抗血小板治疗出血风险控制课件.ppt

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1、抗血小板治抗血小板治疗出血出血风险控制控制抗血小板治疗药物的演变氯吡格雷氯吡格雷氯吡格雷氯吡格雷噻氯匹定噻氯匹定阿司匹林阿司匹林l1988年FDA批准用于临床的抗血小板药物l单用疗效有限，增加剂量会增加出血危险l第一个噻吩吡啶类l 1991年FDA批准l 严重不良反应：中性粒细胞减少、血栓性血小板减少性紫癜l 1998 1998年年FDAFDA批准批准l 疗效、安全性被广泛证实疗效、安全性被广泛证实*普拉格雷普拉格雷*替格瑞洛替格瑞洛当代抗血小板当代抗血小板当代抗血小板当代抗血小板药药物治物治物治物治疗疗的的的的发发展：缺血与出血展：缺血与出血展：缺血与出血展：缺血与出血风险风险的平衡的平衡的

2、平衡的平衡抗血小板抗血小板抗血小板抗血小板药药物物物物单药单药治治治治疗疗双双双双联联抗血小板抗血小板抗血小板抗血小板药药物物物物更更更更强强的血小板聚集抑制的血小板聚集抑制的血小板聚集抑制的血小板聚集抑制剂剂ReductioninReductioninIschemicIschemicEventsEventsIncreaseinIncreaseinMajorBleedsMajorBleedsAdaptedfromAdaptedfromGibson,AHA2007Gibson,AHA2007氯吡格雷吡格雷+ASA双双联治治疗12个月，个月，显著降低著降低NSTE-ACS患者缺血患者缺血风险达达2

3、0%安全性：波立维组与安慰剂组危及生命的大出血无显著差异。YusufS,ZhaoF,MehtaSR,etal.NEnglJMed.2001;345(7):494-502.NSTE-ACSNSTE-ACS患者患者患者患者应应用用用用氯氯吡格雷吡格雷吡格雷吡格雷+ASA+ASA安全性良好安全性良好安全性良好安全性良好TheCUREtrialinvestigators.NEngJMed.2001;345(7):494-502.uCURE研究表明，与安慰剂+ASA相比，氯吡格雷+ASA导致危及生命出血或出血导致死亡的发生率无明显增加TRITON-TIMI38研究：普拉格雷的研究：普拉格雷的总体体疗效与

4、安全性效与安全性WiviottSD,BraunwaldE,McCabeCH,etal.NEnglJMed.2007;357:2001-15.事件率()CV死亡/MI/卒中CV死亡非致死性MI非致死性卒中(P0.001)(P=0.31)(P0.001)(P=0.93)RRR=19%RRR=24%疗效：普拉格雷显著降低15个月CV死亡/MI/卒中风险(主要缺血终点)达19%；获益主要源于非致死性MI的降低。TIMI大出血危及生命出血非致命性出血致命性出血颅内出血出血率()(P=0.002)(P=0.03)(P=0.01)(P=0.23)(P=0.74)RRI=319%RRI=32%RRI=52%氯

5、吡格雷普拉格雷出血：普拉格雷显著增加非CABG相关TIMI大出血风险(主要安全终点)达32%；包括危及生命、致命性出血等。（非CABG相关出血）替格瑞洛显著降低ACS患者心血管事件发生危险达16%PLATO研究中替格瑞洛组平均用药时间277天，替格瑞洛显著降低CV死亡、MI或卒中复合终点发生危险16%Daysafterrandomisation060120180240300360121110987654321013累累积发生率积发生率(%)9.811.7HR0.84(95%CI0.770.92),p=0.0003ClopidogrelTicagrelor然而，代价是非CABG相关的大出血风险明

6、显升高。70K-Mestimatedrate(%peryear)98654321Non-CABGPLATOmajorbleeding4.53.8p=0.032.82.2p=0.037.47.9NS5.35.8NSTicagrelorClopidogrelNon-CABGTIMImajorbleedingCABGPLATOmajorbleedingCABGTIMImajorbleedingWallentin L et al.New Engl J Med.2009;361:DOI:10.1056/NEJMoa0904327.一旦出血，无论大小，都很麻烦小出血小出血临床常床常见，显著降低患者治著降低

7、患者治疗依从性依从性ACS患者(n=396)成功置入支架，接受ASA+普拉格雷1个月1个月内普拉格雷总停药率个月内普拉格雷总停药率6%*滋扰性出血滋扰性出血63%内出血内出血33.3%令人惊恐的出血3.7%1个月内总体出血发生率个月内总体出血发生率13.6%采用Roys出血分类及定义：令人惊恐的出血：颅内出血、危及生命出血或需输血。内出血：血肿、鼻衄、口腔出血、阴道出血、黑便、眼睛出血、血尿及呕血。滋扰性出血：容易瘀伤、小切口出血、瘀点及瘀斑。小出血=滋扰性或内出血因滋扰性出血或因滋扰性出血或内出血停药内出血停药其他原因其他原因停药停药15.3%4%P=0.03*79%为患者自发停药出血后过早

8、停用抗血小板治疗是影响临床结局的重要因素32.4%发生院内出血，其中近1/10出院后停用任何抗血小板药物：出院后停用抗血小板药物显著增加6个月死亡/MI/卒中风险(14.3%vs用药者7.8%，P0.0001)N=26,451，入选自PURSUIT,PARAGON A&B，SYNERGYPCI亚组分析：过早停用抗血小板治疗对院内PCI患者长期预后更具危险性双联抗血小板治疗显著减少死亡等主要临床终点事件AmHeartJ.2010;160:1056-1064.e2.logrankp-valueforallfourcategories0.0001log-rankp-valuefornobleedin

9、gvs.mildbleeding=0.02log-rankp-valueformildvs.moderatebleeding0.0001log-rankp-valueformoderatevs.severe31天0.512481632HR(95%CI)死亡P值0.0010.0010.0010.120.0010.0010.0010.0010.0010.0010.00131天输血0-1天2-7天8-30天31天HR(95%CI)ACUITY研究中，对于ACS患者远期死亡的作用再发MI：随时间而减弱，30天已无显著性大出血和输血：存在持续影响，1年时仍具显著性对ACS患者远期结局的持续影响大出血/输

10、血的影响更甚于缺血EurHeartJ.2009;30:1457-1466.如何评估出血风险？出血评估的有效工具出台CRUSADE出血评分CRUSADE出血评分计算器（可从获得）Circulation2009;119;1873-1882缺血高危因素与出血高危因素大多一致缺血高危因素与出血高危因素大多一致HectorBueno,FranciscoFernandez-Aviles.Heart2012;98:162-168ACSACS缺血风险主要预测因素缺血风险主要预测因素ACSACS出血风险主要预测因素出血风险主要预测因素老年患者和肾功能不全等特殊人群老年患者和肾功能不全等特殊人群临床治疗尤其应重视

11、出血与缺血平衡临床治疗尤其应重视出血与缺血平衡抗血小板治疗时，如何减少出血风险？其它抗血小板药物？(cilostazol,vorapaxar,cangrelor)调整DAPT持续时间？减少APT剂量？围PCI过程中，何种策略减少出血风险？消化道出血，加用PPI？抗血小板治疗时，如何减少出血风险？其它抗血小板药物？(cilostazol,vorapaxar,cangrelor)调整DAPT持续时间？减少APT剂量？围PCI过程中，何种策略减少出血风险？CilostazolvsAsaparinCochraneDatabaseSystRev.2011Jan19;(1):CD008076.Cochra

12、neDatabaseSystRev.2011Jan19;(1):CD008076.CVEVENTSIschaemicstrokeCochraneDatabaseSystRev.2011Jan19;(1):CD008076.HaemorrhagicstrokeCochraneDatabaseSystRev.2011Jan19;(1):CD008076.MICochraneDatabaseSystRev.2011Jan19;(1):CD008076.VasculardeathCochraneDatabaseSystRev.2011Jan19;(1):CD008076.Extracranialhae

13、morrhageCochraneDatabaseSystRev.2011Jan19;(1):CD008076.GIbleedingCochraneDatabaseSystRev.2011Jan19;(1):CD008076.Cilostazol+ASAvsASAAmericanHeartJournalJune2008RevascularizatinRestenosisConclusionforcilostazolNOstrongevidenceforCilostazolinCHDStrongerthanASA,maybeequivalenttoTICLIDDecreasebleedingNee

14、dmoredatetosupportitsuseinCHDanti-platelettherapyVorapaxarprotease-activatedreceptor1antagonistTwolargescaleRCTresultspublishedOriginalArticleThrombin-ReceptorAntagonistVorapaxarinAcuteCoronarySyndromes(NSTEACS)PierluigiTricoci,M.D.,Ph.D.,ZhenHuang,M.S.,ClaesHeld,M.D.,Ph.D.,DavidJ.Moliterno,M.D.,Pau

15、lW.Armstrong,M.D.,FransVandeWerf,M.D.,HarveyD.White,D.Sc.,PhilipE.Aylward,M.D.,LarsWallentin,M.D.,Ph.D.,EdmondChen,M.D.,YuliyaLokhnygina,Ph.D.,JinglanPei,M.S.,SergioLeonardi,M.D.,TyrusL.Rorick,R.N.,AnnM.Kilian,B.S.,LisaH.K.Jennings,Ph.D.,GiuseppeAmbrosio,M.D.,Ph.D.,ChristophBode,M.D.,AngelCequier,M.

16、D.,JanH.Cornel,M.D.,RafaelDiaz,M.D.,AycanErkan,M.D.,Ph.D.,KurtHuber,M.D.,MichaelP.Hudson,M.D.,LixinJiang,M.D.,J.WouterJukema,M.D.,Ph.D.,BasilS.Lewis,M.D.,A.MichaelLincoff,M.D.,GillesMontalescot,M.D.,JosCarlosNicolau,M.D.,Ph.D.,HisaoOgawa,M.D.,MatthiasPfisterer,M.D.,JuanCarlosPrieto,M.D.,WitoldRuzyll

17、o,M.D.,PeterR.Sinnaeve,M.D.,Ph.D.,RobertF.Storey,M.D.,D.M.,MarcoValgimigli,M.D.,Ph.D.,DavidJ.Whellan,M.D.,PetrWidimsky,M.D.,Dr.Sc.,JohnStrony,M.D.,RobertA.Harrington,M.D.,KennethW.Mahaffey,M.D.,fortheTRACERInvestigatorsNEnglJMedVolume366(1):20-33January5,2012StudyOverviewInthistrial,vorapaxar,aprote

18、ase-activatedreceptor1antagonistthatinhibitsthrombin-inducedplateletactivation,wasnoteffectiveinreducingtheprimarycardiovascularefficacyendpoint,anditincreasedratesofbleeding,includingseriousbleedingandintracranialhemorrhage.StudyEndPoints.TricociPetal.NEnglJMed2012;366:20-33Theprimaryefficacyendpoi

19、ntwasacompositeofdeathfromcardiovascularcauses,myocardialinfarction,stroke,recurrentischemiawithrehospitalization,orurgentcoronaryrevascularization.Theprespecifiedkeysecondaryendpointwasacompositeofdeathfromcardiovascularcauses,myocardialinfarction,orstroke.EfficacyEndPoints.RiskofBleeding.TricociPe

20、tal.NEnglJMed2012;366:20-33BleedingEndPointsintheAs-TreatedPopulation.TricociPetal.NEnglJMed2012;366:20-33ConclusionsInpatientswithacutecoronarysyndromes(NSTEACS),theadditionofvorapaxartostandardtherapy(ASA+Thienopyridine)didnotsignificantlyreducetheprimarycompositeendpointbutsignificantlyincreasedt

21、heriskofmajorbleeding,includingintracranialhemorrhage.Circulation.132(20):1871-1879,November 17,2015.DOI:10.1161/CIRCULATIONAHA.114.015042background26449patientsover3yearspriorMI,strokeorperipheralvasculardiseaserandomizationtovorapaxarorplaceboinadditiontoASAorASA+Thienopyridine2BaselineCharacteris

22、ticsCharacterization of Actual Thienopyridine Use From RandomizationCardiovascular death,MI,or stroke stratified by planned thienopyridine useEfficacy end points stratified by planned thienopyridine useBleeding End Points Stratified by Planned Thienopyridine Use Safety end point stratified by planne

23、d thienopyridine useNet Clinical Outcome End Points Stratified by Planned Thienopyridine Use Among Patients With a Previous MI and No History of TIA or StrokeapprovedbytheFDAandEMAforreducingischaemiceventsinpatientswithahistoryofMIthebenefitofvorapaxarinadditiontoaspirinandclopidogrelismodestandmus

24、tbecarefullyweighedagainsttheincreaseinbleedingeventsItsuseiscontraindicatedinpatientswithahistoryofcerebrovasculardisease.FDA&EMA recommendationCangrelorVol382December14,2013IncludedstudiesVol382December14,2013均联合应用氯吡格雷均联合应用氯吡格雷+ASAEfficacyResultsVol382December14,2013Vol382December14,2013BleedingEv

25、entsVol382December14,2013Cangrelorreducedtheoddsofall-causedeath,myocardialinfarction,orischaemia-drivenrevascularisationnodifferenceintheprimarysafetyoutcome,inGUSTOmoderatebleedingincreasedGUSTOmildbleedingConclusion for Cangrelor抗血小板治疗时，如何减少出血风险？其它抗血小板药物？(cilostazol,vorapaxar,cangrelor)缩短DAPT持续时间

26、？减少药物剂量？围PCI过程中，何种策略减少出血风险？合并常规抗凝药物（房颤），如何处理？3months出血事件没有差别！6monthsCirculationJanuary24,20121yearfollow-up，nodifferenceinbleedingStillnodifferenceinbleedingfor1year1monthDurationofDAPTfor1monthJACCVOL.65,NO.8,2015ConclusionforshorteningDAPTDurationLogicallyreasonableNodirectevidenceyetESC2015NSTEAC

27、SguidelineEvidence？LoweringAPTdose？50mgvs75mgclopidogrel50mgvs75mgclopidogrelBecauseofsmallsamplesize,nodifferenceinbleedingTicagrelor60mgbidVS90mgbidPEGASUSStudy60mgvs90mg，略有减少？，略有减少？仅有仅有3年的数据结果，更短时间是否有差异呢？年的数据结果，更短时间是否有差异呢？ConclusionforloweringdosesLowerdosesmaydecreasebleedingNeedmoredatatosuppor

28、ttheefficacyandsafety抗血小板治疗时，如何减少出血风险？其它抗血小板药物？调整DAPT持续时间？降低药物剂量？围PCI过程中，何种策略减少出血风险？(radialaccess,bivaludin，fondaparinux)MATRIXCo-primarycompositeoutcomesat30daysN=8404NSTE-ACS+STEMIRadialvs.femoralValgimigliMetal.Lancet.2015;385:2465-76All-causemortality,MI,strokeAll-causemortality,MI,stroke,orBARC

29、3or5bleeding75SpeakerRadial vs femoral meta-analysisNon-CABGmajorbleeedsDeath,MI,orstrokeDeathMIStrokePRR(95%CI)ValgimigliMetal.Lancet.2015;385:2465-76N19000Radialapproach2015ESCNSTEACSGuidelineItisrecommendedthatcentrestreatingACSpatientsimplementatransitionfromtransfemoraltotransradialaccess.Profi

30、ciencyinthefemoralapproachshouldbemaintained(e.g.forIABPinsertionandstructuralaswellasperipheralprocedures)77比伐卢定的优势比伐卢定的优势u20个氨基酸的肽类药物，凝血酶的直接抑制剂个氨基酸的肽类药物，凝血酶的直接抑制剂u与凝血酶的结合过程可控可逆与凝血酶的结合过程可控可逆u血浓度与血浓度与APTT、PT和和ACT正相关正相关（r分别为分别为0.77、0.73和和0.8）u不需要抗凝血酶不需要抗凝血酶（AT-）作为辅助因子，量效关系更吻合）作为辅助因子，量效关系更吻合u对血栓中和循环中的

31、凝血酶的抑制作用几乎相同对血栓中和循环中的凝血酶的抑制作用几乎相同u不受激活血小板的影响不受激活血小板的影响u不减少血小板不减少血小板比伐卢定Vs肝素uACUITY试验-JAMA2007uREPLACE-2试验-TCT2008uISAR-REACT-4试验-AHA2011uEUROMAX试验-NEJM2013uHORIZONSAMI试验-NEJM2006，TCT2008Diff=Diff=0.0%-1.6,1.5 RR=0.99RR=0.990.76,1.30 P Psupsup=0.95=0.95Diff=Diff=-3.3%-5.0,-1.6 RR=RR=0.600.46,0.77P PN

32、INI0.00010.0001P Psupsup0.00010.0001Diff=Diff=-2.9%-4.9,-0.8RR=RR=0.760.63,0.92 P PNINI0.00010.0001P Psupsup=0.005=0.0051 endpoint1 endpointMajor2 endpointStoneGWetal.NEJM2008;358:2218-30HORIZONS AMI 试验试验3,602发病病12小小时的的STEMI患者患者3006例作支架分例作支架分组治治疗，30天天临床床结果果HORIZONSAMI试验试验3,602发病病12小小时的的STEMI患者患者3006

33、例作支架分例作支架分组治治疗，1年随年随访结果果1 年净临床不良事件年净临床不良事件TCT2008TCT2008HORIZONSAMI试验试验3,602发病病12小小时的的STEMI患者患者3006例作支架分例作支架分组治治疗，1年随年随访结果果TCT2008TCT2008HORIZONSAMI试验试验3,602发病病12小小时的的STEMI患者患者3006例作支架分例作支架分组治治疗，3年随年随访结果果TheLancet,Volume377,Issue9784,2011,2193-2204Major bleedingCardiac mortalityReinfarctionStent thr

34、ombosisAHA2013STEMIguidelineBivalirudin seems to be perfect!HoweverHEAT-PPCI研究掀起波澜研究掀起波澜HEAT-PPCI(Unfractionated Heparin versus Bivalirudin in Primary PCI)研究研究-开放、单中心、随机对照开放、单中心、随机对照Adeel Shahzad，ACC2014u英国利物浦心胸医院，英国利物浦心胸医院，14名介入医生参加，历时名介入医生参加，历时22个月个月u1812 例例STEMI患者随机分组患者随机分组u比伐卢定组比伐卢定组905例患者，例患者，7

35、51例例(83%)造影后造影后 行介入治疗；肝行介入治疗；肝素组素组 907 例患者，例患者，740例例(82%)行介入治疗行介入治疗u两组两组 GP IIb/IIIa 抑制剂应用率相似，约抑制剂应用率相似，约 13%u30天临床终点天临床终点uLancet.2014 Jul 4.pii:S0140-6736(14)60924-7.HEAT-PPCI30天临床终点OutcomeBivalirudin(%)Heparin(%)RR(95%CI)pMACE8.75.71.52(1.12.1)0.01Definiteorprobablestentthrombosis3.40.93.91(1.69.5

36、)0.001Majorbleeding3.53.1NSAdeel Shahzad，ACC2014对HEAT-PPCI的批评u单中心u入选速度（22个月近2000例患者）u肝素用量（70U/kg)uACT偏低（H-236，B-270)u入选患者低危u再梗的判断标准u研究设计-知情签署晚-伦理？u桡动脉途径比例高与出血低有关NAPLESIII研究Carlo Briguori(Clinica Mediterranea,Naples,Italy)，ACC2014u830例高出血风险（危险积分例高出血风险（危险积分10）择期股动脉）择期股动脉途径途径PCI患者患者u比伐卢定比伐卢定VsUFHu主要终点：

37、院内出血主要终点：院内出血u主要结果：按不同出血标准，两组均无差异主要结果：按不同出血标准，两组均无差异TCT2014BRIGHT研究StentThrombosisat30DaysEventBivalirudin(n=735),n(%)Heparin(n=729),n(%)Heparin+tirofiban,n(%)pAlldefinite/probablestentthrombosis4(0.6)6(0.9)5(0.7)0.77Acute(24h)2(0.3)2(0.3)2(0.3)1.00Subacute(130d)2(0.3)4(0.6)3(0.4)0.66TCT2014AHA2014N

38、STE-ACSguidelineRecommendationsforanticoagulationinNSTE-ACSRecommendationsClassLOEParenteralanticoagulationisrecommendedatthetimeofdiagnosisaccordingtobothischaemicandbleedingrisks.IBFondaparinux(2.5mgs.c.daily)isrecommendedashavingthemostfavourableefficacysafetyproofthemanagementstrategy.IBBivaliru

39、din(0.75 mg/kg i.v.bolus,followed by 1.75 mg/kg/hour for up to 4 hours after theprocedure)isrecommendedasalternativetoUFHplusGPIIb/IIIainhibitorsduringPCI.IAUFH70100IU/kgi.v.(5070IU/kgifconcomitantwithGPIIb/IIIainhibitors)isrecommendedinpatientsundergoingPCIwhodidnotreceiveanyanticoagulant.IBInpatie

40、ntsonfondaparinux(2.5mgs.c.daily.)undergoingPCI,asinglei.v.bolusofUFH(7085IU/kg,or5060IU/kg in thecaseof concomitantuseof GPIIb/IIIainhibitors)is recommendedduringtheprocedure.IBEnoxaparin(1 mg/kg s.c.twice daily)or UFH are recommended when fondaparinux is notavailable.IBCrossoverbetweenUFHandLMWHis

41、notrecommended.IIIBInNSTEMIpatientswithnopriorstroke/TIAandathighischaemicriskaswellaslowbleedingriskreceivingaspirinandclopidogrel,low-doserivaroxaban(2.5mgtwicedailyforapproximatelyoneyear)maybeconsideredafterdiscontinuationofparenteralanticoagulation.IIbBESC2015NSTE-ACSguidelineFondaparinuxCompar

42、isonofFondaparinuxandEnoxaparininAcuteCoronarySyndromes（NSTEACS）TheFifthOrganizationtoAssessStrategiesinAcuteIschemicSyndromesInvestigatorsNEnglJMedVolume354;14:1464-1476April6,2006CumulativeRisksofDeath,MyocardialInfarction,orRefractoryIschemia(PanelA)andofMajorBleeding(PanelB)throughDay9TheFifthOr

43、ganizationtoAssessStrategiesinAcuteIschemicSyndromesInvestigatorsNEnglJMed2006;354:1464-1476MainEfficacyandSafetyOutcomesTheFifthOrganizationtoAssessStrategiesinAcuteIschemicSyndromesInvestigatorsNEnglJMed2006;354:1464-1476CumulativeRisksofDeath(PanelA)andofDeath,MyocardialInfarction,orStroke(PanelB

44、)throughDay180TheFifthOrganizationtoAssessStrategiesinAcuteIschemicSyndromesInvestigatorsNEnglJMed2006;354:1464-1476ResultsofSubgroupAnalysesofEfficacy(theCompositeofDeath,MyocardialInfarction,orRefractoryIschemia)(PanelA)andSafety(MajorBleeding)(PanelB)atNineDaysTheFifthOrganizationtoAssessStrategi

45、esinAcuteIschemicSyndromesInvestigatorsNEnglJMed2006;354:1464-1476Treatments,Complications,andOutcomesamongPatientsUndergoingPercutaneousCoronaryIntervention(PCI)withintheFirstEightDaysafterRandomizationTheFifthOrganizationtoAssessStrategiesinAcuteIschemicSyndromesInvestigatorsNEnglJMed2006;354:1464

46、-1476ConclusionFondaparinuxissimilartoenoxaparininreducingtheriskofischemiceventsatninedays,butitsubstantiallyreducesmajorbleedingandimproveslongtermmortalityandmorbidityRecommendationsforanticoagulationinNSTE-ACSRecommendationsClassLOEParenteralanticoagulationisrecommendedatthetimeofdiagnosisaccord

47、ingtobothischaemicandbleedingrisks.IBFondaparinux(2.5mgs.c.daily)isrecommendedashavingthemostfavourableefficacysafetyproofthemanagementstrategy.IBBivalirudin(0.75 mg/kg i.v.bolus,followed by 1.75 mg/kg/hour for up to 4 hours after theprocedure)isrecommendedasalternativetoUFHplusGPIIb/IIIainhibitorsd

48、uringPCI.IAUFH70100IU/kgi.v.(5070IU/kgifconcomitantwithGPIIb/IIIainhibitors)isrecommendedinpatientsundergoingPCIwhodidnotreceiveanyanticoagulant.IBInpatientsonfondaparinux(2.5mgs.c.daily.)undergoingPCI,asinglei.v.bolusofUFH(7085IU/kg,or5060IU/kg in thecaseof concomitantuseof GPIIb/IIIainhibitors)is

49、recommendedduringtheprocedure.IBEnoxaparin(1 mg/kg s.c.twice daily)or UFH are recommended when fondaparinux is notavailable.IBCrossoverbetweenUFHandLMWHisnotrecommended.IIIBInNSTEMIpatientswithnopriorstroke/TIAandathighischaemicriskaswellaslowbleedingriskreceivingaspirinandclopidogrel,low-doserivaro

50、xaban(2.5mgtwicedailyforapproximatelyoneyear)maybeconsideredafterdiscontinuationofparenteralanticoagulation.IIbBESC2015NSTE-ACSguidelineEffectsofFondaparinuxonMortalityandReinfarctioninPatientsWithAcuteST-SegmentElevationMyocardialInfarction:TheOASIS-6RandomizedTrialJAMA.2006;295(13):1519-1530.doi:1