支架內血栓

In-StentThrombosis

支架內血栓

In-StentThrombosis

Definite/Confirmed（肯定的）AcutecoronarysyndromeAND[Angiographicconfirmationofthrombusorocclusion ORPathologicconfirmationofacutethrombosis]Probable（可能的）Unexplaineddeathwithin30daysTargetvesselMIwithoutangiographicconfirmationofthrombosisorotheridentifiedculpritlesionPossible（不能排除的）Unexplaineddeathafter30daysARC支架內血栓定義Definite/Confirmed（肯定的）ARC支架支架內血栓的預后SimilarmortalityobservedforSESandBMSthrombosisPooledDatafromRAVEL,SIRIUS,C-SIRIUS,E-SIRIUS支架內血栓的預后Similarmortalityobse支架內血栓發生時間ST=stentthrombosis;SAT=subacutestentthrombosis;LST=latestentthrombosis;VLST=verylatestentthrombosis.AdaptedfromBhatt.JInvasiveCardiol.2003;15(supplB):3B.支架內血栓發生時間ST=stentthrombosisStentThrombosis(%)支架內血栓與抗凝、抗血小板治療ASAundTiclopidineASAundAnticoagulationASAundClopidogrelDESASA=AcetylsalicylicacidDES:Drug-elutingstentBareMetalStentPrasugrel?StentThrombosis(%)支架內血栓與抗凝、抗BMS支架內血栓發生率Days108642003060120600NEarly1.2%(N=71)Late0.4%(N=24)Studypopulation1995-2002-6,058patientsundergoingPCIwithBMSWenaweserPetal.EHJ2005N=1,191N=1,855N=361N=6,058StentThrombosis(%)BMS支架內血栓發生率Days108642003060120DES肯定的ST發生率:

Bern-RotterdamCohortStudy

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

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

Bern-RotterdamCohortStudy@4YearsWenaweserPetal.JAmCollCardiol2008,52,1134-01234TimesincePCIinyears010.52%(95%CI=0.42-0.62)/yearbetween30daysand5yearsDES肯定的支架內血栓發生率:

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支架內血栓的病因STENTTHROMBOSISStentDesign/LengthPolymerSurfaceDrugsLesionVesselSizeThrombusInterventionResidualDissectionIncompleteStentAppositionAntithromoboticMedicationPatientGeneticPolymorphismReducedLV-EFAcuteCoronarySyndromeHematologyDisorderDrugsResistanceDrug-drugInteractionDurationofAntiplateletTreatementVesselReactionVesselRemodelingHypersensitivityReactionDelayedHealing支架內血栓的病因STENTTHROMBOSISStentL支架內血栓In-Stent-Thrombosis課件早期支架內血栓的預測因素:

殘留夾層/撕裂BareMetalStentsMACE@30daysSchühlenHetal.Circulation1998N=2,894Drug-ElutingStentsMACE@30daysBiondi-ZoccaiGetal.EHJ2006N=2,418%P=0.01P=0.01ResidualDissection:IndependentPredictorofMACE(OR=2.9)早期支架內血栓的預測因素:

殘留夾層/撕裂BareMeta早期支架內血栓IVUS預測因素

WiththeUseofSirolimus-ElutingStents

FujiiKetal.JAmCollCardiol2005;45:995-8MinimalStentCSAP<0.001mm2StentExpansionResidualStenosis%P<0.001StentUnderexpansionandResidualReferenceSegmentStenosis:IndependentPredictorsofEarlyStentThrombosis!P<0.001早期支架內血栓IVUS預測因素

WiththeUse

支架內血栓預測因素

藥物反應異常

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

支架內血栓預測因素

藥物反應異常

Wenaweser服藥后血小板活性與DESST的關系

BuonamiciPetalJACC2007p<0.001p<0.001p<0.001p=ns服藥后血小板活性與DESST的關系

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過早停用抗血小板藥物是支架內血栓的重要預測因素IakovouetalParketalAiroldi支架內血栓發生時的抗血小板治療

Bern-RotterdamCohortStudy@5Years

WenaweserPetal.ESC2008支架內血栓發生時的抗血小板治療

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支架內血栓的預測因素-支架長度OR=1.02(1.00-1.04)OR=1.08(1.06-1.1)DelaTorreetalJACC2008ParketalAiroldietalIakovouRoyetalJIntervCard2007KuchulakantietalCirculation2006OR=4.4(2.0-10.0)OddsRatio支架內血栓的預測因素-分叉病變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支架內血栓的預測因素-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支架內血栓的預測因素-糖尿病IijimaAmJCard2007HR=2.2(1.1-4.3)HR=1.75(1.0-3.0)DelaTorreJACC2008KuchulakantiUrbanIakovouDaem晚期支架內血栓的可能原因ChronicinflammatoryreactiontothepolymerordrugHypersensitivitytothepolymerordrugFailureofstentstocompletelyreendothelializecompletelyLateincompletestentappositionDiseaseprogression晚期支架內血栓的可能原因Chronicinflammato多聚物高敏多聚物高敏獲得性晚期支架貼壁不良Baseline8mofollow-upSIRIUSTrial:7/80(8.7%)patients,no12-monthMACEAkoJ.etal.JACC2005;46:1002-5獲得性晚期支架貼壁不良BaselineCooketal.Circulation2007Kotanietal.JACC2006Joneretal.JACC2006Tognietal.JACC2005AbnormalVasomotionDelayedHealingDelayedEndothelializationVesselRemodeling

DES后病生理機制EndothelializationCooketal.Circulation2007Ko小結DES支架內血栓發生率：Early:0.5%-1.6%Late/Verylate:0.3%-0.6%預測因素Residualdissection,stentunderexpansionDiabetes,ACS,bifurcationstenting,stentlength,thrombusburden,lateaquiredstentmalapposition,ineffectiveplateletinhibition小結DES支架內血栓發生率：

支架內血栓的預防高危病人的辨認避免過度支架長支架,分叉支架,支架重疊支架植入的理想結果無殘留撕裂/夾層支架膨脹良好增加抗血小板治療的有效性高危病人評估抗血小板藥物的反應性再狹窄低危病人中使用BMS支架內血栓的預防高危病人的辨認專家共識FDADESPanelMeetingThereisanincreasein“verylate”(>1yr)stentthrombosisassociatedwithcurrentDES~2-4per1000ptsperyear(?continoushazard,

?patientandlesionpredictors)Datafrommultiplesourcesindicatethat

DESareassociatedwithdelayedhealing

responsesandincreasedinflammationThecausesoflateDESthrombosisaremulti-

factorial;device,procedural,andpatient

factors(oftenmultiple=perfectstorm)專家共識FDADESPanelMeetingThere專家共識FDADESPanelMeetingTheremaybealinkbetweenpost-DESreducedneo-intimalhyperplasia(lateloss)anddelayedlatehealingresponseswhichcontributestolatestentthrombosis

DESstentthrombosisishighlydefinition

dependent;needforrevisedstandardized

definitionsandadjudicationmethods(ARC)

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

inadequatecontrols;resultsinconsistent!

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

專家共識“Off-labelDESuse–incre專家共識Durationofdualanti-platelettherapyshouldextendbeyondthepresentproductlabelsOneyearisreasonablecompromise(esp.for

“off-label”DESuse)Mustbalanceagainsttheincreasedriskof

bleedingwithdualanti-platelettherapyAdditionalstudiesimmediatelyrequiredto

betterclarifyoptimalanti-platelettherapy專家共識Durationofdualanti-plat專家共識AssesspatientandlesioncharacteristicstoestablishrestenosisriskprofileDeterminerelativevalueofDESvs.BMSin

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

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

專家共識Assesspatientandlesion專家共識Assesspatientfactorswhichmayprecludelong-term(atleastoneyear)dualAPtherapyPlannedorpossibleintercurrentsurgeryBleedingHxortendenciesOtherconcomitantmedications(e.g.coumadin)Socio-economicfactorswhichmayaffectPlavixcompliance

專家共識Assesspatientfactorswhi專家共識ConsideralternativestoDES,ifris