缺血性卒中抗栓循證治療(zhìliáo)共七十九頁證據(zhèngjù)等級I類證據

隨機對照試驗，

假陽性和假陰性(yīnxìng)錯誤低II類證據

隨機對照試驗，

假陽性和假陰性錯誤高III類證據

非隨機對列研究IV類證據

回顧性非隨機對列研究，V類證據

經驗性研究Cooketal.,Chest,1992;102:305S-311S共七十九頁急性(jíxìng)缺血性卒中溶栓治療共七十九頁概述(ɡàishù)靜脈(jìngmài)溶栓組織纖溶酶原激活物（tPA）

NINDSECASSI&II,ATLANTIS鏈激酶MAST-I,MAST-E,ASK動脈溶栓前循環:大腦中動脈(PROACTII)后循環:基底動脈

共七十九頁與安慰劑相比(xiānɡbǐ)，3h內IVrtPA(0.9mg/kg)能改善90天時的預后出血發生率為6.4%，安慰劑為0.6%，但死亡率無差異所有亞組預后均優于安慰劑組益處可持續1年rt-PA:NINDS共七十九頁隨機,多中心,雙盲,安慰劑對照620例;排除CT早期梗塞灶

(預后(yùhòu)不良)干預rtPA(1.1mg/kg)vs.placebo起病6h內主要終點BarthelIndexandmodifiedRankinScaleat90daysrtPA與安慰劑組無明顯差別rt-PA:

ECASSIHackeetal.,JAMA.1995;274:1017-1025共七十九頁隨機,多中心,雙盲,安慰劑對照800例;排除CT早期明顯梗塞灶

干預rtPA(0.9mg/kg)vs.placebo起病(qǐbìnɡ)6h內

主要終點modifiedRankinScaleScoreof≤1at90daysrtPA與安慰劑組無明顯差別rt-PA:

ECASSIIHackeetal.,Lancet.1998;352:1245-1251共七十九頁隨機,多中心,雙盲,安慰劑對照613例干預rtPA(0.9mg/kg)vs.placebo起病(qǐbìnɡ)3-5h內主要終點NIHSSof≤1at90daysrtPA與安慰劑組無明顯差別rt-PA:ATLANTIS

AlteplaseThrombolysisforAcuteNoninterventionalRxinIschStrokeClarketal.,JAMA.1999;282:2019-2026共七十九頁rt-PA:

小結(xiǎojié)與安慰劑相比，3h內IVrtPA(0.9mg/kg)能改善90天時的預后.I類證據目前證據顯示，超過(chāoguò)3h予IVtPA無效.I類證據共七十九頁鏈激酶（SK）

研究藥物劑量治療窗結果MulticenterAcuteStrokeTrial-Europe(MAST-E)NEJM1996;335:145-50SK1.5MU6hSK組出血和死亡率高提前終止試驗MulticenterAcuteStrokeTrial-Italy(MAST-I)Lancet1995;346:1509-14SKaspirin1.5MU300mg/d6hSK組，尤其是SK+aspirin組出血和死亡率高提前終止試驗AustralianStreptokinaseTrial(ASK)Donnanetal.,Lancet1995;345:578-9SK1.5MU4h提前終止;治療窗4h無明顯益處，結果不良與安慰劑相比，6h內予IVSK1.5MU預后(yùhòu)不良(出血和死亡率高).I類證據共七十九頁動脈(dòngmài)溶栓前循環大腦(dànǎo)中動脈阻塞后循環椎基底動脈阻塞共七十九頁與安慰劑相比,6h內予IAProUK經造影證實MCAM1

或M2

段阻塞的患者有效.I類證據15%絕對有效(numberneededtotreat=7)增加(zēngjiā)顱內出血，死亡率無差異PROACTII:

小結(xiǎojié)共七十九頁急性椎基底(jīdǐ)動脈阻塞數項病例報道(bàodào)(IV、V類證據)非隨機化無對照組

Brandtetal.,CerebrovascDis,1995;5:182-7

共七十九頁小結(xiǎojié)3h內靜脈用tPA能降低90天時的殘障功能.I類證據靜脈用鏈激酶(1.5MU)增加出血和死亡率.I類證據6h內動脈用尿激酶前體(Pro-UK,未被FDA通過(tōngguò))能降低90天時的殘障功能.I類證據有證據支持在急性椎基底動脈阻塞中應用動脈溶栓.IV、V類證據共七十九頁急性(jíxìng)缺血性卒中抗凝治療共七十九頁概述(ɡàishù)肝素(ɡānsù)LMWheparinLMWheparinoid- 作用于抗凝血酶III (抑制凝血因子IIa,IXa,andXa)

1

effectonXareducedpltinteractionlongerhalf-life

simplertoadministerlowerbleedingriskreducedeffectonIIa共七十九頁Summary:trialresultsNdrugresultsCanadian225HepIVnodifferenceIST19,435HepscnodifferenceTOAST1281heparinoidnodifferencelargeartbetterat3mo?HK308LMWH

dead/depat6moFISS767LMWHnodifferenceTAIST1486LMWHnodifferenceTOPAS404LMWHnodifferenceamongdoses共七十九頁各卒中亞型急性(jíxìng)抗凝治療

房顫

和心源性栓塞大動脈粥樣硬化椎基底(jīdǐ)動脈阻塞

TIA進展性卒中動脈夾層靜脈血栓形成共七十九頁各卒中亞型急性抗凝治療(zhìliáo):小結CCTsubgrpNresults心源性栓塞123618nodiff大動脈硬化0413,2851+(?)/3-后循環032318nodiffTIA1055nodiff進展性卒中20204nodiff夾層00286nodiff靜脈血栓20791+/1-共七十九頁小結(xiǎojié)

急性期抗凝減少深靜脈(jìngmài)血栓和肺栓塞發生，不增加顱內出血幾率.I類證據

共七十九頁急性缺血性卒中阿司匹林(āsīpǐlín)治療共七十九頁

InternationalStrokeStrial(IST)ASA300mg/dx2wksbegunwithin48hrs2wkendptsASAN=9720NoASAN=9715Recurrentischemic2.8%*3.9%Allrecurrentstroke3.7%4.6%Majorextracranialbleed1.1%*0.6%Death9.0%9.4%*p<.01共七十九頁ChineseAcuteStrokeTrial(CAST)

Lancet1997;349:1641ASA160mg/dx4wksbegunwithin48hrs4wkendptsASAN=10335PlaceboN=10320Recurrentischemic1.6%*2.1%Allrecurrentstroke3.2%3.4%Majorextracranbleed0.8%*0.6%Death3.3%*3.9%*p<.05共七十九頁小結(xiǎojié)

基于IST和CAST,阿司匹林在急性缺血性卒中后2-4周內，每1000例患者中有10人可減少(jiǎnshǎo)死亡和復發。共七十九頁非心源性卒中二級預防(yùfáng)：

抗栓治療共七十九頁概述(ɡàishù)抗血小板藥Antiplatelet.阿司匹林Aspirin抵克立得（噻氯匹啶）Ticlid?(Ticlopidine)波力維（氯吡格雷）Plavix?(Clopidogrel)艾諾思Aggrenox?(aspirin+extended-releasedipyridamole)Warfarinfornon-cardioembolicarterialstroke:includinglargevesseldisease.抗磷脂抗體綜合征（ASP）.頸椎動脈(dòngmài)夾層.共七十九頁Aspirin共七十九頁高劑量(jìliàng)阿司匹林隨機對照試驗#StudyASAdose#ofptsAgef/uPrim.Endpoint%ofRR1AITIA1977Medicalgroup1300mgA88;P9060.237mTIA,CI,RI,death20onlywithTIA.*P(15.7)2AITIA1977surgicalgroup650mgA65;P6060.3?TIA,CI,RI,deathSameasmedical*P(15.7)3CCSG1978ASA+SP1300mgA144;P139?26mTIA,S,death-6to31%*P(7.6)4Reuther19781500mgA29;P295924mTIA,SNS*P(8.3)5AICLA1983ASA+DP990mgA198;P20463.536mFatal;nonfatalCInoTIAincluded41*P(7.5)6DanishCS19831000mgA101;P1025925mSorDeath-77*P(9.6)7SwedishCS19871500mgA253;P2526824mSorDeath0*P(10.9)*Riskofvascularevents(death,stroke,MI)inthecontrolgroup共七十九頁低劑量阿司匹林(āsīpǐlín)隨機對照試驗#StudyASAdoseinmg.#ofptsAgeF/uPrim.Endpoint%inRR1DanishLow1988(postCEA)50-100A150P15158.925TIA,S,MI,vasculardeath11%(NS)*P(7.3)2UKTIA19911200300Placebo81580681459.848MajorS,MI,Vasc.Death

15%vsP;NSbetweendoses*P(5.7)3SALT199175A676P68466.932Sordeath16%*P(10.6)4ESPS250A1649P164966.724S,deathorboth18%**P(15.8)*Vascularevents(death,MI,stroke)inplacebo.**strokeinplacebo共七十九頁AntiplateletTrialists’100,000ptsfrom145trials.Allantiplateletagentswereincluded.Clumpedallvasculareventstogether.Overalloddsreductionforvasculareventswas25%.ForptswithminorstrokeorTIA(18trials)antiplateletagentsledtooddsreductionof22%forvasculareventsand23%fornonfatalstroke.Didnotanswerquestionsaboutaspirindose.Usedoddsratioinsteadofrelativerisk.Usedallantiplateletagents.共七十九頁Isthereaconsensus.

TheFDAreviewedtrialsofaspirinvsplacebo

(includingESPS-2,SALT,andUK-TIAtrials)toreducetheriskofstrokeanddeathinpatientswithpriorTIAorstroke.“Thepositivefindingsatlowerdosages

(eg,50,75,and300mgdaily),alongwiththehigherincidenceofsideeffectsexpectedatthehigherdosage(eg,1,300mgdaily),

aresufficientreasontolowerthedosageofaspirinforsubjectswithTIAandischemicstroke.”For

“ischemicstrokeandTIA:50to325mg

[aspirin]onceaday.Continuetherapyindefinitely.”FDA.FederalRegister.1998;63:56802.共七十九頁Ticlopidine

共七十九頁TASSStudy:Efficacy*?3-yearstudyendpoints,N=3,069.Endpoint?StrokeStroke,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)共七十九頁Ticlopidine(%)Aspirin(%)DiarrheaRashNauseaGastritis,ulcer,GIbleedingSevereneutropenia

(ANC<450/mm3)Cerebralhemorrhage20.4*11.9*11.12.10.9*0.69.85.210.26.0*0.00.7*P<0.05TASSStudy:SideEffectsAdaptedfromHassetal.NEnglJMed.1989;321:501.共七十九頁Clopidogril共七十九頁CAPRIEStudy

EfficacyofClopidogrelvs.Aspirin(n=19,185)PrimaryOutcome:MI,IschemicStroke,orVascularDeathMonthsofFollow-UpCumulative

EventRate(%)0481216ClopidogrelAspirin0369121518212427303336Aspirin5.83%5.32%ClopidogrelEventRateperYear*P=0.043CAPRIESteeringCommittee.Lancet1996;348:1329-1339.ARR=0.51NNT=1/0.005=196共七十九頁Clopidogrel(%)ASA(%)GIcomplaintsAnybleedingdisorderRashDiarrheaGIbleedingIntracranialhemorrhage1.901.200.90*0.420.520.212.41*1.370.410.270.93*0.33*P<0.05CAPRIESteeringCommittee.Lancet.1996;348:1329-1339.SideEffectscausingdiscontinuationofdrugCAPRIEStudy共七十九頁ManagementofAtherothrombosiswithClopidogrelinHigh-riskpatients（MATCH）

氯吡格雷（75mg）+阿司匹林（75mg）與單用氯吡格雷（75mg）的療效進行比較，結果是失敗的兩組的主要終點指標，即缺血性卒中、心肌梗死和血管源性死亡發生率與急性缺血事件（心絞痛、周圍動脈癥狀(zhèngzhuàng)惡化或TIA）無統計學差異聯合治療同時增加了嚴重出血的概率共七十九頁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.共七十九頁ESPS-2Results:

StrokeRatesat24MonthsPlaceboASAER-DPASA/ER-DP048121615.2%12.5%12.8%9.5%Incidence(%)ARR=5.7overPlaceboNNT=1/0.057=17.5共七十九頁ESPS-2:SideEffectProfile

Placebo ASA ASA+EDGIEvent* 28.1% 30.4% 32.8%Headache* 32.3% 33.1% 38.1%Bleeding* 4.5% 8.2% 8.7%(anysite)Lightheadedness

30.9% 29.1% 29.5% *=P<0.05共七十九頁Meta-Analysis:ASA/DPvsASAAdaptedfromDiener.Neurology.1998;51(suppl3):S17.TrialsToulouseTIA(N=284)AICLA(N=400)ACCSG(N=890)ESPS-2(N=3,299)Overall(N=4,873)15%RRRRelativeRisk(ofstroke,MI,orvasculardeath)0.511.522.53ASA/DPBetterASABetter共七十九頁PreventionRegimenforEffectivelyAvoidingSecondStrokes（PRoFESS）

是由30個國家參入，納入18500例患者(huànzhě)，為期4年的隨機雙盲多中心試驗，直接比較艾諾思Aggrenox（雙嘧達莫緩釋劑200mg+阿司匹林25mg，ER-DP200mg+ASA25mg，2次/d）與氯吡格雷（75mg，1次/d）在卒中二級預防中的療效，預期結果將在2008年報道。共七十九頁Warfarin-AspirinRecurrentStrokeStudy（WARSS）2206patientsfollowedfor2years

ISorDeath Mjrbleed/100pt-yrsWarfarin 17.8%2.22Aspirin 16.0%1.49p=.25Nosignificantdifferencebetweenwarfarinandaspirin共七十九頁TheWarfarin-AspirinSymptomaticIntracranialDiseasestudy（WASID）

多中心前瞻性隨機(suíjī)雙盲試驗華法林INR為2~3，阿司匹林為1300mg兩組的卒中發生率和血管源性病死率無統計學差異華法林組出血并發癥的發生率較高促使試驗提前終止

TheWarfarin-AspirinSymptomaticIntracranialDiseaseStudy.

Neurology.1995Aug;45(8):1488-93.共七十九頁EffectofTreatmentonRecurrentIschemicStrokeandDeathAtTwoYearsinAPASS/WARSS

(Brey,RL:presentedatthe27InternationalStrokeConference,SanAntonio,TX,February9,2002)PrimaryEndpoint(%)抗磷脂(línzhī)抗體陽性組與陰性組無差異，阿司匹林與華法林無差異

共七十九頁頸動脈和椎動脈夾層(jiācéng)Naturalhistoryofcarotiddissection:(HartetalNeurolClinNorthAm1:155,1983)Cerebralinfarctionin33%(23%minor,10%majororfatal.TIAin45;Headandneckpainin16%;Pulsatiletinnitus4%;andbruitin2%.Propermanagementiscontroversial.Mostptsdowell,eitherbecauseofordespitetreatment.共七十九頁

心源性卒中預防(yùfáng)：

抗血栓治療共七十九頁心源性卒中可能(kěnéng)病因Valvularheartdisease心臟(xīnzàng)瓣膜病Rheumaticmitralvalvedisease風濕性二尖瓣病Prostheticheartvalves人工心臟瓣膜Mitralvalveprolapse二尖瓣脫垂Aorticvalvedisease主動脈瓣病Aorticarchatherosclerosis主動脈弓粥樣硬化Endocarditis(infectiveornonbacterialthrombotic)心內膜炎（感染性或非細菌性血栓）Atrialfibrillation心房顫動Myocardialinfarction心肌梗死Leftventriculardysfunction左心室功能不全Patentforamenovale卵圓孔未閉共七十九頁Rheumaticmitralvalvedisease:

2°strokepreventionNorandomizedtrialsObservationalstudies:OACreducerecurrentembolicevents/fataleventsby2/3ormore1-3Extrapolationfrom1largerandomizedstudyinNVAF(EAFT)providesadditionaldataforpatientswithRHD+AF(butRHDexcluded)1SzekelyPBMJ1964;1:209-12

2AdamsGFetalJNNP1974;37:378-833Fleming&BaileyPostgradMed1971;47:599-604LevelIII-IV:BenefitofOAC共七十九頁Prostheticheartvalves:mechanicalvalves

1°strokepreventionObservationaldata:APAmaybesufficienttopreventembolisminabsenceofAF,butOACneededtopreventvalvethrombosis1-2RCT:additionofASA100mgtowarfarin(INR3-4.5)

cerebralembolism(4/186vs.12/184)3NonRCT:additionofASA500mgtripledriskofmajorhemorrhage(14%vs.5%)4

LevelIevidence:benefitofOAC+ASAoverOACalone1HartzRetalJThoracCVSurg1986;92:684-902RibeiroPetalJThoracCVSurg1986;91:92-83TurpieAetalNEJM1993;329:524-94ChesebroJetalAmJCard1983;51:1537-41共七十九頁Prostheticheartvalves:mechanicalvalves

2°strokepreventionNodirectdataACCPrecommendations:OAC+babyASAbasedonextrapolationof1°preventiondata6thACCPConsensusConferenceonAntithromboticTherapy2001共七十九頁Prostheticheartvalves:

bioprostheticvalves1NunezetalAnnThoracSurg1982;33:354-8ButnodifferenceinembolicratewithOAC(4.6%,7/260)incomparisontoASA(3.7%,5/135),andsignificantlyhigherrateofhemorrhagiccomplications(5.5%vs.0.4%)1

(Interestingly,lowrateoflateembolisminptswithAFdespitelackofchronicACinbothofthesestudies1°prevention:

LevelIVevidence:benefitofearlyOACovernoOACLevelVevidence:nodifferencebetweenOAC&ASA2°prevention:noevidence共七十九頁MitralValveProlapse:2°strokepreventionLevelVevidence:neitherASAnorACcompletelyeffectiveNwarfarinASANoRxWatson19791110/21/9Hanson19802221/40/120/6StrokerecurrenceinMVP:caseseriesMVP+AF:extrapolatedatafromEAFT1WatsonRTNeurol1979;29:886-92HansonMetalStroke1980;11:499-506共七十九頁Atherosclerosisofthethoracicaorta:

benefitofOAC50patientswithatheroma>4mmLevelIII:benefit34patientswithmobileatheromaLevelIII:benefitFerrariEetalJACC1999;33:1317-22共七十九頁主動脈弓(zhǔdòngmàigōng)粥樣硬化

TunickPetalAmJCardiol2002;90:1320-5LevelIIIevidence:benefitofstatins共七十九頁主動脈弓(zhǔdòngmàigōng)粥樣硬化:OAC

TunickPetalAmJCardiol2002;90:1320-5LevelIIIevidence:nobenefitofOAC共七十九頁主動脈弓(zhǔdòngmàigōng)粥樣硬化:APA

TunickPetalAmJCardiol2002;90:1320-5LevelIIIevidence:nobenefitofAPA共七十九頁主動脈弓(zhǔdòngmàigōng)粥樣硬化:他汀類

TunickPetalAmJCardiol2002;90:1320-5LevelIIIevidence:benefitofstatins共七十九頁1°strokepreventionRetrospectivedatashownobenefitofOACfornativevalveendocarditis,benefitforprostheticvalveendocarditis1-52°strokeprevention:Nodata感染性心內膜炎1DavenportetalStroke1990;21:993-92PaschalisetalEurNeurol1990;30:87-93YehetalCirculation1967;35:I77-814DelahayeetalEurHeartJ1990;11:1074-85WilsonetalCirculation1978;57:1004-7LevelVevidence共七十九頁?Pathogenesis:fibrinthrombidepositsonvalvesassocwithcoagulopathy(usuallyDIC)Reportedincidenceofembolismvaries(14-91%)Rx:Retrospectivedatasuggestbenefitofheparin,butnotOAC1-368%withrecurrentemboliwhenheparind/c’dICHrisklowerthanininfectiveendocarditis1RogersetalAmJMed1987;83:746-562LopezetalAmHeartJ1987;113:773-843SacketalMedicine1977;56:1-37非細菌性血栓性心內膜炎LevelVevidence:nobenefitofOAC;benefitofheparininTrousseausyndrome(mainlywithDIC)共七十九頁EuropeanAtrialFibrillationTrial：EAFT

(Lancet1993;342:1255-1262)Oralanticoagulants(225)vs.Aspirin(230)

HR(95%CI)1°Endpoint 0.60(.41-.87)Allstroke 0.38(.23-.64)Bleeding 2.8(1.7-4.8)MajorbleedingOAC2.8%/yrvs.ASA0.9%/yr

LevelIEvidence:benefitofOAC共七十九頁OptimumINRforpreventionof2°strokeassociatedwithatrialfibrillation

(EAFTNEJM1995;333:5-10)“ThetargetvaluefortheINRshouldbesetat3.0”共七十九頁StrokePreventionwiththeORaldirectThrombinInhibitorinpatientswithnon-valvularatrialFibrillation(SPORTIF)

SPORTIFIII是一項開放試驗,SPORTIFV期是隨機雙盲多中心試驗；比較了口服直接凝血酶抑制劑西美加群（ximelagatran）與華法林（INR2~3）對心房顫動罹患卒中的影響；兩組預防缺血性卒中的療效無統計學差異，華法林組并發出血的概率(gàilǜ)較高，西美加群組肝酶升高發生率為6%，比華法林組（0.8%）高很多，這也是尚未獲得美國FDA批準的原因。共七十九頁心肌梗死(xīnjīɡěnɡsǐ)后一級預防:短期抗凝Pre-thrombolyticeraHeparindecreasesstrokeincidence1-3Heparindecreasesmuralthrombus41MedResearchCouncilBMJ1969;1:335-422Drapkin&MerskeyJAMA1972;222:541-83VACoopStudyJAMA1973;225:724-94Vaitkus&BarnathauJACC1993;22:100-9共七十九頁心肌梗死(xīnjīɡěnɡsǐ)后一級預防:短期抗凝Post-thrombolyticerabaselineratesofdeath,reinfarction,stroke,&PEmarkedlylowerwiththrombolytics&ASAadditionofheparin/LMWHmaydecreasemuralthrombusformation,butincreasesriskofmajorbleedingwithoutfurtherreducingstrokerisk1CollinsetalBMJ1996;313:652-92CollinsetalNEJM1997;336:847-603FRAMIKontnyetalJACC1997;30:962-94SCATILancet1989;2:182-65Gissi-2VecchioetalCirculation1991;84:512-9共七十九頁心肌梗死(xīnjīɡěnɡsǐ)后一級預防:長期抗凝Relativetocontrol,coumarinsinmoderateorhighdose(INR2-4.8)SignificantlydecreasestrokeincidenceSignificantlyincreaseincidenceofmajorbleedingAnand&YusufJAMA1999;282:2058-67共七十九頁ModifiedfromAnand&YusufJAMA1999;282:2058-67…ButnobenefitrelativetoASAIncidenceofstrokeandsignificantincreaseinmajorbleeding共七十九頁

RR(95%CI)Anticoagulation*.19(.13-.27)Aspirin# .44(.29-.65)

LevelIIIevidence:benefitofAC>ASAfor1°prevention左心室功能不全:

卒中危險因子多變量(biànliàng)分析

(LohEetalNEJM1997;336:251-257)*

similar

riskatalllevelsofEF<40%#similar

riskatalllevelsofEF<35%共七十九頁

Rate(Events/100Pt-Yr)Anticoagulation 0(0/40)NoAnticoagulation 0.35(1/288)

LowRiskforPrimaryOccurrence慢性室壁瘤系統(xìtǒng)栓塞

(LapeyreACetalJACC1985;6:534-538)共七十九頁PatentForamenOvaleinCryptogenicStrokeStudy(PICSS)

(HommaSetalCirculation2002;105:2625-31)Design:Prospective,randomized,double-blind,multi-centerclinicaltrialEligibility:EnrolledinWARSSAgreetohaveadditionalTEETreatment:Warfarin(targetINR1.4-2.8,mean2.1)vs.aspirin325mg1°endpoint:Recurrentischemicstrokeordeathwithin2years601patients42%withcryptogenicstrokeasqualifyingevent34%withPFO共七十九頁PICSSLevelIIEvidence:NodifferencefromaspirinoverallorinanysubgroupNoincreasedeventrateinPFO+ASAvs.PFOonlyNoincreasedratewithlargerPFOsize共七十九頁RheumaticMVdz:LevelIII

-BenefitovernoOACAorticarchatheroma:Level

III

-BenefitoverAPAin1study;NobenefitofOACorAPAinanother(butbenefitofstatins)Infectiveendocarditis:Nativevalve:LevelV-NobenefitProstheticvalve:LevelV-

benefitNBTE:LevelV-Nobenefit

(?benefitofheparin)Atrialfibrillation:

Level

I

-BenefitoverASA[INR2.9(2.5-4.0)]PFO:

LevelII

-NobenefitoverASA(INR1.4–2.8)MVP:

LevelV

–NotcompletelyeffectiveAtrialfibrillation:

LevelI

-BenefitoverASA[INR2.9(2.5-4.0)]

PFO:

Leve