Ischemic Brain Injury After Carotid Stenting

Part OneBackground Research conducted in Western countries has suggested that high-dose statin therapy can lead to the regression of carotid atherosclerotic plaques and can reduce periprocedural ischemic complication rates in individuals undergoing carotid artery stenting(CAS).However,whether this same therapeutic approach is of value in patients of Chinese ethnicity is not as well-established.Methods This is a single-center,prospective,parallel-controlled,intervention-based efficacy study that will enroll a total of 130 Asian patients with cervical carotid stenosis who are scheduled to undergo CAS.These patients will be randomly divided into a routine treatment group and a high-dose atorvastatin group.Individuals in the routine treatment group will be administered standard of care 20 mg/day atorvastatin treatment.Individuals in the high-dose atorvastatin group will be administered 80 mg/day atorvastatin for 3 days prior to and following CAS.The primary outcome of this study will be the cumulative incidence of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging(DW-MRI)within 5 days following CAS,and of transient ischemic attacks(TIAs)or ischemic stroke within 30 days after CAS.Results and conclusion This study is the first to assess whether high-dose atorvastatin treatment can reduce the incidence of perioperative cerebral ischemic injury in patients of Asian ethnicity undergoing CAS.These results will offer evidence regarding which statin treatment regimens are more appropriate when treating Chinese patients undergoing CAS to minimize their risk of any perioperative cerebral ischemic injury.Part TwoBackground Preoperative administration of high-dose atorvastatin(80 mg/day)to patients who underwent carotid stenting(CAS)reduces the incidence of ischemic lesions in the perioperative period of carotid stenting(CAS).Still,more high-level evidence is needed,and the dose and duration of perioperative statin therapy are not yet known.This study used a perioperative,high-dose atorvastatin treatment strategy to explore whether high-dose atorvastatin treatment could reduce the risk of perioperative ischemic brain injury in patients with CAS assess whether there was a difference in the safety of the two doses of statin treatment.Methods A Single-center,double-blind,placebo-controlled,randomized clinical trial conducted in the Department of Neurosurgery at Beijing Hospital among 130 patients with carotid artery stenting(CAS),who were randomized into a high-dose group(80 mg/day)and a standard-dose group(20 mg/day).Enrollment occurred between August 2017 to April 2020.The high-dose group was given 80mg of atorvastatin per day for 3 days before and after CAS treatment.The standard dose group was given 20mg of atorvastatin.The primary endpoint outcomes were the cumulative incidence of new ischemic lesions on diffusion-weighted magnetic resonance imaging(DW-MRI)within 5 days after CAS and the cumulative incidence of transient ischemic attacks(TIAs)or ischemic stroke within 30 days after CAS.Secondary endpoint outcomes were the incidence of new cerebral ischemic lesions on DW-MRI within 1-5 days postoperatively;the number of new cerebral ischemic lesions on DW-MRI and the incidence of lesions>5 mm in size within 1-5 days post CAS;the incidence of TIAs or ischemic stroke within 30 days post CAS;the incidence of all-cause death,any stroke or myocardial infarction at 30 days postoperatively;the incidence of all-cause death,any stroke or myocardial infarction within 30 days of CAS;bleeding events at 30 days of CAS and puncture site complications.Result A total of 130 patients were enrolled,65 in the high-dose group and 63 completed the trial;65 in the standard-dose group and 60 completed the trial.There was no significant difference between the two groups in terms of demographic data and serological examination at baseline(P>0.05).There was no side effect related to the two groups.In both groups,postoperative alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum creatinine(Scr)and blood urea nitrogen(BUN)levels were lower in CAS compared to preoperative levels(P<0.05),with no adverse effects on liver or renal function.The incidence of the primary endpoint event was 69.8%(44 cases)in the high-dose group and 78.3%(46 cases)in the standard-dose group,with no significant difference between the two groups(P>0.05).For the secondary endpoint outcome,the incidence of new ischemic lesions with a maximum diameter greater than 5 mm was 44.4%(28 cases)vs 40%(24 cases),respectively,with no significant difference between the two groups(P>0.05).In patients with symptomatic carotid stenosis,the incidence was 55.6%(15/27)in the high-dose group and 82.6%(19/23)in the standard-dose group,with a significant difference in the incidence of asymptomatic new ischaemic foci between the two groups,p=0.04<0.05,HR=0.263,95%CI 0.70-0.984.Conclusions The effect of high-dose atorvastatin in the perioperative period was significant,and the safety profile was reliable.Perioperative high-dose atorvastatin treatment did not reduce the incidence of new ischemic lesions in the perioperative period and major adverse cardiovascular events in Asian patients treated at 30 days with CAS surgery.These results do not support the routine use of high-dose atorvastatin therapy in unselected CAS patients in the perioperative period.Part ThreeObjectives The risk of silent new ischemic cerebral lesions(sNICL)detected by diffusion-weighted imaging(DW-MRI)associated with after carotid artery stenting(CAS)is unclear.We aimed to determine predictors of sNICL detected by DW-MRI following CAS in a secondary analysis of the Effects of High Dose of Atorvastatin for Preventing Periprocedural Ischemic Brain Damage in Patients Undergoing Carotid Artery Stenting(PICAS).Methods PICAS was a single-centre,prospective,randomised controlled study that included a total of 130 patients with carotid stenosis who were scheduled to undergo CAS in Beijing hospitals.A post-hoc exploratory analysis was conducted for this study PICAS,collecting patients in the PICAS study with complete DW-MRI data within 5 days before and after the CAS procedure.According to the occurrence of perioperative sNICL the patients were divided into sNICL group(n=87),non-sNICL group(n=76).The male gender,age(per add 1 year)and smoking history of the patients in the two groups were counted respectively,and the data were tested by independent sample t test,?2 test and Fisher exact probability test.The factors of P<0.2 were considered as the potential factors affecting the new ischemic foci.Multivariate logistic regression analysis was used to analyze the different factors between the two groups to screen the independent risk factors of sNICL in patients with CAS.And the corresponding nomograph prediction model for the risk of sNICL in CAS patients was established.The risk scores for patients developing sNICL were therefore obtained based on the above-mentioned nomograph,and the corresponding receiver operating characteristic(ROC)curve was drawn to calculate the area under the curve.The internal validation of the above-mentioned sNICL prediction model was performed using the Bootstrap method.A calibration curve was drawn to assess the predictive conformity of the above-mentioned sNICL prediction model for the occurrence of sNICL in CAS patients.Results In the PICAS study,all patients successfully completed the operation.All patients used open-loop stents and distal protection devices,and 7 patients were excluded because of DW-MRI deficiency or failure to meet the trial time requirements.A total of 123 patients were enrolled in the study.The incidence of sNICL after CAS was 70.3%(the incidence of 87).Univariate analysis showed that age,ulcer plaque,dyslipidemia,stenosis,residual stenosis and male patients may be the influencing factors of sNICL.Multivariate logistic regression analysis showed that age(OR=1.064,95%CI 1.010-1.120)and ulcer plaque(OR=2.574,95%CI 1.146-5.780)were independent risk factors for sNICL in CAS patients.The area under the ROC curve of the above-mentioned sNICL prediction model was 0.71.When applying the above-mentioned sNICL prediction model for sNICL incidence prediction,there might be some risk of overestimating sNICL incidence when the prediction probability was 65%-82.5%,and some risk of underestimating sNICL incidence when the prediction probability was<65%or>82.5%.Conclusion Age(per add 1 year)and ulcer plaque are independent risk factors for sNICL in patients with CAS.The risk prediction models based on these two indicators has good predictive ability for sNICL in CAS patients.