溶栓相关试验及进展.

急性缺血性脑卒中血管再通临床证据与进展首都医科大学宣武医院神经外科王亚冰缺血性脑卒中溶栓治疗循证•静脉溶栓（NINDS，ECASSIII）•动脉溶栓（PROACT）•动静脉溶栓（IMS）•机械取栓（MERCI，SEIS）•指南•其他证据静脉溶栓治疗•美国FDA批准临床应用----1995年NINDS研究证明3h内静脉注射重组组织纤溶酶原激活剂（rtPA）溶栓治疗的有效性•AHA:----2008年欧洲急性卒中协作ECASSIII研究表明静脉rtPA溶栓治疗的时间窗可延长至4.5h静脉rtPA溶栓的不足•受益患者少-仅1-3%的患者能够在发病3h内接受治疗•血管再通率较低-仅约6%的颈内动脉、30%大脑中动脉和30%椎基底动脉可获得血管再通39岁女性，意识障碍2小时A：T2相正常B、C：DWI显示右侧MCA分布区细胞毒性水肿，以右侧放射冠明显动脉内溶栓治疗3天后复查D：病变范围无增大，仅皮层及放射冠有小梗塞灶。Dismatch未行溶栓治疗的病例缺血性脑卒中的早期治疗血管再通临床有效发现新策略!↑缺血区的血流灌注缺血性脑卒中•血管再通：早期治疗关键----NINDS：1995年，静脉溶栓，3h----ECASS-Ⅲ：2008年，静脉溶栓，4.5h----大血管闭塞（ICAT--6%，TCD）•发展：----大血管闭塞（ICA，MCA，VA，BA）----Real-timewindow至病理生理时间窗----多模式的血管内治疗（单纯/合并）有效快速容易复杂血管内机械再通治疗PROACTIIMERCIMultiMERCIPenumbraNINDSIVrtPAN121141164125182Age6467686468NIHSS1720191817Recanalization66%48%68%82%N/AsICH10%7.8%9.8%11.2%6.6%90daysmRS≤240%27.7%36%25%39%90daysmortality25%43.5%34%32.8%21%TheImpactofRecanalizationonIschemicStrokeOutcomeAMeta-Analysisspontaneous(24.1%),intravenousfibrinolytic(46.2%),intra-arterialfibrinolytic(63.2%),combinedintravenous–intra-arterial(67.5%),andmechanical(83.6%)recanalizedversusnonrecanalized:oddsratioof4.43(95%CI,3.32to5.91)mortalitywasreducedinrecanalizedpatients(oddsratio,0.24;95%CI,0.16to0.35)SICH:didnotdifferbetweenthe2groupsStroke.2007;38:967-973;Anteriorcirculation:randomizedthrombolysistrialsinhemisphericstrokeNINDS:NationalInstituteofNeurologicalDisordersandStroke;ECASS:EuropeanCooperativeAcuteStrokeStudyPROACT:ProlyseinAcuteCerebralThromboembolismPosteriorcirculation:MajortreatmentstudiesinacutevertebrobasilarocclusionIVT:intravenousthrombolysis;LIT:localintraarterialthrombolysis;GuidelinesfortheEarlyManagementofPatientsWithAcuteIschemicStroke•IntravenousrtPA•推荐对起病3小时内符合标准的缺血性卒中患者静脉输注rtPA（0.9mg/kg，最大剂量90mg），I级推荐，A级证据。•推荐有适应征、起病后3-4.5小时的卒中患者使用静脉用rtPA（0.9mg/kg，最大剂量90mg），I级推荐，B级证据。AHA/ASAGuidelineGuidelinesfortheEarlyManagementofPatientsWithAcuteIschemicStroke•EndovascularInterventions•时间窗内：静脉优先于动脉（I级推荐，A级证据）•对于大脑中动脉大面积缺血性卒中患者，病程小于6小时的，动脉内溶栓治疗审慎选择的患者（他们不适合使用rtPA治疗）可以获益。（I级推荐，B级证据）。•机械取栓方面，支架取栓器（如SolitaireFR和Trevo）总体上优于弹簧圈取栓器（如Merci）。Penumbra系统相较支架取栓器的相对效果尚不明确。I级推荐，A级证据。•联合溶栓：对于大动脉梗死静脉溶栓没有出现应答的患者进行补救性动脉内溶栓或机械取栓术是合理的。需要更多的随机试验结果（IIb级推荐，B级证据）。•急诊颅内血管成形术和/或支架置入的效果尚不肯定。AHA/ASAGuidelineSWIFTTrial：Solitaire〉MerciMerciRetrievalDeviceX6、X5；L5；Kmini、VPenumbraSystemThrombusaspirationandproximalthrombectomyFDA2007PenumbraSystem支架回收机械取栓支架回收机械取栓Castanoetal.Stroke2010;41:1836-40Endovasculartreatmentofacuteischemicstroketheendorthebeginning??•IMSIIII:interventionalManagementofStroke•MRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomy•SYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014BridgingTherapyBridgingTherapyinAcuteIschemicStroke:ASystematicReviewandMeta-Analysis•SystematicreviewofallstudiesusingbridgingtherapypublishedbetweenJanuary1966andMarch2011•Theliteraturesearchidentified15studies.•Inthismeta-analysis,pooledestimatesassociatedwithbridgingtherapywere69.6%forrecanalizationrates,48.9%forfavorableoutcome,17.9%formortality,and8.6%forsICH.Stroke.2012;43:1302-1308PooledRatesofRecanalizationandClinicalOutcomesConclusions—Bridgingtherapyisassociatedwithacceptablesafetyandefficacyinstrokepatients.Timetointravenoustreatmentiscriticaltoimproverecanalizationratesandfavorableoutcomes.IMSIIItrial•EndovascularTherapyafterIntravenoust-PAversust-PAAloneforStroke•within3hours•Stoppedearlybecauseoffutilityafter656participantshadundergonerandomization(434patientstoendovasculartherapyand222tointravenoust-PAalone)NEnglJMed.2013March7;368(10):893–903.IMSIIItrialIMSIIItrial•CONCLUSIONS—Similarsafetyoutcomesandnosignificantdifferenceinfunctionalindependencewithendovasculartherapyafterintravenoust-PA,ascomparedwithintravenoust-PAaloneNEnglJMed.2013March7;368(10):893–903.Endovasculartreatmentofacuteischemicstroketheendorthebeginning??•IMSIIII:interventionalManagementofStroke•MRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomy•SYNTHESISExpansion:ARandomizedControlledTrialonIntra-ArterialVersusIntravenousThrombolysisinAcuteIschemicStrokeNeurosurgFocus36(1):E5,2014MRRESCUEATrialofImagingSelectionandEndovascularTreatmentforIschemicStrokeAfavorablepenumbralpatternonneuroimagingdidnotidentifypatientswhowoulddifferentiallybenefitfromendovasculartherapyforacuteischemicstroke,norwasembolectomyshowntobesuperiortostandardcare.SWIFTTrial•美国多中心、随机对照研究•血管内机械再通治疗颅内大血管闭塞•SolitaireRetrievervsMerciRetriever•主要疗效终点：成功血管再通、无症状性出血•次要疗效终点：良好临床结局、死亡率和严重并发症Saveretal.ISC2012FebSWIFTTrial:RandomizedEndpointSolitaireFR(n=58)Merci(n=55)Successfulrecanalizationstudydevice83.3%48.1%Endofproceduresuccessfulrecanalization88.9%67.3%SuccessfulrecanalizationwithoutsICH60.7%24.1%mRS≤2at90Days58.2%33.3%Mortalityat90Days17.2%33.3%AllP0.001Endovasculartreatmentofacuteischemicstroketheendorthebeginning??•IMSIIII:interventionalManagementofStroke•MRRESCUE:MechanicalRetrievalandRecanalizationofStrokeClotsUsingEmbolectomy•SYNTHESISExpansion:ARandomizedControlledTr