急性心肌梗塞的溶栓治疗.ppt

CombinationLyticTherapyinAcuteMyocardialInfarction,C.MichaelGibson,M.D.,PathophysiologyofCombinationTherapyinAMI,*Gibsonetal.JAmCollCardiol.2019;25:582-589.Gibsonetal.Circulation.2019;103:2550-2554.,CombinationTherapy,Thrombus,%StenosisMinimumDiameter,EpicardialFlow,MyocardialBlushSTResolution,MyocardialFlow,FacilitatesPCI,ReducesReinfarction*,RecentClinicalTrials,UnfractionatedheparinEnoxaparinUnfractionatedheparinEnoxaparin,AbciximabAbciximabNoneNone,ENTIRE,ACC/AHAheparindoseLow-doseheparinEnoxaparin,NoneAbciximabNone,ASSENT-3,Standard-doseheparinLow-doseheparin,NoneAbciximab,50%TNK-tPA50%TNK-tPA100%TNK-tPA100%TNK-tPA,100%TNK-tPA50%TNK-tPA100%TNK-tPA,100%r-PA50%r-PA,GUSTO-V,Anticoagulant,GPIIb/IIIaReceptorInhibitor,Lytic,Trial,ClinicalTrials:Ongoing,Low-doseheparinLow-doseheparinLow-doseheparin,EptifibatideEptifibatideEptifibatide,50%TNK-tPA75%TNK-tPA100%TNK-tPA,INTEGRITI,Low-doseheparinLow-doseheparinLow-doseheparin,TirofibanTirofibanTirofiban,50%TNK-tPA75%TNK-tPA100%TNK-tPA,FASTER,Anticoagulant,GPIIb/IIIaReceptorInhibitor,Lytic,Trial,54%,32%,GUSTO-I:A20%IncreaseinTIMIGrade3FlowisNeededtoYielda1%MortalityReduction,TheGUSTOAngiographicInvestigators.NEnglJMed.1993;329:1615-1622.,0,30,50,60,40,20,%TIMIGrade3Flow,t-PA,SK,10,t-PA,5,7.4%,6.3%,SK,8,7,6,TIMIGrade3FlowPooledDataFromDoseConfirmationPhasesofRecentTrials,0,40,80,100,60,20,%PatientsWithTIMIGrade3Flow,GUSTO-I90min,T14t-PA90min,T14r-PA90min,SPEED60-90min,INTRO-AMI60min,Pooled60-90min,54,73,70,47,40,56,78,73,54,56,64,292,63,87,98,81,329,58,88,100,75,321,Lyticalone,Combination,SPEED:ResultsofDose-ConfirmationPhase,Therewasa7.4%improvementintherateofTIMIGrade3flowIfa20%improvementisrequiredtoimprovemortalityby1%,thena7.4%improvementwouldbepredictedtoimprovemortalityby0.3%,TheSPEEDStudyGroup.Circulation.2000;101:2788-2794.,0,40,80,100,r-PA10+10U,r-PA5+5U+Abx,60,20,Patency(%),TIMI-2,TIMI-3,n=109,n=115,21.6,54.9,47.5,28.7,GUSTO-V:StudyDesign,TheGUSTO-VInvestigators.Lancet.2019;357:1905-1914.,ST,lyticeligible,6h(n=16,588),ASA,NoAbciximab,2x10Ubolus(30)Full-doser-PA,Abciximab,Low-doseHeparin:60U/kgbolusfollowedby7U/kg/hinfusion,1endpoint:mortalityat30days2endpoint:clinicalandsafetyeventsat30days,2x5Ubolus(30)Half-doser-PA,StandardHeparin:5000Ubolusfollowedby800U/h(80kg)or1000U/h(80kg)infusion,PrimaryEndPoint:30-DayMortality,TheGUSTO-VInvestigators.Lancet.2019;357:1905-1914.,0,%Mortality,Days,0,5,10,15,20,25,30,P=.43forsuperiority,Non-InferiorityRR0.95(95%CI,0.84-1.08),Std.Reteplase(n=8260),Abx+DoseReteplase(n=8328),4,6,2,5.9%,5.6%,GUSTO-V:NoninferiorityAnalysis,AdaptedwithpermissionfromtheGUSTO-VInvestigators.Lancet.2019;357:1905-1914.,Non-InferiorityRR0.95(95%CI,0.84-1.08),1.11,ORand95%CI,0.0,2.0,1.0,Abciximab+Half-doser-PAsuperior,Full-doser-PAsuperior,UpperBoundaryof95%CIforNoninferiority,AComparisonoftheOutcomesWithr-PAMonotherapyinGUSTO-IIIvsGUSTO-VTrials,TheGUSTO-IIIInvestigators.NEnglJMed.2019;337:1118-1123.TheGUSTO-VInvestigators.Lancet.2019;357:1905-1914.,0,3,7,8,5,1,2,6,4,GUSTOIII,GUSTOV,10,138,8,260,Death,P75yrs,0.4,1.2,0.5,1.1,1.5,0.4,2.1,r-PA(n=8260),r-PA+Abx(n=8328),0.3,P=.66,P=.53,P=.27*,P=.069*,12/1088,24/1149,28/7179,37/7172,25/2030,31/2135,21/6193,24/6230,*,*,*,*,GUSTO-V:PCIWithin6Hours(Urgent)andThroughDay7,*P.0001.TheGUSTO-VInvestigators.Lancet.2019;357:1905-1914.,5.6,25.4,27.9,8.6,0,15,25,30,20,10,PCI(%),Urgent,ThroughDay7,5,r-PA,r-PA+Abx,2.8,9.0,5.4,GUSTO-V:EventRatesinThoseRequiringUrgentPCI,HeartwireNews.September2,2019.GUSTO-V:Combinationhalf-dosefibrinolyticplusIIb/IIIablocker.AnAlternativeapproachtoMI?,6.7,4.8,9.6,0,4,10,12,8,MyocardialInfarction(%),r-PA,r-PA+Abx,n=1173,Death,RepeatMI,DeathPlusRepeatMI,2,6,GUSTO-V:Conclusions,Comparedwithr-PAmonotherapy,combinationtherapywithr-PAandabciximabresultedinAmortalityratethatwasnotinferiortor-PAmonotherapyFewernonfatalreinfarctions(primarilyareducedincidenceofrecurrentSTelevation)AlowerrateofurgentrevascularizationMorenoncerebralbleedingcomplications,transfusions,andthrombocytopeniaAhigherrateofICHinelderlypatientsovertheageof75years,ASSENT-3:RationaleforUseofEnoxaparin,TNK-tPAplusenoxaparinFavorableeffectsofLMWHsinrecentsmall-scalethrombolysistrialsHigherlatepatency:HART-2ASSENT-PlusAMI-SKLessreocclusion:HART-2Fewerreinfarctions:ASSENT-PlusAMI-SKWilson,etal.ASSENT-3isthefirstlarge-scaletrialtotestLMWH,ASSENT-3:StudyDesign,ST-SegmentElevationAMI(n=6095patients),150to325mgASA(daily),Randomized,Full-doseTNK-tPAPlusEnoxaparin,Half-doseTNK-tPAPlusAbciximabPlusLow-doseHeparin,Full-doseTNK-tPAPlusWeight-adjustedUFH,TheASSENT-3Investigators.Lancet.2019;358:605-613.,ASSENT-3:PrimaryEndPoints,PrimaryEfficacyEndPoint:Compositeof30-daymortalityorin-hospitalreinfarctionorin-hospitalrefractoryischemia.PrimaryEfficacyPlusSafetyEndPoint:Compositeof30-daymortalityorin-hospitalreinfarctionorin-hospitalrefractoryischemiaplusin-hospitalintracranialhaemorrhageorin-hospitalmajorbleedingotherthanintracranial.,ASSENT-3:30-DayMortality,RecurrentMI,RefractoryIschemia,0,5,10,15,20,%Riskof30-DayD/MI/RefIsch,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,*P-valuesaretheBonferroniP-valuesaftercorrectingformultiplecomparisons.TheuncorrectedP-valueswereP=.0002fortheenoxvsUFHcomparison,andP75YearsofAge,*Therewasastatisticallysignificantinteractionbetweentreatmentwithabciximabandagesuchthatpatientsovertheageof75hadpooreroutcomeswithabciximab(P=.001).,%Riskof30-DayEfficacyandSafetyEndPoint,0,15,25,35,45,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,25.5,36.9,P=.001*,5,20,30,40,10,ASSENT-3:PrimaryEfficacyandSafetyEndPointofDeath,ReinfarctionorRefractoryIschemia,ICHorMajorBleedinginPatientswithDiabetes,*Therewasastatisticallysignificantinteractionbetweentreatmentwithabciximabanddiabetes,suchthatdiabeticshadpooreroutcomeswithabciximabtherapy(P=.0007).,%Riskof30-DayEfficacyandSafetyEndPoint,0,15,25,30,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,13.9,22.3,P=.007*,5,20,10,ASSENT-3:30-DayMortality,0,4,8,10,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,5.4,6.6,3-wayP=.25,6,2,%Riskof30-DayMortality,ASSENT-3:30-DayDeathorMI,%Riskof30-DayDeathorMI,0,4,8,10,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,6.8,7.3,3-wayP=.0198,6,2,ASSENT-3:In-HospitalRecurrentMI,%RiskofIn-HospitalRecurrentMI,0,2,4,5,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,2.7,2.2,3-wayP=.0009,3,1,ASSENT-3:In-HospitalRefractoryIschemia,%Riskof30-DayRefractoryIschemia,0,4,8,10,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,4.6,3.2,3-wayP.0001,6,2,ASSENT-3:IncidenceofIn-HospitalThrombocytopeniaandNoncerebralBleedingComplications,*While3-wayP-valueissignificant,EnoxvsUFHcomparisonP=NS,EnoxAbxUFHP-Value(n=2040)(n=2019)(n=2038)3-way,Anythrombocytopenia.0001Thrombocytopenia.000120,000cells/L20,000to50,000cells/L50,000to100,000cells/L0.92.01.0BleedingepisodesTotal25.6*39.721.1.0001Major3.0*005Minor22.6*35.418.8.0001Bloodtransfusion3.4*032,ASSENT-3:In-HospitalStrokeRates,*Includinghemorrhagicconversion,PatientsUndergoingPCI:Mortality,ASSENT-3:In-HospitalPCI,GUSTO-V:UrgentPCI,0,5,7,8,6,3,Mortality(%),4,2,1,2.5,3.7,2.7,5.4,6.7,TNK-tPA+Enox,TNK-tPA+Abx,TNK-tPA+UFH,r-PA+UFH,r-PA+Abx,HowDoesActualWeightComparetoEstimatedWeight?,ReprintedwithpermissionfromCannonCP,etal.JAmCollCardiol.2019;37:323A.,CorrelationBetweenEstimatedandActualPatientWeightinTIMI10B,40.5,36.4,188.5,ActualPatientWeight(kg),EstimatedPatientWeight(kg),R2=0.93,P.0001,181,Weight-BasedDosingofThrombolysis:HowWellDoWeEstimateWeight?HowOftenWouldThisTranslateIntoErrorsWithAdministrationofThrombolyticDrugsandAdverseOutcomes?,Errorsinestimatingweightareuncommon,especiallythosethatwouldleadtoadosechange(1.3%or49/3730forTNK-tPAand4.5%or13/290fort-PA).Noadverseoutcomeswereseenamongpatientswhoreceivedanincorrectdose,suggestingabroadsafetyprofileforthenewsingle-bolusagentTNK-tPA.,CannonCP,etal.JAmCollCardiol.2019;37:323A.,ASSENT-3:StudyGroupConclusionsRegardingTNK-tPA+AbciximabTherapy,“Theresultsobtainedwithhalf-dosetenecteplaseplusabciximabareverysimilartothosewithhalf-dosereteplaseandabciximabseeninGUSTO-V.”“Inbothtrials,thesebenefitsareobtainedatthecostofahigherrateofmajorbleedingcomplicationsandbloodtransfusions.”“Nobenefitandperhapsevenharmwasobservedinpatientsabove75yearsandindiabetics.”“Takentogethertheysuggestthatcautionshouldbeexercisedregardingtheuseofconjunctivetherapywithabciximabinelderlypatientswithanacutemyocardialinfarctiontreatedwithafibrinolyticagent.”,TheASSENT-3Investigators.Lancet.2019;358:605-613.,ASSENT-3:StudyGroupConclusionsRegardingEnoxaparin,“Inviewofthepresentdataandtheeaseofadministration,enoxaparinmightbeconsideredanattractivealternativeanticoagulanttreatmentwhengivenincombinationwithtenecteplase.”,TheASSENT-3Investigators.Lancet.2019;358:605-613.,ENTIRETIMI-23:StudyDesign,STMI6h(n=461),UFH60U/kgbolus12U/kg/hinfusion36h,ENOXvaryingdoses+/-IVbolusIndexHosp(8d),ASA,ENOXvaryingdoses+/-IVbolusIndexHosp(8d),CombinationReperfusion:Half-doseTNK-tPA+Abx(0.27mg/kg),Stan