The Comparative Study Of PTAS And Medical Management On Symptomatic Intracranial Atherosclerotic Stenosis

Background: Stroke is a common and frequently-occurring disease in China.It has the features of high morbidity,high disability,high mortality,high recurrence rate,and high economic burden.Intracranial atherosclerotic stenosis(ICAS)is the most important factor leading to ischemic stroke,more commonly in Asians.Since the patients of Asian are at higher risk of ICAS,it highlights the need for the diagnosis and treatment of ICAS in the prevention and treatment of ischemic stroke in China.According to whether there is ischemic stroke or transient ischemic attacks(TIA)occurring in the vascular territory of the stenosed or occluded artery,ICAS is classified into two types: one is symptomatic intracranial atherosclerotic stenosis(sICAS)and the other is asymptomatic intracranial atherosclerotic stenosis(a ICAS).s ICAS has an high recurrence rate and has a positive correlation with the degree of arterial stenosis.The treatment of sICAS remains controversial nowadays.The WASID(Warfarin versus Aspirin Symptomatic Intracranial Disease Study for Stroke)study showed that the mean follow-up 1.8 year recurrence rate of sICAS patients with 70% to 99% stenosis remained as high as 19% despite of undertaking medical therapy[1].Alternative treatments,such as percutaneous transluminal angioplasty and stenting(PTAS),may be one of the effective methods for these patients.Moreover,some non-randomized studies had encouraging data regarding potential safety and efficacy for PTAS in s ICAS [2].However,enrollment in SAMMPRIS(Stenting versus aggressive medical therapy for intracranial arterial stenosis)study was stopped in advance in 2011 because the 30-day rate of the primary endpoint event was significantly higher in the stenting arm than that in the medical arm(14.7% versus 5.8%)[3].As the SAMMPRIS study is the first multicenter prospective randomized controlled study,aggressive medical management(AMM)is recommended in preference to PTAS for sICAS patients.From then on,it casts a shadow on endovascular treatment.After SAMMPRIS trial has released their results,many scholars have significant criticism on inclusion criteria,center selection,surgeons’ technical experience,and management of the primary risk factors and a lifestyle modification program in AMM not being able to achieve in the real-world.There is no guiding significance for treatment of sICAS patients in a real-world in our country.Furtherfore,stroke becomes a major problem in China and many domestic medical centers still adopt PTAS as the main therapy for sICAS patients at present.Considering that we have difficulties conducting randomize controlled trial(RCT),it is of great importance to investigate the difference of effect between endovascular treatment and AMM.Our study aims to investigate the safe and optimal treatment strategy of patients with s ICAS in the Neurology Department of Southwest Hospital of Third Military Medical University.The result of our trial will provide the therapy regimen for s ICAS patients with reference.The study consists of two parts,one is a retrospective study,the other is a prospective controlled study.Objective:1.To observe the safety and efficacy of endovascular treatment in our medical center,compared with medical management;2.To observe the effects of PTAS and medical management on the arterial stenosis;3.To observe the effects of PTAS and medical management on the nerve function recovery.Methods:1.A retrospective study of the efficacy of PTAS and medical management for sICAS patients in preventing recurrent ischemic stroke/TIA(1)We performed a retrospective analysis of case records and imaging data of s ICAS patients with 50% ~99% stenosis of a major intracranial artery who underwent digital subtraction angiography(DSA)at our institution between January 2009 and December 2014,observing the differences between medical management and PTAS;(2)Data were collected from s ICAS patients in telephone follow-up period,including monitoring the incidences of complications during the 30-day perioperative period,any recurrent ischemic stroke/TIA in the territory of the qualifying artery within 1 year after enrollment,other adverse events(such as hemorrhage,myocardial infarction,and so on),the m RS score and other changes;(3)Statistical analysis of recurrent stroke/TIA,adverse events and other events.2.A prospective study of the efficacy of PTAS and medical management for sICAS patients in preventing recurrent ischemic stroke/TIA(1)All s ICAS patients have 70%~99% stenosis of a major intracranial artery which are confirmed by DSA(using WASID trial method to calculate the the qualifying artery stenosis).We communicate effectively with the enrolled patients and their families.After they have a good knowledge of the trial designation,they make their choose of PTAS by themselves.If patients change the therapy regimen after giving medical treatment,they will be excluded;(2)The therapy regimen is divided into two arms,the medical management arm: AMM alone,including intensive antithrombotic treatment combined clopidogrel 75 mg per day and aspirin 100 mg per day for 3 months followed by aspirin 100 mg per day or clopidogrel 75 mg per day alone,intensive statin therapy,intensive risk factor management throughout the trial,and a lifestyle modification program;The PTAS arm : patients treated with Individualized PTAS also receive the same AMM;(3)We evaluate any endpoint event and adverse events of subjects at 30 days,3 months,6 months,and 1 year after enrollment by telephone,at the hospital,and at the outpatient clinic.The primary endpoint is any vascular event including death during the first year;The secondary endpoint:1)any stroke or death rate within 30 days;2)The changes of arterial stenosis and the incidences of in-stent stenosis(ISR)and assessment of NIHSS score and m RS score during the follow-up time.Results:1.A retrospective study of the efficacy of PTAS and medical management for sICAS patients in preventing recurrent ischemic stroke/TIA(1)456 patients were retrospectively screened.Finally 245 patients were registered and analyzed(medical management arm and PTAS arm were 181,64 patients respectively).The primary outcome,1-year rate of any vascular events including death of 20.4% versus 9.4%(p<0.05),respectively,showing there were significant difference between the two arms: 27(14.9%)of181 patients in the medical management arm and 2(3.1%)of 64 patients in the PTAS arm had ipsilateral recurrent stroke(p<0.05),showing there were significant difference between the two arms;1-year rate of non-ipsilateral recurrent stroke of 0.5% versus 0%(p>0.05),respectively,showing there were no significant difference between the two arms;2(1.1%)of181 patients in the medical management arm were dead,while there were no death in the endovascular treatment(p>0.05),respectively,showing there were no significant difference between the two arms;(2)A 30-day rate of any stroke or death of 3.9% versus 6.3%(p>0.05)for medical management arm and PTAS arm,respectively,showing there were no significant difference between the two arms.Other adverse events: the incidences of femoral pseudoaneurysm(FPA)of 1.1% versus 0%(p>0.05),respectively,showing there were no significant difference between the two arms;the rate of overall haemorrhage of 6.1% versus 7.8%(p>0.05),respectively,showing there were no significant difference between the two arms;(3)Patients with no obvious or mild neurological disability were defined as mRS score less than 2.The proportion of mRS score that was less than 2 was 63.0%,92.2% in medical management arm and PTAS arm respectively at 1 year(p<0.05),showing there were significant difference between the two arms.2.A prospective study of the efficacy of PTAS and medical management for sICAS patients in preventing recurrent ischemic stroke/TIA(1)Patient Characteristics: 112 consecutive patients were enrolled.76 patients in medical management arm and 36 in the other.By statistical analysis,we found that there are no significant difference in baseline characteristics between the 2 arms;(2)Overall technical success rate is 100%(36/36).Patients underwent angioplasty alone,self-expanding stents,and balloon mounted stents were 2,18,and 16 respectively.1-year rate of any vascular events including death of 19.7% versus 5.6%(p<0.05),respectively,showing there are significant difference between the two arms: 1-year rate of ipsilateral recurrent stroke of 18.4% versus 2.8%(p<0.05),respectively,showing there are significant difference between the two arms;1-year rate of non-ipsilateral recurrent stroke of 3.9%versus 0%(p>0.05),respectively,showing there are no significant difference between the two arms;1-year rate of recurrent TIA of 1.3%versus 0%(p > 0.05),respectively,showing there are no significant difference between the two arms.Patients in both of arms have no acute coronary syndrome and death;(3)The occurrence of secondary endpoints in the medical management arm versus PTAS arm was 0% versus 2.8% at day 30(p>0.05),respectively,showing there are no significant difference between the two arms;Patients in both of arms have no death within 30 days;(4)The stenosis rate were 87.3±11.2(%)versus 13.9±17.5(%)in medical management arm and PTAS arm at 1 year(p<0.05)respectively,revealing there are significant difference between the two arms.In medical management arm,the stenosis rate is 86.1±12.3(%)versus 87.3±11.2(%)in before and after treatment arm(p <0.05),showing there are significant difference between the two arms.In PTAS arm,the preoperative stenosis rate and the postoperative residual stenosis rate are 83.9±10.3(%)and 10.1±7.6(%)(p<0.05)respectively,showing there are significant difference between the two arms.the stenosis rate is 83.9±10.3(%)versus 13.9±17.5(%)in before and after PTAS arm(p<0.05)respectively,showing there are significant difference between the two arms.The in-stent rate(ISR)is 8.8%;(5)The effects of endovascular treatment on the neurological function: cases of patients whose NIHSS score less than 3 are 69 versus 34 in medical management armand PTAS arm(p>0.05)respectively,showing there are no significant difference between the two arms;cases of patients whose mRS score less than 2 are 62 versus 35(p<0.05)respectively,showing there are significant difference between the two arms;In medical management arm,cases of patients whose NIHSS score less than 3 are 48 versus 69 in before and after treatment arm(p<0.05),showing there are significant difference between the two arms;cases of patients whose m RS score less than 2 are 76 versus 62 in before and after treatment arm(p<0.05),showing there are significant difference between the two arms;In PTAS arm,cases of patients whose NIHSS score less than 3 are 26 versus 34 in before and after treatment arm(p<0.05),showing there are significant difference between the two arms;cases of patients whose m RS score less than 2 are 36 versus 35 in before and after treatment arm(p>0.05),showing there are no significant difference between the two arms.Conclusions1.Endovascular treatment can prevent recurrent ischemic stroke/TIA for s ICAS patients within one year and is superior to aggressive medical management alone;2.Prudent selection of suitable patients and using individualized endovascular treatment is feasible and safe in s ICAS patients;3.The stenosis rate of stenosed lesion do not be dramatically improved with aggressive medical management alone,whereas aggressive medical management and endovascular treatment not only can obviously alleviate the luminal narrowing,but also can evidently improve neurological function between before and after treatment;4.Endovascular treatment can be regarded as a potential safe and effective therapy in high-risk sICAS patients.