支架内血栓In-Stent-Thrombosis课件

支架内血栓

In-StentThrombosis

支架内血栓

In-StentThrombosis

Definite/Confirmed（肯定的）AcutecoronarysyndromeAND[Angiographicconfirmationofthrombusorocclusion ORPathologicconfirmationofacutethrombosis]Probable（可能的）Unexplaineddeathwithin30daysTargetvesselMIwithoutangiographicconfirmationofthrombosisorotheridentifiedculpritlesionPossible（不能排除的）Unexplaineddeathafter30daysARC支架内血栓定义Definite/Confirmed（肯定的）ARC支架支架内血栓的预后SimilarmortalityobservedforSESandBMSthrombosisPooledDatafromRAVEL,SIRIUS,C-SIRIUS,E-SIRIUS支架内血栓的预后Similarmortalityobse支架内血栓发生时间ST=stentthrombosis;SAT=subacutestentthrombosis;LST=latestentthrombosis;VLST=verylatestentthrombosis.AdaptedfromBhatt.JInvasiveCardiol.2003;15(supplB):3B.支架内血栓发生时间ST=stentthrombosisStentThrombosis(%)支架内血栓与抗凝、抗血小板治疗ASAundTiclopidineASAundAnticoagulationASAundClopidogrelDESASA=AcetylsalicylicacidDES:Drug-elutingstentBareMetalStentPrasugrel?StentThrombosis(%)支架内血栓与抗凝、抗BMS支架内血栓发生率Days108642003060120600NEarly1.2%(N=71)Late0.4%(N=24)Studypopulation1995-2002-6,058patientsundergoingPCIwithBMSWenaweserPetal.EHJ2005N=1,191N=1,855N=361N=6,058StentThrombosis(%)BMS支架内血栓发生率Days108642003060120DES肯定的ST发生率:

Bern-RotterdamCohortStudy

Daemen,Wenaweseretal.Lancet2007;369:667-780.6%/yearEarlyST91pts(60%)LateST61pts(40%)Incidencedensity:1.3/100patientyearsN=8146DES肯定的ST发生率:

Bern-Rotterdam01234TimesincePCIinyears012345Cumulativeincidence,%Incidencedensity1.0/100ptyears3.3%3.50.53%(95%CI=0.44-0.64)/year192definiteSTcasesDES肯定的ST发生率:

Bern-RotterdamCohortStudy@4YearsWenaweserPetal.JAmCollCardiol2008,52,1134-01234TimesincePCIinyears010.52%(95%CI=0.42-0.62)/yearbetween30daysand5yearsDES肯定的支架内血栓发生率:

Bern-CohortStudy@5YearsWenaweserPetal.ESC20080.52%(95%CI=0.42-0.62)/yearFavours

DESFavoursBMS>180days31-180days0-30daysTimeafterPCI.1.2.5125102050100OddsRatioFavorsDESFavorsBMS.1.2.5125102050100OddsRatioAdjustedResults

withinteractiontermsfortimesincePCIEarlyperiod:0-30daysOR0.59,95%CI.35-1.01Lateperiod:31-180daysOR0.52,95%CI.16–1.75Verylateperiod:>180daysOR9.4,95%CI2.56–34.70Wenaweseretal.ACC2007DESvsBMS

Acohortof9,175patientstreatedwitheitherBMSorDES(SESorPES),allpatientswithangiographicallydocumentedSTwereidentifiedascasesFavoursDESFavoursBMS>180dayEarlyStentThrombosisRR=0.7695%CI=0.30-1.80P=0.55RR=0.8095%CI=0.32-2.03P=0.79Meta-analysisSESvsBMSBavryAetal.AmJCard2005Meta-analysisPESvsBMSStoneGetal.NEJM2007%%EarlyStentThrombosisRR=0.76RVeryLateST>1Year(PerProtocol)P=0.75P=0.02%P=0.30P=0.03%StoneGetal.NEJM2007;356:998-1008KastratiAetal.NEJM2007;356:1030-9Sirolimus-ElutingStentPaclitaxel-ElutingStentVeryLateST>1Year(PeSIRTAX–DefiniteST@4YearsWindeckerSetalESC20082.0%1.8%2.8%2.4%3.7%3.4%1-yearHR1.12[0.46,2.76]P=0.012-yearHR0.86[0.40,1.87]P=0.713-yearHR0.90[0.47,1.73]P=0.754-yearHR1.06[0.57,1.95]P=0.86SES4.2%PES3.9%SIRTAX–DefiniteST@4YearsCumulativeIncidenceofDefiniteST

inLEADERS(BESvs.SES)

Windeckeretal.Lancet,2008,372,1163-Early:1.6%2.0%SES1.9%BESCumulativeIncidenceofDefiniOverallIncidenceofSTwithDESCYPHERTAXUSENDEAVORXIENCEBIOMATRIX0.40.30.70.51.61.40.8TAXUSIITAXUSIVTAXUSVTAXUSVIREALITYSIRTAXISAR-DM10.50.81.9EndeavorIEndeavorIISpiritIIILeaders0.21.120.61.80.800123SIRIUSE-SIRIUSC-SIRIUSREALITYSIRTAXARTSIIISAR-DM%OverallIncidenceofSTwithDHighRiskofSTin

All-ComerPatientPopulationandSTEMIPatients%HighRiskofSTin

All-Comer支架内血栓的病因STENTTHROMBOSISStentDesign/LengthPolymerSurfaceDrugsLesionVesselSizeThrombusInterventionResidualDissectionIncompleteStentAppositionAntithromoboticMedicationPatientGeneticPolymorphismReducedLV-EFAcuteCoronarySyndromeHematologyDisorderDrugsResistanceDrug-drugInteractionDurationofAntiplateletTreatementVesselReactionVesselRemodelingHypersensitivityReactionDelayedHealing支架内血栓的病因STENTTHROMBOSISStentL支架内血栓In-Stent-Thrombosis课件早期支架内血栓的预测因素:

残留夹层/撕裂BareMetalStentsMACE@30daysSchühlenHetal.Circulation1998N=2,894Drug-ElutingStentsMACE@30daysBiondi-ZoccaiGetal.EHJ2006N=2,418%P=0.01P=0.01ResidualDissection:IndependentPredictorofMACE(OR=2.9)早期支架内血栓的预测因素:

残留夹层/撕裂BareMeta早期支架内血栓IVUS预测因素

WiththeUseofSirolimus-ElutingStents

FujiiKetal.JAmCollCardiol2005;45:995-8MinimalStentCSAP<0.001mm2StentExpansionResidualStenosis%P<0.001StentUnderexpansionandResidualReferenceSegmentStenosis:IndependentPredictorsofEarlyStentThrombosis!P<0.001早期支架内血栓IVUS预测因素

WiththeUse

支架内血栓预测因素

药物反应异常

WenaweserPetal.JACC2005;45(11):1748-52

支架内血栓预测因素

药物反应异常

Wenaweser服药后血小板活性与DESST的关系

BuonamiciPetalJACC2007p<0.001p<0.001p<0.001p=ns服药后血小板活性与DESST的关系

BuonamiciPIakovouetalJAMA2005ParketalAmJCard2006AiroldietalCirculation2007KuchulakantietalCirculation2006OR=89.8(29.9-270)HR=19.2(5.6-65.5)HR=13.7(4.0-46.7)OR=4.8(2.0-11.1)Odds/HazardRatio过早停用抗血小板药物是支架内血栓的重要预测因素IakovouetalParketalAiroldi支架内血栓发生时的抗血小板治疗

Bern-RotterdamCohortStudy@5Years

WenaweserPetal.ESC2008支架内血栓发生时的抗血小板治疗

Bern-RotterdTritonTIMI38–Prasugrelvs.ClopidogrelinACSPatientsWithStentsWiviottSDetal.Lancet2008;371:1353-63OverallStentThrombosisEarlyStentThrombosisLateStentThrombosisTritonTIMI38–Prasugrelvs.ParketalAmJCard2006AiroldietalCirculation2007IakovouetalJAMA2005MachecourtetalJACC2007OR=1.03(1.00-1.05)OR=1.01(1.00-1.03)OR=2.75(1.55-4.88)OddsRatio支架内血栓的预测因素-支架长度OR=1.02(1.00-1.04)OR=1.08(1.06-1.1)DelaTorreetalJACC2008ParketalAiroldietalIakovouRoyetalJIntervCard2007KuchulakantietalCirculation2006OR=4.4(2.0-10.0)OddsRatio支架内血栓的预测因素-分叉病变OR=2.4(1.1-5.6)IakovouetalJAMA2005OR=6.4(2.9-14.1)OngetalJACC2005*OR=12.9(4.7-35.8)*insettingofAMIJoneretalJACC2006RoyetalKuchulakantietalOR=ParketalAmJCard2006DaemenetalLancet2007UrbanetalCirculation2006OR=12.4(1.7-89.7)OR=2.3(1.3-4.0)OR=1.8(1.1-2.7)Odds/HazardRatio支架内血栓的预测因素-ACS

DelaTorreetalJACC2008HR=2.6(1.3-4.9)ParketalDaemenetalUrbanetImpactofThrombusBurdenonRiskofST

WithDESinPatientsWithSTEMI

SianosGetal.JAmCollCardiol2007;50:573-83Variable HazardRatio 95%CIAge 0.6 0.4-0.8IndexST 6.2 2.1-18.9Bifurcation 4.1 1.6-10.0Thrombectomy 0.1 0.01-0.8Largethrombus 8.7 3.4-22.5IndependentPredictorsofSTImpactofThrombusBurdenonRKuchulakantiCirc2006UrbanCirc2006IakovouJAMA2005DaemenLancet2007MachecourtJACC2007OR=2.0(0.8-4.9)OR=2.8(1.7-4.3)HR=3.7(1.7-7.9)HR=2.0(1.1-3.8)OR=2.7(1.4-5.2)Odds/HazardRatio支架内血栓的预测因素-糖尿病IijimaAmJCard2007HR=2.2(1.1-4.3)HR=1.75(1.0-3.0)DelaTorreJACC2008KuchulakantiUrbanIakovouDaem晚期支架内血栓的可能原因ChronicinflammatoryreactiontothepolymerordrugHypersensitivitytothepolymerordrugFailureofstentstocompletelyreendothelializecompletelyLateincompletestentappositionDiseaseprogression晚期支架内血栓的可能原因Chronicinflammato多聚物高敏多聚物高敏获得性晚期支架贴壁不良Baseline8mofollow-upSIRIUSTrial:7/80(8.7%)patients,no12-monthMACEAkoJ.etal.JACC2005;46:1002-5获得性晚期支架贴壁不良BaselineCooketal.Circulation2007Kotanietal.JACC2006Joneretal.JACC2006Tognietal.JACC2005AbnormalVasomotionDelayedHealingDelayedEndothelializationVesselRemodeling

DES后病生理机制EndothelializationCooketal.Circulation2007Ko小结DES支架内血栓发生率：Early:0.5%-1.6%Late/Verylate:0.3%-0.6%预测因素Residualdissection,stentunderexpansionDiabetes,ACS,bifurcationstenting,stentlength,thrombusburden,lateaquiredstentmalapposition,ineffectiveplateletinhibition小结DES支架内血栓发生率：

支架内血栓的预防高危病人的辨认避免过度支架长支架,分叉支架,支架重叠支架植入的理想结果无残留撕裂/夹层支架膨胀良好增加抗血小板治疗的有效性高危病人评估抗血小板药物的反应性再狭窄低危病人中使用BMS支架内血栓的预防高危病人的辨认专家共识FDADESPanelMeetingThereisanincreasein“verylate”(>1yr)stentthrombosisassociatedwithcurrentDES~2-4per1000ptsperyear(?continoushazard,

?patientandlesionpredictors)Datafrommultiplesourcesindicatethat

DESareassociatedwithdelayedhealing

responsesandincreasedinflammationThecausesoflateDESthrombosisaremulti-

factorial;device,procedural,andpatient

factors(oftenmultiple=perfectstorm)专家共识FDADESPanelMeetingThere专家共识FDADESPanelMeetingTheremaybealinkbetweenpost-DESreducedneo-intimalhyperplasia(lateloss)anddelayedlatehealingresponseswhichcontributestolatestentthrombosis

DESstentthrombosisishighlydefinition

dependent;needforrevisedstandardized

definitionsandadjudicationmethods(ARC)

tofacilitateinter-studycomparisons专家共识FDADESPanelMeeting专家共识“Off-labelDESuse–increasedincidenceoflateDESthrombosisanddeath/MIcw“on-label”,but

inadequatecontrols;resultsinconsistent!

FewRCTs(underpowered);FDAsanctionedregistries=insufficientsamplesizeandFU,representsmajordatagapandsourceofconcernLargepopulationstudies(SCAAR)fraughtwithmethodologicflaws(e.g.riskadjustmentissues)

专家共识“Off-labelDESuse–incre专家共识Durationofdualanti-platelettherapyshouldextendbeyondthepresentproductlabelsOneyearisreasonablecompromise(esp.for

“off-label”DESuse)Mustbalanceagainsttheincreasedriskof

bleedingwithdualanti-platelettherapyAdditionalstudiesimmediatelyrequiredto

betterclarifyoptimalanti-platelettherapy专家共识Durationofdualanti-plat专家共识AssesspatientandlesioncharacteristicstoestablishrestenosisriskprofileDeterminerelativevalueofDESvs.BMSin

everypatient(nomore“unrestricted”use)Considerbothon-labelandoff-label

situations(ironically,off-labelusescenariosmaybemorecompelling)Increasedrestenosisrisk=favorDESIncreasedsafetyconcerns=favorNoDES

专家共识Assesspatientandlesion专家共识Assesspatientfactorswhichmayprecludelong-term(atleastoneyear)dualAPtherapyPlannedorpossibleintercurrentsurgeryBleedingHxortendenciesOtherconcomitantmedications(e.g.coumadin)Socio-economicfactorswhichmayaffectPlavixcompliance

专家共识Assesspatientfactorswhi专家共识ConsideralternativestoDES,ifris