%) with CNO underwent carotid endarterectomy: 28 (41.7%) with lumen diameter <2 mm and 39 (58.3%) with diameter >2 mm. 19 patients were symptomatic and 48 asymptomatic. The outcomes considered for comparative analysis were: perioperative neurological and cardiac complications, carotid restenosis or occlusion at follow-up. Both groups were homogeneous in terms of risk factors, morphological features and pharmacological treatments. RESULTS: In the group with lumen <2 mm, 3 perioperative major events (10.7%) occurred (1 ischemic stroke, 1 hemorrhagic stroke, 1 myocardial infarction) and 2 (7.1%) at follow-up (average 11 ± 14.5 months; 1 asymptomatic carotid occlusion, 1 hemodynamic restenosis treated with stenting). No event was recorded in the group with lumen >2 mm. CONCLUSIONS: According to our results CNO patients show different complication risk according to the presence or not of distal lumen collapse. The later seems to play a significant role in perioperative and follow-up complication rate. These results therefore support a surgical treatment only in patients with CNO without lumen full collapse.

The 5-Factor Modified Frailty Index is a Concise and Effective Predictor of 30-Day Adverse Outcomes in Carotid Endarterectomy.

INTRODUCTION: Frailty is a clinically identifiable condition characterized by heightened vulnerability. The 5-item Modified Frailty Index provides a concise calculation of frailty that has proven effective in predicting adverse perioperative outcomes across a variety of surgical disciplines. However, there is a paucity of research examining the validity of 11-item Modified Frailty Index (mFI-5) in carotid endarterectomy (CEA). This study aimed to investigate the association between mFI-5 and 30-day outcomes of CEA. METHODS: Patients underwent CEA were identified from American College of Surgeons National Surgical Quality Improvement Program targeted database from 2012 to 2021. Patients with age<18 were excluded. Patients were stratified into four cohorts based on their mFI-5 scores: 0, 1, 2, or 3+. Multivariable logistic regression was used to compare 30-day perioperative outcomes adjusting for preoperative variables with P value<0.1. RESULTS: Compared to controls (mFI-5 = 0), patients mFI-5 = 1 had higher risk of stroke (adjusted odds ratio [aOR] = 1.333, P = 0.02), unplanned operation (aOR = 1.38, P < 0.01), and length of stay (LOS) > 7 days (aOR = 0.814, P < 0.01). Patients with mFI-5 = 2 had higher stroke (aOR = 1.719, P < 0.01), major adverse cardiovascular events (MACE) (aOR = 1.315, P = 0.01), sepsis (aOR = 2.243, P = 0.01), discharge not to home (aOR = 1.200, P < 0.01), 30-day readmission (aOR = 1.405, P < 0.01). Compared with controls, patients with mFI-5≥3 had higher mortality (aOR = 1.997 P = 0.02), MACE (aOR = 1.445, P = 0.03), cardiac complications (aOR = 1.901, P < 0.01), pulmonary events (aOR = 2.196, P < 0.01), sepsis (aOR = 3.65, P < 0.01), restenosis (aOR = 2.606, P = 0.02), unplanned operation (aOR = 1.69, P < 0.01), LOS>7 days (aOR = 1.425, P < 0.01), discharge not to home (aOR = 2.127, P < 0.01), and 30-day readmission (aOR = 2.427, P < 0.01). CONCLUSIONS: The mFI-5 is associated with 30-day mortality and complications including stroke, MACE, cardiac complications, pulmonary complications, sepsis, and restenosis. Additionally, elevated mFI-5 scores correlate with an increased likelihood of unplanned operations, extended LOS, discharge to facilities other than home, and 30-day readmissions, all of which could negatively impact long-term prognosis. Therefore, mFI-5 can serve as a concise yet effective metric of frailty in patients undergoing CEA.

[Evolution of surgical approaches to carotid bifurcation]. / Evolyutsiya khirurgicheskikh dostupov k bifurkatsii sonnoi arterii.

Carotid endarterectomy is preferable for prevention of acute cerebrovascular accident associated with atherosclerotic lesions of internal carotid artery. Modern interest in minimizing local complications and small excisions is also actual in carotid surgery. The authors review the modern literature data on evolution of carotid arteries exposure. Cutaneous mini-incision, transverse skin incision and retrojugular approach are discussed. The authors consider the advantages and possible complications of each technique.

Association of Impedance Aggregometry-Measured Platelet Aggregation With Thromboembolic Events in Patients Who Undergo Carotid Endarterectomy: A Pilot Study.

OBJECTIVES: The aim of the current study was to assess the relationship among thrombin receptor activator peptide 6 (TRAP test), adenosine-5'-diphosphate (ADP test), arachidonic acid (ASPI test), and stroke/transient ischemic attack (TIA), using the multiple electrode aggregometry (Multiplate) in patients undergoing carotid thromboendarterectomy (CEA). DESIGN: A retrospective study. SETTING: Vascular surgery operating rooms of a university hospital. PARTICIPANTS: One hundred thirty-one out of 474 patients undergoing CEA between November 2020 and October 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A preoperative blood sample of all enrolled patients was analyzed using the Multiplate analyzer. Receiver operating characteristics curves, were generated to test the ability of TRAP, ADP, and ASPI in discriminating perioperative thromboembolic stroke/TIA. A logistic LASSO regression model was used to identify factors independently associated with stroke/TIA. Eight patients experienced a perioperative stroke/TIA. Although all the platelet functional assays showed excellent predictive performance, an ADP value exceeding 72 U showed the highest specificity (87%) and sensitivity (68%) in discriminating patients who had a perioperative thromboembolic stroke/TIA, with a negative predictive value of 99% and a positive predictive value of 15%. After LASSO regression, an ADP >72 U and the need for a shunt during CEA were the only 2 variables independently associated with perioperative stroke/TIA. CONCLUSION: Because the ADP test was independently associated with perioperative stroke/TIA, the assessment of platelet reactivity using Multiplate may offer potential utility in monitoring patients undergoing CEA.

Association between preoperative white matter hyperintensities and postoperative new ischemic lesions on magnetic resonance imaging in patients with cognitive decline after carotid endarterectomy.

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78-28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42-571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA.

Similar long-term outcomes for venous, bovine pericardial, and polyester patches for primary carotid endarterectomy.

BACKGROUND: Currently, the type of patch used for carotid endarterectomy closure depends on the preference of the operating surgeon. Various materials are available, including autologous venous patches, bovine pericardial patches (BPP), and synthetic patches. The purpose of this study was to compare the long-term outcomes. METHODS: All patients who underwent primary carotid endarterectomy with patch angioplasty using a venous, bovine, or polyester patch between 2010 and 2020 at two high-volume medical centers were included in this retrospective analysis on largely prospectively collected data. Study endpoints included long-term ipsilateral transient ischemic attack or cerebrovascular accident, restenosis, reintervention, and all-cause mortality. Cox proportional hazard models were fitted to assess the effect of patch type to each outcome. RESULTS: In total, 1481 CEAs were performed with a follow-up of 32 (13-65) months. Venous patch was used in 309 patients (20.9%), BPP in 1000 patients (67.5%), and polyester patch in 172 patients (11.6%). A preoperative symptomatic carotid artery stenosis of >50% was observed in 91.9% (n = 284) of the patients who received a venous patch, 92.1% (n = 921) of the patients who received BPP, and 90.7% (n = 156) of the patients who received a polyester patch (p = 0.799). Only in selected patients with an asymptomatic stenosis of >70% surgery was considered. Multivariable analyses showed no significant differences between the three patch types regarding long-term outcomes after adjusting for confounders. CONCLUSIONS: In patients undergoing primary carotid endarterectomy, the use of venous, bovine pericardial, or polyester patches seems equally safe and durable in terms of comparability in long-term outcomes.

Nasal Intubation is not Associated with "Smoother" Emergence from General Anesthesia for Carotid Endarterectomy: A Case-Cohort Study.

BACKGROUND: Postoperative hematoma after carotid endarterectomy (CEA) is a devastating complication and may be more likely in patients with uncontrolled hypertension and coughing on emergence from anesthesia. We sought to determine if intubation with a nasal endotracheal tube (ETT)-instead of an oral ETT-is associated with "smoother" (i.e., less hemodynamic instability) emergence from general anesthesia for CEA. METHODS: Patients receiving CEA between December 2015 and September 2021 at a single tertiary academic medical center were included. We examined the electronic anesthesia records for 323 patients who underwent CEA during the 6-year study period and recorded consecutive systolic blood pressure (SBP) values during the 10 minutes before extubation as a surrogate for "smoothness" of the emergence. RESULTS: Intubation with a nasal ETT, when compared with intubation with an oral ETT, was not associated with any difference in maximum, minimum, average, median, or standard deviation of serial SBP values in the 10 minutes before extubation. The average SBP on emergence for patients with an oral ETT was 141 mm Hg and with a nasal ETT was 144 mm Hg (P = 0.562). The maximum SBP for patients with oral and nasal ETTs were 170 mm Hg and 174 mm Hg, respectively (P = 0.491). There were also no differences in the qualitative "smoothness" of emergence or in the percentage of patients who required an intravenous dose of 1 or more antihypertensive medications. The incidence of postoperative complications was similar between the 2 groups. CONCLUSIONS: When SBP is used as a surrogate for smoothness of emergence from general anesthesia for CEA, intubation with a nasal ETT was not associated with better hemodynamic stability compared to intubation with an oral ETT.

The mid-term results of the Carotid Asymptomatic Stenosis (CARAS) observational study.

INTRODUCTION: Carotid endarterectomy (CEA) in patients with asymptomatic carotid stenosis (ACAS) remains a subject of debate. Current recommendations are based on randomized trials conducted over 20 years ago and improvements in medical therapies may have reduced the risk of cerebral ischemic events (CIE). This study presents a mid-term analysis of results from an ongoing prospective observational study of ACAS patients to assess their CIE risk in a real-world setting. METHODS: This is a prospective observational cohort study of patients with ACAS >60 % (NASCET criteria) identified in a single duplex ultrasonography (DUS) vascular laboratory (trial registered: NCT04825080). Patients were not considered for CEA due to their short life expectancy (<3 year) or absence of signs of plaque vulnerability (ulceration, ipoechogenic core). Patient enrollment started in January 2019 and ended in March 2020 with a targeted sample size of 300 patients.A 5-year follow-up was scheduled. Clinical characteristics, risk factors, and medical therapies were documented, and, when necessary, the best medical therapy (BMT), involving antiplatelet agents, blood pressure control, and statins, was recommended during clinical visits. The primary endpoint was to asses CIEs (including strokes, transient ischemic attacks, amaurosis-fugax) ipsilateral to ACAS along with plaque progression rate and patients survival. Follow-up involved annual clinical visit and carotid DUS examination, complemented by telephone interviews at six-month intervals. RESULTS: The study included 307 patients, with an average age of 80 ± 7 years, of whom 55 % were male. Contralateral stenosis exceeding 60 % was present in 61 (20 %) patients. Seventy-seven percent of patients were on BMT. At a mean follow-up of 41±9 months, 7 ispilateral strokes and 9 TIAs occurred, resulting in 14 CIEs (2 patients experienced both TIA and stroke). According to Kaplan-Meier analysis, the 4-year CIE rate was 6±2 %, with an annual CIE rate of 1.5 %. Fifty-eight (19 %) patients had a stenosis progression which was associated with a higher 4-year estimated CIE rate compared to patients with stable plaque (10.3 % vs 3.2 %, P=.01). Similarly, a contralateral carotid stenosis >60 % was associated with a higher 4-year estimated CIE rate: 11.7 % vs 2.9 %, P=.002. These factors were independently associated with high risk for CIE at the multivariate COX analysis: Hazard Ratio (HR): 3.2; 95 % Confidence Interval: 1.1-9.2 and HR: 3.6; 95 % CI: 1.2-10.5. CONCLUSION: The mid-term results of this prospective study suggest that the incidence of CIE in ACAS patients should not be underestimated, with plaque progression and contralateral stenosis serving as primary predictors of CIEs.