溶栓和急诊PCI在急性心梗治疗中的作用课件

S.ChiuWongMD,FACC

AssociateProfessorofMedicine

WeillMedicalCollegeofCornellUniversity

Director,CardiacCatheterizationLaboratories

TheNewYorkPresbyterianHospital-CornellCampusTheACCSymposiumattheGreatWallMeeting,BeijingChinaOctober17,2004ThrombolysisorPrimaryPCIintheTreatmentofAcuteMIPatho-anatomyofAMIFibrinolysisforAMIFibrinolysisVs.PrimaryPCIAdjunctPharmacologyandStrategiesCurrentRecommendationsinTreatmentofAMIThrombolysisorPCIinAMI

SummaryPatho-anatomyofAMIFibrinolysisforAMIFibrinolysisVs.PrimaryPCIAdjunctPharmacologyandStrategiesCurrentRecommendationsinTreatmentofAMIThrombolysisorPCIinAMICirculation,VolumeXLV,January1972.230CoronaryArteriesinFatalAcuteMyocardialInfarctionByWILLIAMC.ROBERTS,M.D.SUMMARYThecoronaryarteriesarediffuselyinvolvedbyatheroscleroticplaquesinfatalacutemyocardialinfarction(AMI).Thedegreeofluminalnarrowingmayvarybutplaquesarepresentinpracticallyeverymillimeterofextramuralcoronaryartery.Usuallythelumensofatleasttwoofthethreemajorcoronaryarteriesarenarrowed>75%byoldplaquesinpatientswhodiesuddenly(<6hours)fromcardiacdiseasewithorwithoutmyocardialnecrosis.Coronarythrombioccurinabout10%ofpatientswhodiesuddenlyorinwhomnecrosisislimitedtotheleftventricularsubendocardium,andinabout50%ofpatientswithtransmuralmyocardialnecrosis.Coronarythrombiusuallyindicatethepresenceofshockorcongestiveheartfailureorbothduringdiedevelopmentofmyocardialnecrosis.TheinfrequencyofcoronarythrombiinpatientsdyingsuddenlyofcardiacdiseaseandinthosewithtransmuralnecrosiswhoneverhaveshockorcongestiveheartfailuresuggeststhatthethrombimaybeconsequencesratherthancausesofAMI.

ThrombolysisorPCIinAMI

Patho-AnatomyofAMIThrombolysisorPCIinAMI

Patho-AnatomyofAMIThrombolysisorPCIinAMI

Patho-AnatomyofAMIThrombolysisorPCIinAMI

PathophysiologyofST-ElevationMIResultsfromstabilizationofa

plateletaggregateatsiteof

plaquerupturebyfibrinmeshplateletRBCfibrinmeshGPIIb-IIIaMIgenerallycausedbya

completelyocclusive

thrombusinacoronaryarteryIncidenceandPatho-anatomyofAMIFibrinolysisforAMIFibrinolysisVs.PrimaryPCIAdjunctPharmacologyandStrategiesCurrentRecommendationsinTreatmentofAMIThrombolysisorPCIinAMIThrombolysisorPCIinAMI

ISIS-2(Secondinternationalstudyofinfarctsurvival)Randomizedtrialcomparing1MUofivstreptokinaseover1hr,oralaspirin,both,orneitheramong17,187ptswithsuspectedAMIupto24hrsafteronsetofsymptom.Significantreductionofmortalityat35dayswasdemonstratedforaspirinorstreptokinase,andanadditivebeneficialeffectwiththe2combinedagentswasnoted.ISIS-2CollaborativeGroup.Lancet1988;332:349–360ThrombolysisorPCIinAMI

ThrombolyticAgentsforAMIComprehensiveoverviewofthrombolytictherapyonAMIonearly(5-week)mortalityfromrandomizedtrialsofmorethan1000ptsbythefibrinolyticcollaborativegroup……FCGThelancet1994;343:311-22ThrombolyticsarebeneficialacrossabroadspectrumofAMIptswithSTEorBBBperhapswiththeexceptioninptswhowere>75yrsandtreated>12hrsfromsxonsetwere.Theearliertreatmentinitiation,thegreaterthebenefitandthusre-affirmtheconceptof“timeismuscle.”NoteverypatientiseligibleforthrombolytictreatmentCerebral/vascularbleedPercentAMIptswithTIMI3flowfollowingthrombolysisislessthanidealThrombolysisorPCIinAMI

LimitationsofThrombolysisinAMIPatientsThrombolysisorPCIinAMI

ContraindicationsforfibrinolyticsinAMIContraindicationsPrevioushemorrhagicstrokeatanytime;otherstrokesorcerebrovasculareventswithin1yrKnownintracranialneoplasmActiveinternalbleeding(doesnotincludemenses)SuspectedaorticdissectionAdaptedfromRyanTJ,etal.ACC/AHAguidelinesforthemanagementofpatientswithAMI.JAmCollCardiol1996;28:1328–1428RelativecontraindicationsSevereuncontrolledhypertensiononpresentation(bloodpressure>180/110mmHg)orchronichistoryofseverehypertensionHistoryofpriorcerebrovascularaccidentorknownintracerebralpathologynotcoveredincontraindicationsCurrentuseofanticoagulantsintherapeuticdoses(internationalnormalizedratio2–3);knownbleedingdiathesisRecenttrauma(within2–4wk),includingheadtraumaortraumaticorprolonged(>10min)cardiopulmonaryresuscitationormajorsurgeryNoncompressiblevascularpuncturesRecent(within2–4wk)internalbleedingForstreptokinase/anistreplase:priorexposure(especiallywithin5d–2yr)orpriorallergicreactionPregnancyandActivepepticulcerAdaptedfromRyanTJ,etal.ACC/AHAguidelinesforthemanagementofpatientswithAMI.JAmCollCardiol1996;28:1328–1428ThrombolysisorPCIinAMI

ContraindicationsforfibrinolyticsinAMIPreviouslarge-scalerandomizedthrombolyticstudieswouldsuggestthatonly15-20%ofAcuteMI(AMI)patientsareconsideredeligibleforreperfusiontherapybyconventionalcriteriaMorerecentobservationalstudies*withbroaderinclusioncriteriawouldestimatethatapproximately45to50%ofAMIptswereeligible(ie.<12hrssymptomonset,chestpainwith≥2mmST↑inany2contiguousECGleadsornewLBBB)and32-45%ofptsactuallyreceivedthrombolyticagents.ThrombolysisorPCIinAMI

EligibilityforThrombolysisinAMIPatientsKarlsonBWetalCirc1990;82:1140-6,*FrenchJKetalBMJ1996;312:1637-41*ReikvmetalIntJCardiol1997;61:79-83NoteverypatientiseligibleforthrombolytictreatmentCerebral/vascularbleedandre-infarctionPercentAMIptswithTIMI3flowfollowingthrombolysisislessthanidealThrombolysisorPCIinAMI

LimitationsofThrombolysisinAMIPatientsReteplaseN=8260Reteplase+ReoproN=8326OR(95%CI)Pvalue30-daymortality5.9%5.6%0.95(0.84-1.08)0.43Re-MIupto7days6(0.72-0.93)<0.0001Stroke(any)0.9%1.0%1.1(0.8-1.51)0.55Intra-cranialbleed>75yrs1(0.95-3.84)0.069Sever/Mod.Bleed3(1.7-2.42)<0.0001ThrombolysisorPCIinAMI

GUSTOV:PrimaryandSecondaryEndpoints16,588ptswithin6hrsofSTEMIrandomizedtostandarddoseofreteplase(n=8260)or½-dosereteplaseandfull-doseReopro(n=8328).TheGUSTOVInvestigators.Lancet2001;357:1905-14NoteverypatientiseligibleforthrombolytictreatmentCerebral/vascularbleedPercentAMIptswithTIMI3flowfollowingthrombolysisislessthanideal

ThrombolysisorPCIinAMI

LimitationsofThrombolysisinAMIPatientsThe90MinuteWall:60%RatesofTIMIGrade3Flow%TIMI3FlowIncidenceandPatho-anatomyofAMIFibrinolysisforAMIFibrinolysisVs.PrimaryPCIAdjunctPharmacologyandStrategiesCurrentRecommendationsinTreatmentofAMIThrombolysisorPCIinAMIGrines,C.L.etal.NEnglJMed1993;328:673-679ThrombolysisorPCIinAMI

PAMI:In-HospitalReinfarctionandDeath395Ptswereenrolledin12siteswithAMIwithin12hrsofsymptomonsetandrandomizedtoimmediatePTCA(n=195)vs.tPA(n=200)By6months,reMIordeathhadoccurredin15.8%ofptstreatedwithtPAand8.5%treatedwithPTCA(p=0.02).ThrombolysisorPCIinAMI

Short(4-6wks)-termclinicalOutcomesPost1°PTCAVs.ThrombolysisKeeleyetal,Lancet2003;361:13-20Summaryof23trialstotaling7,739pts(PTCA=3,872andThrombolysis=3,867pts)27%65%54%47%ThrombolysisorPCIinAMI

AdvantagesandDisadvantagesof1°PTCAVs.ThrombolysisAdvantagesDisadvantagesSuperiorvesselpatencyandTIMI3flowLackofgeneralizedavailabilityEarlydefinitionofcoronaryanatomyallowsriskstratificationDelayinmobilizingcathlabReducedratesofrecurrentischemia,re-MI,death,andstrokeSkilledinterventionalcardiologysrequiredImprovedsurvivalinhighriskpatientsNolargesinglemortalitytrialdataavailableReducedintracranialbleedShorterlengthofhospitalstayAllowsreperfusionwhenthrombolyticsarecontra-indicatedIncidenceandPatho-anatomyofAMIFibrinolysisforAMIFibrinolysisVs.PrimaryPCIAdjunctPharmacologyandStrategiesCurrentRecommendationsinTreatmentofAMIThrombolysisorPCIinAMIThrombolysisorPCIinAMI

TheADMIRALTrialMulti-center300ptsrandomized,double-blindplacebocontrolledstudytodemonstratethesuperiorityofabciximaboverplaceboinprimaryPTCAwithstentinginacutemyocardialinfarctionMontalescotGetalNEJM2001;344:1895-1903ThrombolysisorPCIinAMI

ADMIRAL:FrequencyofTIMIIIIFLOWP=0.01P=0.04P=0.33P=0.04MontalescotGetalNEJM2001;344:1895-1903ThrombolysisorPCIinAMI

ADMIRAL:CompositeEndpoint@6monthP=0.13MontalescotGetalNEJM2001;344:1895-1903P=0.32P=0.049P=0.02Reoproimprovescoronarypatencybeforestenting,andclinicaloutcomeat30daysand6monthsN=149N=151ThrombolysisorPCIinAMI

CAPTIM:StudyDesignPrimaryCompositeEndpoint-30-dayDeath,Reinfarction,DisablingStrokeBonnefoyE,etal.Lancet2002;360:825-9ComparisonofAngioplastyandPrehospital

ThrombolysisinAcuteMyocardialInfarctionThrombolysisorPCIinAMI

CAPTIM:StudyDesignP=0.61P=0.13P=0.12P=0.29BonnefoyE,etal.Lancet2002;360:825-9PrimaryPTCAwasnotbetterthanpre-hospitalthrombolysiswithtransferforpossiblerescuePTCAinptswith<6hronsetofAMIHigh-riskSTelevationMIpatients(>4mmelevation),Sx<12hrs5PCIcenters(n=443)and22referringhospitals(n=1,129),transferin<3hrsLytictherapyFront-loadedtPA100mg(n=782)Death/Re-MI/Strokeat30DaysThrombolysisorPCIinAMI

DANAMI-2:StudyDesignPrimaryPCIwithtransfer(n=567)PrimaryPCIwithouttransfer(n=223)StoppedearlybysafetyandefficacycommitteeAndersonHRetalNEJM2003;349:733-42Death/MI/Stroke(%)LyticPrimaryPCIP=0.0003P=0.002CombinedTransferSitesP=0.048Non-TransferSitesThrombolysisorPCIinAMI

DANAMI-2:PrimaryResultsRRR45%LyticPrimaryPCILyticPrimaryPCIRRR40%RRR45%AndersonHRetalNEJM2003;349:733-42LyticPrimaryPCIP=0.35DeathThrombolysisorPCIinAMI

DANAMI-2:ResultsLyticPrimaryPCIP=0.15StrokeLyticPrimaryPCIP<0.0001RecurrentMIAndersonHRetalNEJM2003;349:733-4296%OFPTSWERETRANSFERREDFROMREFERRALHOSP.TOINVASIVECETNERWITHIN2HRSThrombolysisorPCIinAMI

Prague2:Longdistanttransfervs.ThrombolysisinAMIMulticenterCzechstudyinvolving850ptswithSTelevationMIwithin12hrsofsymptomonset.Primaryendpointwas30-daymoratlity,andcompositesecondaryendpointswere:death,re-MI,strokeat30days.WidimskyPetalEurHeartJ2003;24:94-104ThrombolysisorPCIinAMI

Prague2:Longdistanttransfervs.ThrombolysisinAMIP=0.12P=NSP<0.02P<0.003Forptswithin3hrsofsymptoms,thrombolysisortransferforPCIiscomparablestrategy.However,forptspresent>3hrsofsymptomonset,PCIresultsinbetterclinicaloutcomedespitelongdistancetransfer.WidimskyPetalEurHeartJ2003;24:94-104ThrombolysisorPCIinAMI

C-port:KeyFindingsP=0.72P=0.04P=0.28P=0.03AversanoTetalJAMA2002;287:1943-51TimetoPerfusionVolumeofHospitalandexperienceofOperatorThrombolysisorPCIinAMI

WhatElseisImportantinAMITreatmentStrategy?AdditionalimportantparameterstomaximizequalityofcareinthetreatmentofAMIpatientsN=27,080,P<0.00001ThrombolysisorPCIinAMINRMI-2:PrimaryPCIDoor-to-Balloontimevs.MortalityDoor-to-BalloonTime(minutes)ThrombolysisorPCIinAMI

MortalityrateswithprimaryPCIasafunctionofPCI-related

timedelayP=0.0060 20 40 60 80 100PCI-RelatedTimeDelay(door-to-balloon-doortoneedle)AbsoluteRiskDifferenceinDeath(%) -5 0 5 10 15Circle

sizes= samplesizeoftheindividualstudySolidline = weightedmeta-regression

NallamothuBK,BatesER.AmJCardiol.2003;92:824-662minBenefit

FavorsPCIHarm

FavorsLysisForEvery10mindelaytoPCI:1%reductioninmortalitydifferencetowardslyticsMeta-analysisof23studieswith7419ptsTimetoPerfusionVolumeofHospitalandexperienceofOperatorThrombolysisorPCIinAMI

WhatElseisImportantinAMITreatmentStrategy?AdditionalimportantparameterstomaximizequalityofcareinthetreatmentofAMIpatientsThrombolysisorPCIinAMINRMI-2:HospitalVolumeofPrimaryPCIvs.Mortality

N=4,740 14,078 8,262P=0.033P=0.00010.860.67IncidenceandPatho-anatomyofAMIFibrinolysisforAMIFibrinolysisVs.PrimaryPCIAdjunctPharmacologyandStrategiesCurrentRecommendationsinTreatmentofAMIThrombolysisorPCIinAMIThrombolysisorPCIinAMI

ImportanceofEarlyReperfusionTherapyinSTEMIOutcomesDependentUpon:Timetotreatment-TIMEISSTILLMUSCLE

EarlyandfullrestorationincoronarybloodflowSustainedrestorationofflowThrombolysisorPCIinAMIPharmacologicalReperfusion

AvailableResourcesClassI1.STEMIpatientspresentingtoafacilitywithoutthecapabilityforexpert,promptinterventionwithprimaryPCIwithin90minutesoffirstmedicalcontactshouldundergofibrinolysisunlesscontraindicated.(LevelofEvidence:A)Antmanetal.JACC2004;44:682.ThrombolysisorPCIinAMI

FibrinolyticTherapyClassI

Intheabsenceofcontraindication,fibrinolytictherapy shouldbeadministeredtoSTEMIpatientswith symptomonsetwithintheprior12hours&STelevation

2.Intheabsenceofcontraindications,fibrinolytictherapy shouldbeadministeredtoSTEMIpatientswith symptomonsetwithintheprior12hoursand neworpresumablynewLBBB.(LevelofEvidence:A)Antmanetal.JACC2004;44:682-3.ThrombolysisorPCIinAMI

PrimaryPercutaneousCoronaryInterventionClassI

1.Generalconsiderations:Theprocedureshouldbesupportedbyexperiencedpersonnelinanappropriatelaboratoryenvironment(performsmorethan200PCIproceduresperyear,ofwhichatleast36areprimaryPCIforSTEMI,andhascardiacsurgerycapability).(LevelofEvidence:A)

Antmanetal.JACC

2004;44:682.ThrombolysisorPCIinAMI

PrimaryPercutaneousCoronaryInterventionClassI

2.SpecificConsiderations:a.PrimaryPCIshouldbeperformedasquicklyaspossible,withagoalofamedicalcontact–to-balloonordoor-to-balloontimeofwithin90minutes.(LevelofEvidence:B)b.Ifthesymptomdurationiswithin3hoursandtheexpecteddoor-to-balloontimeminustheexpecteddoor-to-needletimeis:i)within1hour,primaryPCIisgenerallypreferred.(LevelofEvidence:B)ii)greaterthan1hour,fibrinolytictherapy(fibrin-specificagents)isgenerallypreferred.(LevelofEvidence:B)c.Ifsymptomdurationisgreaterthan3hours,primaryPCIisgenerallypreferredandshouldbeperformedwithamedicalcontact–to-balloonordoor-to-balloontimeasbriefaspossible,withagoalofwithin90minutes.(LevelofEvidence:B)Antmanetal.JACC

2004;44:684PrimaryPercutaneousCoronaryIntervention

FacilitatedPCIClassIIbFacilitatedPCImightbeperformedasareperfusionstrategyinhigher-riskpatientswhenPCIisnotimmediatelyavailableandble