缺血性卒中抗栓循证治疗.ppt
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缺血性卒中抗栓循证治疗.ppt
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缺血性卒中抗栓循证治疗缺血性卒中抗栓循证治疗证据等级I类证据随机对照试验,假阳性和假阴性错误低II类证据随机对照试验,假阳性和假阴性错误高III类证据非随机对列研究IV类证据回顾性非随机对列研究,V类证据经验性研究Cooketal.,Chest,1992;102:
305S-311S急性缺血性卒中溶栓治疗概述静脉溶栓组织纤溶酶原激活物(tPA)NINDSECASSI&II,ATLANTIS链激酶MAST-I,MAST-E,ASK动脉溶栓前循环:
大脑中动脉(PROACTII)后循环:
基底动脉与安慰剂相比,3h内IVrtPA(0.9mg/kg)能改善90天时的预后出血发生率为6.4%,安慰剂为0.6%,但死亡率无差异所有亚组预后均优于安慰剂组益处可持续1年rt-PA:
NINDS随机,多中心,双盲,安慰剂对照620例;排除CT早期梗塞灶(预后不良)干预rtPA(1.1mg/kg)vs.placebo起病6h内主要终点BarthelIndexandmodifiedRankinScaleat90daysrtPA与安慰剂组无明显差别rt-PA:
ECASSIHackeetal.,JAMA.1995;274:
1017-1025随机,多中心,双盲,安慰剂对照800例;排除CT早期明显梗塞灶干预rtPA(0.9mg/kg)vs.placebo起病6h内主要终点modifiedRankinScaleScoreof1at90daysrtPA与安慰剂组无明显差别rt-PA:
ECASSIIHackeetal.,Lancet.1998;352:
1245-1251随机,多中心,双盲,安慰剂对照613例干预rtPA(0.9mg/kg)vs.placebo起病3-5h内主要终点NIHSSof1at90daysrtPA与安慰剂组无明显差别rt-PA:
ATLANTISAlteplaseThrombolysisforAcuteNoninterventionalRxinIschStrokeClarketal.,JAMA.1999;282:
2019-2026rt-PA:
小结与安慰剂相比,3h内IVrtPA(0.9mg/kg)能改善90天时的预后.I类证据目前证据显示,超过3h予IVtPA无效.I类证据链激酶(SK)提前终止;治疗窗4h无明显益处,结果不良4h1.5MUSKAustralianStreptokinaseTrial(ASK)Donnanetal.,Lancet1995;345:
578-9SK组,尤其是SK+aspirin组出血和死亡率高提前终止试验6h1.5MU300mg/dSKaspirinMulticenterAcuteStrokeTrial-Italy(MAST-I)Lancet1995;346:
1509-14SK组出血和死亡率高提前终止试验6h1.5MUSKMulticenterAcuteStrokeTrial-Europe(MAST-E)NEJM1996;335:
145-50结果治疗窗剂量药物研究与安慰剂相比,6h内予IVSK1.5MU预后不良(出血和死亡率高).I类证据动脉溶栓前循环大脑中动脉阻塞后循环椎基底动脉阻塞与安慰剂相比,6h内予IAProUK经造影证实MCAM1或M2段阻塞的患者有效.I类证据15%绝对有效(numberneededtotreat=7)增加颅内出血,死亡率无差异PROACTII:
小结急性椎基底动脉阻塞数项病例报道(IV、V类证据)非随机化无对照组Brandtetal.,CerebrovascDis,1995;5:
182-7小结3h内静脉用tPA能降低90天时的残障功能.I类证据静脉用链激酶(1.5MU)增加出血和死亡率.I类证据6h内动脉用尿激酶前体(Pro-UK,未被FDA通过)能降低90天时的残障功能.I类证据有证据支持在急性椎基底动脉阻塞中应用动脉溶栓.IV、V类证据急性缺血性卒中抗凝治疗概述肝素LMWheparinLMWheparinoid-作用于抗凝血酶III(抑制凝血因子IIa,IXa,andXa)1effectonXareducedpltinteractionlongerhalf-lifesimplertoadministerlowerbleedingriskreducedeffectonIIaSummary:
trialresultsLMWHLMWHLMWHLMWHheparinoidHepscHepIVdrugnodifferencelargeartbetterat3mo?
1281TOASTnodifference1486TAISTdead/depat6mo308HKnodifference767FISSnodifferenceamongdoses404TOPASnodifference19,435ISTnodifference225CanadianresultsN各卒中亚型急性抗凝治疗房颤和心源性栓塞大动脉粥样硬化椎基底动脉阻塞TIA进展性卒中动脉夹层静脉血栓形成各卒中亚型急性抗凝治疗:
小结nodiff231830后循环nodiff28600夹层nodiff5501TIAnodiff20402进展性卒中1+/1-7902静脉血栓1+(?
)/3-13,28540大动脉硬化nodiff361821心源性栓塞resultsNsubgrpCCT小结急性期抗凝减少深静脉血栓和肺栓塞发生,不增加颅内出血几率.I类证据急性缺血性卒中阿司匹林治疗急性缺血性卒中阿司匹林治疗InternationalStrokeStrial(IST)ASA300mg/dx2wksbegunwithin48hrs9.4%0.6%4.6%3.9%NoASAN=97151.1%*Majorextracranialbleed9.0%Death3.7%Allrecurrentstroke2.8%*RecurrentischemicASAN=97202wkendpts*p.01ChineseAcuteStrokeTrial(CAST)Lancet1997;349:
1641ASA160mg/dx4wksbegunwithin48hrs3.9%0.6%3.4%2.1%PlaceboN=103200.8%*Majorextracranbleed3.3%*Death3.2%Allrecurrentstroke1.6%*RecurrentischemicASAN=103354wkendpts*p.05小结小结基于IST和CAST,阿司匹林在急性缺血性卒中后2-4周内,每1000例患者中有10人可减少死亡和复发。
非心源性卒中二级预防:
非心源性卒中二级预防:
抗栓治疗抗栓治疗概述抗血小板药Antiplatelet.阿司匹林Aspirin抵克立得(噻氯匹啶)Ticlid(Ticlopidine)波力维(氯吡格雷)Plavix(Clopidogrel)艾诺思Aggrenox(aspirin+extended-releasedipyridamole)Warfarinfornon-cardioembolicarterialstroke:
includinglargevesseldisease.抗磷脂抗体综合征(ASP).颈椎动脉夹层.Aspirin高剂量阿司匹林随机对照试验0*P(10.9)SorDeath24m68A253;P2521500mgSwedishCS19877-77*P(9.6)SorDeath25m59A101;P1021000mgDanishCS1983641*P(7.5)Fatal;nonfatalCInoTIAincluded36m63.5A198;P204990mgAICLA1983ASA+DP5NS*P(8.3)TIA,S24m59A29;P291500mgReuther19784-6to31%*P(7.6)TIA,S,death26m?
A144;P1391300mgCCSG1978ASA+SP3Sameasmedical*P(15.7)TIA,CI,RI,death?
60.3A65;P60650mgAITIA1977surgicalgroup220onlywithTIA.*P(15.7)TIA,CI,RI,death37m60.2A88;P901300mgAITIA1977Medicalgroup1%ofRRPrim.Endpointf/uAge#ofptsASAdoseStudy#*Riskofvascularevents(death,stroke,MI)inthecontrolgroup低剂量阿司匹林随机对照试验11%(NS)*P(7.3)TIA,S,MI,vasculardeath2558.9A150P15150-100DanishLow1988(postCEA)118%*P(15.8)S,deathorboth2466.7A1649P164950ESPS2416%*P(10.6)Sordeath3266.9A676P68475SALT1991315%vsP;NSbetweendoses*P(5.7)MajorS,MI,Vasc.Death4859.88158068141200300PlaceboUKTIA19912%inRRPrim.EndpointF/uAge#ofptsASAdoseinmg.Study#*Vascularevents(death,MI,stroke)inplacebo.*strokeinplaceboAntiplateletTrialists100,000ptsfrom145trials.Allantiplateletagentswereincluded.Clumpedallvasculareventstogether.Overalloddsreductionforvasculareventswas25%.ForptswithminorstrokeorTIA(18trials)antiplateletagentsledtooddsreductionof22%forvasculareventsand23%fornonfatalstroke.Didnotanswerquestionsaboutaspirindose.Usedoddsratioinsteadofrelativerisk.Usedallantiplateletagents.Isthereaconsensus.TheFDAreviewedtrialsofaspirinvsplacebo(includingESPS-2,SALT,andUK-TIAtrials)toreducetheriskofstrokeanddeathinpatientswithpriorTIAorstroke.“Thepositivefindingsatlowerdosages(eg,50,75,and300mgdaily),alongwiththehigherincidenceofsideeffectsexpectedatthehigherdosage(eg,1,300mgdaily),aresufficientreasontolowerthedosageofaspirinforsubjectswithTIAandischemicstroke.”For“ischemicstrokeandTIA:
50to325mgaspirinonceaday.Continuetherapyindefinitely.”FDA.FederalRegister.1998;63:
56802.TiclopidineTASSStudy:
Efficacy*3-yearstudyendpoints,N=3,069.EndpointStrokeStroke,MI,orvasculardeathRRR21%9%(P=0.024)Hassetal.NEnglJMed.1989;321:
501.Easton.InHassandEaston(eds).Ticlopidine,PlateletsandVascularDisease.NewYork:
Springer-Verlag;1993:
141.*Ticlopidine(250mgbid)vsASA(650mgbid).(NS)Ticlopidine(%)Aspirin(%)DiarrheaRashNauseaGastritis,ulcer,GIbleedingSevereneutropenia(ANC450/mm3)Cerebralhemorrhage20.4*11.9*11.12.10.9*0.69.85.210.26.0*0.00.7*P0.05TASSStudy:
SideEffectsAdaptedfromHassetal.NEnglJMed.1989;321:
501.ClopidogrilCAPRIEStudyEfficacyofClopidogrelvs.Aspirin(n=19,185)PrimaryOutcome:
MI,IschemicStroke,orVascularDeathMonthsofFollow-UpMonthsofFollow-UpCumulativeCumulativeEventRate(%)EventRate(%)00448812121616ClopidogrelClopidogrelAspirinAspirin00336699121215151818212124242727303033333636AspirinAspirin5.83%5.83%5.32%5.32%ClopidogrelClopidogrelEventRateperYearEventRateperYear*PP=0.043=0.043CAPRIESteeringCommittee.Lancet1996;348:
1329-1339.CAPRIESteeringCommittee.Lancet1996;348:
1329-1339.ARR=0.51NNT=1/0.005=196Clopidogrel(%)ASA(%)GIcomplaintsAnybleedingdisorderRashDiarrheaGIbleedingIntracranialhemorrhage1.901.200.90*0.420.520.212.41*1.370.410.270.93*0.33*P0.05CAPRIESteeringCommittee.CAPRIESteeringCommittee.LancetLancet.1996;348:
1329-1339.1996;348:
1329-1339.SideEffectscausingdiscontinuationofdrugCAPRIEStudyManagementofAtherothrombosiswithClopidogrelinHigh-riskpatients(MATCH)氯吡格雷(75mg)+阿司匹林(75mg)与单用氯吡格雷(75mg)的疗效进行比较,结果是失败的两组的主要终点指标,即缺血性卒中、心肌梗死和血管源性死亡发生率与急性缺血事件(心绞痛、周围动脉症状恶化或TIA)无统计学差异联合治疗同时增加了严重出血的概率TheSecondEuropeanStrokePreventionStudy:
ESPS-2TestedefficacyofASA/ER-DPforsecondarystrokepreventionAddressedclinicalquestionsDoeslow-doseASApreventstroke?
DoesER-DPpreventstroke?
IsASA/ER-DPsuperiortoASAalone?
ToER-DPalone?
IsASA/ER-DPwelltolerated?
TheESPS-2Group.JNeurolSci.1997;151:
S3.Dieneretal.JNeurolSci.1996;143:
1.ESPS-2Results:
StrokeRatesat24MonthsPlaceboASAER-DPASA/ER-DP048121615.2%12.5%12.8%9.5%Incidence(%)ARR=5.7overPlaceboNNT=1/0.057=17.5ESPS-2:
SideEffectProfilePlaceboASAASA+EDGIEvent*28.1%30.4%32.8%Headache*32.3%33.1%38.1%Bleeding*4.5%8.2%8.7%(anysite)Lightheadedness30.9%29.1%29.5%*=P4mmLevelIII:
benefit34patientswithmobileatheromaLevelIII:
benefitFerrariEetalJACC1999;33:
1317-22主动脉弓粥样硬化TunickPetalAmJCardiol2002;90:
1320-5LevelIIIevidence:
benefitofstatins主动脉弓粥样硬化:
OACTunickPetalAmJCardiol2002;90:
1320-5LevelIIIevidence:
nobenefitofOAC主动脉弓粥样硬化:
APATunickPetalAmJCardiol2002;90:
1320-5LevelIIIevidence:
nobenefitofAPA主动脉弓粥样硬化:
他汀类TunickPetalAmJCardiol2002;90:
1320-5LevelIIIevidence:
benefitofstatins1strokepreventionRetrospectivedatashownobenefitofOACfornativevalveendocarditis,benefitforprostheticvalveendocarditis1-52strokeprevention:
Nodata感染性心内膜炎1DavenportetalStroke1990;21:
993-92PaschalisetalEurNeurol1990;30:
87-93YehetalCirculation1967;35:
I77-814DelahayeetalEurHeartJ1990;11:
1074-85WilsonetalCirculation1978;57:
1004-7LevelVevidence?
Pathogenesis:
fibrinthrombidepositsonvalvesassocwithcoagulopathy(usuallyDIC)Reportedincidenceofembolismvaries(14-91%)Rx:
Retrospectivedatasuggestbenefitofheparin,butnotOAC1-368%withrecurrentemboliwhenheparind/cdICHrisklowerthanininfectiveendocarditis1RogersetalAmJMed1987;83:
746-562LopezetalAmHeartJ1987;113:
773-843SacketalMedicine1977;56:
1-37非细菌性血栓性心内膜炎LevelVevidence:
nobenefitofOAC;benefitofheparininTrousseausyndrome(mainlywithDIC)EuropeanAtrialFibrillationTrial:
EAFT(Lancet1993;342:
1255-1262)Oralanticoagulants(225)vs.Aspirin(230)HR(95%CI)1Endpoint0.60(.41-.87)Allstroke0.38(.23-.64)Bleeding2.8(1.7-4.8)MajorbleedingOAC2.8%/yrvs.ASA0.9%/yrLevelIEvidence:
benefitofOACOptimumINRforpreventionof2strokeassociatedwithatrialfibrillation(EAFTNEJM1995;333:
5-10)“ThetargetvaluefortheINRshouldbesetat3.0”StrokePreventionwiththeORaldirectThrombinInhibitorinpatientswithnon-valvularatrialFibrillation(SPORTIF)SPORTIFIII是一项开放试验,SPORTIFV期是随机双盲多中心试验;比较了口服直接凝血酶抑制剂西美加群(ximelagatran)与华法林(INR23)对心房颤动罹患卒中的影响;两组预防缺血性卒中的疗效无统计学差异,华法林组并发出血的概率较高,西美加群组肝酶升高发生率为6%,比华法林组(0.8%)高很多,这也是尚未获得美国FDA批准的原因。
心肌梗死后一级预防:
短期抗凝Pre-thrombolyticeraHeparindecreasesstrokeincidence1-3Heparindecreasesmuralthrombus41MedResearchCouncilBMJ1969;1:
335-422Drapkin&MerskeyJAMA1972;222:
541-83VACoopStudyJAMA1973;225:
724-94Vaitkus&BarnathauJACC1993;22:
100-9心肌梗死后一级预防:
短期抗凝Post-thrombolyticerabaselineratesofdeath,reinfarction,strok
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