糖尿病PCI治疗-英文课件

PercutaneousCoronaryInterventionInDiabeticPatientsS.ChiuWongMD,FACC

AssociateProfessorofMedicine

WeillMedicalCollegeofCornellUniversity

Director,CardiacCatheterizationLaboratories

TheNewYorkPresbyterianHospital-CornellCampusTheACCSymposiumattheGreatWallMeeting,BeijingChinaOctober17,2004PercutaneousCoronaryInterven1PCIinDiabeticPatients

SummaryPrevalenceofDiabetesMellitusanditsAssociatedCost?WhataretheDistinctiveFeaturesAboutDiabeticVessels?WhatistheImpactofDrugElutingStentinDiabeticPatientswithCAD?HowcouldweOptimizePCITreatmentStrategiesinDiabeticPatients?PCIinDiabeticPatients

Summ2PCIinDiabeticPatientsPrevalenceofDiabetesMellitusanditsAssociatedCosts?WhataretheDistinctiveFeaturesAboutDiabeticVessels?WhatistheImpactofDrugElutingStentinDiabeticPatientswithCAD?HowShouldweOptimizePCITreatmentStrategiesinDiabeticPatients?PCIinDiabeticPatientsPreval3PCIinDiabeticPatientsPrevalenceofDiabetesMellitusanditsAssociatedCosts?

WhataretheDistinctiveFeaturesAboutDiabeticVessels?WhatistheImpactofDrugElutingStentinDiabeticPatientswithCAD?HowShouldweOptimizePCITreatmentStrategiesinDiabeticPatients?PCIinDiabeticPatientsPreval4AccessedonOct2,2004./diabetes-statistics/national-diabetes-fact-sheet.jspSource:NationalDiabetesFactSheet(AmericanDiabetesAssociation)NationalestimatesondiabetesintheUSin2002Total:18.2millionpeople(6.3%ofthepopulation)Approximately90%ofpatientswithdiabeteshavethetype2varietywhichisassociatedwithexcessbodyfatandphysicalinactivity.PCIinDiabeticPatients

PrevalenceofDMAmongUSAdultsAccessedonOct2,2004.www.d5PCIinDiabeticPatientsDiabetes:AGeneticLegacyApproximately90%ofpatientswithdiabeteshavethetype2variety.Theincreasingprevalenceoftype2diabetescannotbedivorcedfromtherisingincidenceofobesityandphysicalinactivityinindustrializedsociety.Bothexcessbodyfatandphysicalinactivitypredisposetotype2diabetesPCIinDiabeticPatientsApprox6Mokdad,A.H.etal.JAMA2001;286:1195-1200.PCIinDiabeticPatients

PrevalenceofDMAmongUSAdults:1990vs.2000Incidenceofaself-reportofdiagnoseddiabetesincreasedfrom4.9%in1990to7.3%(49%increase)in2000.Mokdad,A.H.etal.JAMA20017Saydah,S.H.etal.JAMA2004;291:335-342.PCIinDiabeticPatients

PercentagesofAdultsWithRecommendedLevelsofVascularDiseaseRiskFactorsinNHANESIII(1988-1994)andNHANES1999-2000Saydah,S.H.etal.JAMA20048PCIinDiabeticPatients

LevelsofHbA1c,bloodpressure,andtotalcholesterolinNHANESPts

RiskfactorNHANES88-94NHANES99-2000pMeanHbA1c(%)7.67.80.30

%subjectsHbA1c<7.0%44.337.00.11

%subjectsHbA1c7.0-8.0%19.225.80.07

%subjectsHbA1c>8.0%36.537.20.87Totalmeancholesterol(mg/dL)222.8208.9<0.001

%subjects>200mg/dL66.151.8<0.001TotalmeansystolicBP(mmHg)137.9134.80.04TotalmeandiastolicBP(mmHg)73.571.50.12

%subjectswithnormalBP(SBP<130andDBP<80)29.035.80.10

%subjectswithhypertension(SBP>140orDBP>90)42.940.40.56SaydahSHetal.JAMA2004;291:335-342.PCIinDiabeticPatients

Leve9Estimatednumbersofpeoplewithdiabetesbyregionfor2000and2030andsummaryofpopulationchangesRegion(allages)#ofpeoplewithDMin2000#ofpeoplewithDMin2030%changein#ofpeoplewithDM*%changeintotalpopulation*%changeinpopulation>65*%changeinurbanpopulation*Establishedmarketeconomies44,26868,15654980N/AFormersocialisteconomies11,66513,96020–1442N/AIndia31,70579,44115140168101China20,75742,32110416168115OtherAsiaandIslands22,32858,1091484219891Sub-SaharanAfrica7,14618,64516197147192LatinAmericaandtheCaribbean13,30732,9591484019456MiddleEasternCrescent20,05152,7941636719494World171,228366,2121143713461*

Apositivevalueindicatesanincrease,anegativevalueindicatesadecrease.WildetalDiabetesCare2004;27:1047-53Estimatednumbersofpeoplewi10CountryPeoplewithdiabetes(millions)CountryPeoplewithdiabetes(millions)1India31.7India79.42China20.8China42.33U.S.17.7U.S.30.34Indonesia8.4Indonesia21.35Japan6.8Pakistan13.96Pakistan5.2Brazil11.37RussianFederation4.6Bangladesh11.18Brazil4.6Japan8.99Italy4.3Philippines7.810Bangladesh3.2Egypt6.7PCIinDiabeticPatients

Countrieswiththehighest#ofestimatedcasesofDMfor2000and2030CountryPeoplewithdiabetes(m11“…..estimatethattherewouldbe754thousandnewdiabeticsperyearin25-74yearsoldChineseifthetotalpopulationwere1.3billioninChinainthe21stcentury”HuYH,LiGW,PanXR,ZhonghuaNeiKeZaZhi.1993Mar;32(3):173-5.PCIinPatientswithDiabetesMellitus

ScopeoftheProblem“…..estimatethattherewould12糖尿病PCI治疗-英文课件13PCIinDiabeticPatientsDiabetesandCardiovascularComplicationsUKPDSInvestigatorsLancet1998;352:837PCIinDiabeticPatientsUKPDS14

KhawKTetal.AnnInternMed2004;141:413-420.PopulationRelativerisk95%CIpMen1.241.14-1.34<0.001Women1.281.06-1.32<0.001PCIinDiabeticPatientsEPIC-NorflkStudy:HemoglobinA1candMortalityIncreaseinall-causemortalityassociatedwith1%increaseinhemoglobinA1cbygenderKhawKTetal.AnnInternMed15Heartdiseaseistheleadingcauseofdiabetes-relateddeaths.AdultswithdiabeteshaveCVdeathrates~2to4timeshigherthanadultsnon-diabetics.About65%ofdeathsamongpeoplewithdiabetesareduetoheartdiseaseandstroke.PCIinDiabeticPatientsComplicationsofDiabetesinUS:HeartDiseaseandStroke

AccessedonOct2,2004./diabetes-statisticsSource:NationalDiabetesFactSheet(AmericanDiabetesAssociation)Heartdiseaseistheleadingc16Haffner,S.M.etal.NEnglJMed1998;339:229-234In1059Type2Diabeticand1378NondiabeticpatientswithandwithoutPriorMIPCIinDiabeticPatients

Kaplan-MeierEstimatesoftheProbabilityofDeathfromCADPatientswithdiabeteshavethesameriskofdeathasnon-diabeticpatientswhohavehadanpreviousMIHaffner,S.M.etal.NEnglJ17PCIinPatientswithDiabetesMellitus

ScopeoftheProblemPCIinPatientswithDiabetes18PCIinPatientswithDiabetesMellitus

ScopeoftheProblemPCIinPatientswithDiabetes19Thetotalannualeconomiccostofdiabetesin2002wasestimatedtobe$132billion,oroneoutofevery10healthcaredollarsspentintheUS.PCIinDiabeticPatients

HealthCareCostoftheDiabetesMellitusinUSThetotalannualeconomiccost20DifferencesintheDiabeticArtery:InsightsfromAngiographyandIVUSDifferencesintheDiabeticAr21PCIinDiabeticPatientsPrevalenceofDiabetesMellitusanditsAssociatedCosts?WhataretheDistinctiveFeaturesAboutDiabeticVessels?WhatistheImpactofDrugElutingStentinDiabeticPatientswithCAD?HowShouldweOptimizeTreatmentStrategiesFollowingPCIinDiabeticPatients?PCIinDiabeticPatientsPreval220102030405060SeverityIndexExtentIndexAtheromaBurdenNon-IDDM(n=57)Matchedcontrols(n=57)Pajunenetal,AmJCardiol1997;80:550-5560102030405060SeverityIndexExtentIndexAtheromaBurdenTypeI(allIDDM,n=64)Matchedcontrols(n=64)Pajunenetal,AmJCardiol2000;86:1080-1085p<0.0001p<0.0001p<0.0001p=NSp=NSp=NSSeverityindex=averageofworst%DSinLM,LAD,LCX,andRCAExtentindex=%ofcooronarysegmentsinvolvedinstenosesAtheromaburdenisbasedonsumofQCAplaqueareas/sumofQCAsegmentlengthsPCIinPatientswithDiabetesMellitus

AngiographicFindingsinDiabeticPatientsTypeIptshaveMoresevereandmoreextensivediseaseTypeIIDMptshavesimilarangiographicFindingsasnon-diabetics0102030405060SeverityIndexExte23MechanismsofRestenosisPostPCI

IVUSFindingsMechanismsofRestenosisPost24PCIinPatientswithDiabetesMellitus

Pre-interventionIVUSComparisonofDiabeticvsNon-DiabeticPatientsReferenceLesionReferenceplaqueburdenwashigherindiabetics(51%vs47%,p=0.0002)Kornowskietal,AmJCardiol1998;81:1298-1304p=0.02p=0.04PCIinPatientswithDiabetes25PCIinPatientswithDiabetesMellitus

Pre-interventionIVUSAssessmentofDiabeticPatientsAccordingtoDiseaseDurationReferenceLesion52%ofDiabetics>10yrswereinsulindependentcomparedto19%ofDiabetics<10yrs(p<0.0001)p=0.02p=0.1p=0.02p=0.003p=0.004PCIinPatientswithDiabetes26PCIinPatientswithDiabetesMellitus

Pre-interventionIVUSComparisonofInsulin-TreatedvsNon-InsulinTreatedDiabeticsReferenceLesionInsulinusewastheonlyindependent(andnegative)predictorofreferencesegmentEEM,andP&MCSAandlesionEEMandP&MCSA.p=0.015p<0.0001p=0.0063p<0.0001PCIinPatientswithDiabetes27ReferenceSegmentsMintzetal,JAmCollCardiol1995;25:1479-85Positive

remodelingIntermediate

remodelingNegative

remodelingNishiokaetal.JAmCollCardiol1996;27:1571-76LesionsReferenceSegmentsMintzetal,28PCIinPatientswithDiabetesMellitus

RemodelinginAcuteCoronarySyndromespStableACS0.0080.94±0.21.06±0.2RemodelingIndex0.00511.1±4.813.9±5.5

P&MCSA(mm2)0.31.9±0.42.3±1.1

LumenCSA(mm2)0.00413.0±4.816.1±6.2

EEMCSA(mm2)Lesion0.96.2±3.56.1±2.6

P&MCSA(mm2)0.067.9±2.89.1±3.6

LumenCSA(mm2)0.214.2±5.215.2±5,2

EEMCSA(mm2)ProximalreferenceSchoenhagenetal.Circulation2000;101:598-603Remodelingp<0.0001PCIinPatientswithDiabetes29PCIinPatientswithDiabetesMellitus

DiabetesModulatesRemodelinginACSandStableAngina(n=927)DMNoDMAcuteCoronarySyndrome59/183(32.0%)225/469(48.0%)StableAngina17/88(19.6%)42/187(22.3%)Abizaid,unpublishedobservationsFrequencyofPositiveRemodelingPCIinPatientswithDiabetes30PCIinPatientswithDiabetesMellitus

InteractionofDiabetes,VesselSize,FinalMLD,andMultipleStentsonRestenosisPost-stenting0.60.40.202345DiabeticsNon-DiabeticsProbabilityofRestenosisVesselSize(mm)Elezietal.JAmCollCardiol1997;30:1428-36Elezietal.JAmCollCardiol1998;32:1866-73Probability&PredictorsofRestenosisPCIinPatientswithDiabetes31PCIinPatientswithDiabetesMellitus

IVUSfindingsindiabeticvsnon-diabeticptsinnon-stentedlesionsWHCp=NSOARSp=0.072p=0.19p=0.0392∆

EEMCSA(mm2)∆

P&MCSA(mm2)∆

EEMCSA(mm2)∆

P&MCSA(mm2)∆EEMCSAcorrelatedwith∆P&Minnon-diabetics,butnotindiabeticsindicatingthatdiabeticslackedtheabilitytorespondtotheexaggeratedintimalhyperplasiathatisalsopresentPCIinPatientswithDiabetes32PCIinPatientswithDiabetesMellitus

IVUSFindingsinDiabeticvsNondiabeticPatientsPostStentKornowskietal.Circulation1997;95:1366-9p=0.0009p=0.0007mm2PCIinPatientswithDiabetes33PCIinPatientswithDiabetesMellitus

InfluenceofDiabetesonEarlyandLateOutcomeAfterPTCASteinetal.Circulation1995;91:979-9895-yeareventratesIndependentpredictorsof5-yearsurvivalindiabeticpatientswereyoungerage,absenceofheartfailure,preservedLVfunction,absenceofmultivesseldisease,andnon-insulindependentP<0.001P<0.001P<0.001P<0.001PCIinPatientswithDiabetes34PCIinPatientswithDiabetesMellitus

NHLBIPTCARegistry:DiabeticPatientsKipetal.Circulation1996;94:1818-18259-yeareventratesP<0.001P<0.001P<0.001P<0.05PCIinPatientswithDiabetes35PCIinDiabeticPatients

Impactofrestenosisanddiseaseprogressiononclinicaloutcome14monthsaftermultivesselstentingLoutfietal.CathCardiovascIntervent2003;58:451-4PCIinDiabeticPatients

Impac36PCIinPatientswithDiabetesMellitus

Roleofvesselsizeaspredictorforin-stentrestenosisindiabeticpatients

p=0.002Suslbecketal.AmJCardiol2001;88:243-7RestenosisratesPCIinPatientswithDiabetes37PCIinDiabeticPatients

SummaryonDiabeticVesselsDiabeticshavemorediffuseatherosclerosisand(perhaps)smallerlumendimensionsIncreasedplaquemassespeciallyinnon-insulintreatedpatientsImpairedremodelingresponses,especiallyininsulin-treatedpatientsDiabeticshaveincreasedriskofrestenosispost-PCI(bothstentornon-stent)SmallerfinallumendimensionsMoreintimalhyperplasiainbothstentandnon-stentinterventionsImpairedremodelingresponsesinnon-stentinterventionsDiabeticshaveincreasedriskofdeath/MI/PCIofnewlesionsIncreasedplaqueburden?MoreunstableplaquemorphologiesPCIinDiabeticPatients

Summ38Smalldiameterlesions 30-40%Longlesions 37-50%Diabetes 26-46%Ostiallesions 40-50%Bifurcatedlesions 40-60%Source:KalanHo,andPCR2000marketresearch.CoronaryStents

RestenosisPostStentinHigherRiskPatient/LesionSubsetsStentisnopanacea…Smalldiameterlesions 30-40%39PCIinDiabeticPatientsPrevalenceofDiabetesMellitusanditsAssociatedCosts?WhataretheDistinctiveFeaturesAboutDiabeticVessels?WhatistheImpactofDrugElutingStentinDiabeticPatientswithCAD?HowShouldweOptimizeTreatmentStrategiesFollowingPCIinDiabeticPatients?PCIinDiabeticPatientsPreval40Cost-effectiveness(1,000s)canvarydramaticallyinpatientstakinglovastatinforprimaryprevention.

PCIinDiabeticPatients

DiabeticSubsetinthe4SStudyPyoralaKetal.DiabetesCare1997;20:614-20Cost-effectiveness(1,000s)ca41PCIinDiabeticPatients

SIRIUS:MultivariablePredictorsforIn-segmentRestenosis<12mm12-15mm>15mm>3.0mm3.43.94.92.5-3.0mm5.66.47.9<2.5mm8.29.411.5LesionLength<12mm12-15mm>15mm>3.0mm7.88.910.92.5-3.0mm12.414.017.0<2.5mm17.719.823.7LesionLengthRefDiamRefDiamNon–DiabeticDiabeticPCIinDiabeticPatients

SIRI42

PCIinDiabeticPatients

Studiesincludedinthemeta-analysis

DawkinsK.ESCCongress2004;August28-September1,2004.StudyOverallpatientsDiabeticpatientsInsulin-treatedpatientsTAXUSIIslowrelease266307TAXUSIImoderaterelease263217TAXUSIVslowrelease1314318105TAXUSVImoderaterelease4468935Overall2289458(Controls=242;TAXUS=216)154(Controls=83;TAXUS=71)PCIinDiabeticPatients

Stu43

p=nsp=0.0001p=ns*incl.CABGe-CYPHER:DMSubgroupMACE&TLR@6-monthFUN=2716Ptsp=nsp=0.0001p=ns*incl.44RAVEL-DiabeticSubgroup

Sirolimus Control N=19 N=25 pLesionlength(mm) 9.74 9.42 NSRef.Vesseldiameter(mm) 2.52 2.51 NSMLD(mm) Pre 0.99 0.93 NS Post 2.37 2.36 NS FU 2.31 1.56 <.0001Lateloss(mm) 0.08 0.82 <.0001Latelossindex 0.05 0.57 <.0001DS(%) FU 16 38 <.0001Restenosisrate(%) 0 42 <.0001TLR-PCI(%) 0 32.0 0.007TotalMACE(%) 10.5 48.0 0.01RAVEL-DiabeticSubgroup Siro45SIRIUS:ClinicalOutcomesinDiabeticSubgroupSirolimus(n=131)Control(n=148)P-valueLateloss(mm)in-stent0.291.20<0.001in-segment0.401.00<0.001Restenosis(%)in-stent8.348.5<0.001in-segment17.650.5<0.001TLR(%)6.922.3<0.001MACE(%)9.225.0<0.001Lesionlength=14.5mmandReferencevesselsize=2.75mmAt9monthsSIRIUS:ClinicalOutcomesinD4673%

p=0.01583%

p<0.0013/3715/555/15828/143NewSIRIUS

-DiabeticSubgroup9-monthTLR73%83%3/3715/555/15828/147PCIinDiabeticPatients

Latelossobservedinthemeta-analysis

DawkinsK.ESCCongress2004;August28-September1,2004PatientsubgroupIn-stentlateloss(mm)pNondiabeticpatients

<0.0001Bare-metalstent(n=609)0.86+0.54

Paclitaxel-elutingstent(n=603)0.36+0.47

Oral-agents-onlydiabeticpatients

<0.0001Bare-metalstent(n=79)1.03+0.58

Paclitaxel-elutingstent(n=91)0.36+0.51

Insulin-treateddiabeticpatients

0.0006Bare-metalstent(n=48)1.01+0.53

Paclitaxel-elutingstent(n=44)0.33+0.50

PCIinDiabeticPatients

Late48ReviewofDrug-elutingStentsinDiabetes:IDDMPatientsn=54n=5142.97.7p=0.007TAXUSIVDIRECTTAXUSIVdiabetics*TAXUS:9monthanalysis;SIRIUS:8monthanalysisControlBMSTAXUSDESCYPHERDESAngiographicrestenosis*(mm)706050403020100Insegmentrestenosisrates:insulin-req.diabeticpatientsn=3835.0n=140.0DIRECT–DiabeticSubgroupAnalysis

SignificantreductioninrestenosiscomparedtohistoricalSIRIUSIDDMpatients,attributedtoimprovedoperatortechniquep=0.03BxVelocityReviewofDrug-elutingStents49DIABETesandsirolimusElutingStentThe

DIABETES

TrialDIABETesandsirolimusEluting50DIABETES:BackgroundDiabeticpatientsexhibitahigherincidenceofrestenosis/MACEafterPCIascomparedtonon-diabeticpopulation.Sirolimuselutingstentshavedemonstratedtobeeffectiveforthetreatmentofcoronarystenosesoflow-to-moderaterisk.Subgroupanalysesfromrandomizedtrials(RAVEL,SIRIUS)haveshownabeneficialeffectofthesestentsindiabeticpatients.HYPOTHESIS: Sirolimuselutingstentreducesthedegreeofneointimalhyperplasiaafterstentingindiabetics.DIABETES:BackgroundDiabetic51DIABETESTrial:Objective

Toassesstheefficacyofsirolimuselutingstent

followingsuccessfulcoronarystentimplantationindiabeticpatientswithdenovocoronarystenoses.DIABETESTrial:ObjectiveToa52DIABETES(DIABETesandsirolimusElutingStenttrial)Multicenter,Prospective,Randomized.

1-Madrid.H.SCarlos(DrSabaté,PI)2-Barcelona.H.Bellvitge(DrGómez-Hospital)3-Valladolid.H.Clínico(DrFernández-Avilés)4-Vigo.HdoMeixoeiro(DrGoicolea)....2134Noofficialsponsor:grantfromCordis-SpainSpanishSocietyofCardiology2003grantDIABETES1-Madrid.H.SCarl53Typeofstudy&PrimaryEndpoint-Multi(4German)-center,prospective,randomized(computer),placebo-controlledtrial.-Sub-randomizationaccordingtothetypeofdiabetes.PRIMARYENDPOINT:-In-Stent+edges(in-segment)latelumenlossasassessedbyQCAat9-monthangiographicfollow-up.Typeofstudy&PrimaryEndpoi54SecondaryEndpoints&SamplesizeSECONDARYENDPOINTS -OtherQCAparameters(restenosis,MLD)atFU. -Meanin-stent+edgesneointimalhyperplasiaand% volumeobstructionbyIVUSat9-monthfollow-up. -MACE(cardiacdeath,MIandTLR)at30d,9,12and24 months. -Developmentofcomplications:aneurysmformation, latethrombosis,edgeeffect,latestentmalapposition.SAMPLESIZE -160patients(80SES;80BMS). (56%differenceinlatelumenloss:estimatedforaLLLof 0.73mminBMSto0.32mminSES;SD0.70,alfaerrorof 0.05,betaerrorof0.10and10%missingvalues).SecondaryEndpoints&Samples55DIABETES:Inclusioncriteria

Diabeticpatient(non-insulindependentorinsulindependent)accordingtoWHO1999Report.Coronarylesionsinnativecoronaryarteriesandsymptomsorobjectiveevidenceofischemia.LesionfavourableforPTCA+stentimplantation.Informedconsent.DIABETES:InclusioncriteriaD56DIABETESTrial:Exclusioncriteria

Diabeticpatientwithoutpharmacologicaltreatment(ondiet).Stenoseslocatedintruebifurcations,SVG,LIMAorunprotectedleftmain.In-stentrestenosis.Chronicrenalorhepaticinsufficiency.PreviousbrachytherapyorDESimplantation.RecentAMI(<72h)with

CPK(x2).Malignancy.DIABETESTrial:Exclusioncrit57901non-diabetics3otherprotocol147ExclusionCriteria2Logistics/Operator80PatientsSES9-monthangiographicFU80PatientsBMS163PatientsEligible1216PatientsUndergoingPCI9-monthangiographicFUFailuretocrossCTODIABETESSTUDYFLOWCHARTREGISTRY153P(48%)(52%Randomized)1-yearclinicalFU1-yearclinicalFU1-monthclinicalFU1-monthclinicalFU160PatientsRandomizedInclusionCriteriaInformedConsentRxCentralized(computer)SubRx:typeofdiabetesQCAPrimaryEnd-pointAbciximab+ASA100-300mg/day+Clopidogrel75mg/day(atleast1year)Feb03-Nov03901non-diabetics3otherproto58FlowChart:160PtsRandomizationInclusionCriteriaInformedConsentRxCentralizedSubRx:typeofDM80ptsSES80ptsBMS110lesions9MoAngioFU

102les(92%)80ptsCypher111lesionsDIABETES2cardiacdeaths8missing1cardiacdeath4missing9MoAngioFU100les(91%)FlowChart:160PtsRandomizati59QCAanalysis

QCAanalysis60DIABETES

BaselineCharacteristicsSES

n=80BMS

n=80Age,y65.9±8.867.2±9.6Male,n(%)50(62.5)50(62.5)IDDiabetes,n(%)26(32.5)27(33.7)NIDDiabetes,n(%)54(67.5)53(66.3)Hypertension,n(%)53(66.3)53(66.3)Tobaccouse,n(%)36(45)40(50)Dyslipidemia,n(%)49(61.3)49(61.3)PreviousMI,n(%)25(31.3)34(42.5)PreviousPTCA,n(%)14(17.5)11(13.8)PreviousCABG,n(%)2(2.5)3(3.8)MultivesselDisease,n(%)49(61.3)55(68.8)EjectionFraction,%66.9±13.163.5±13.9p=NSDIABETESBaselineSESBMSAge61ClinicalPresentationSESgroup(n=80)BMSgroup(n=80)p=NS45%30%10%5%35%8.8%12.5%30%10%13.7%ClinicalPresentationSESgroup62Locationofstenoses11.7%3.6%1.4%20.7%16.7%9.5%14%0.5%9.9%2.7%5.9%0.5%1.8%0.9%Locationofstenoses11.7%3.6%163LesioncharacteristicsReferencediameter201030401,02,03,04,00FrequencyMean:2.34±0.6mmp=0.082.212.262.332.352.382.40p=NSLesioncharacteristicsReferenc64Lesioncharacteristics*Excludingchronictotalocclusionsp=NSforallvariables

Alllesions(n=221)SES(n=111)BMS(n=110)Lesionlength*,mm14.5±8.215.3±7.6Referencediam,mm

2.33±0.52.35±0.5B2/C,n(%)89(80.2)88(80)Calcification,n(%)46(43.4)39(35.8)Totaloccl,n(%)14(12.6)15(13.6)15.0±8.12.34±0.6177(80.1)85(38.5)29(13.1)Lesioncharacteristics*Exclud65Studiesbylesionlength,vesselsizeand%diabeticsSIRIUS2.802.75

Lesionlength(mm)Referencediameter

8 10 12 14 16 18 20 22mm2.55TAXUSIITAXUSIVTAXUSVIRAVELNewSIRIUS2.702.602.502.402.452.352.30mmPACLITAXELRAPAMYCINLESIONLENGTHREFERENCEDIAMETER18%15%24%26%20%23%DIABETES*100%*13%ChronictotalocclusionsStudiesbylesionlength,vess66ProceduralCharacteristicsDIABETESTreatedartery,%LAD/LCX/RCA

39/21/40

44/23/33Multivesselstent,%2324Multisegment,%1611N.stenosis/patient1.4

0.61.4

0.5N.stent/patient1.6

0.81.7

0.9Stentlength,mm22102313IIb/IIIainhibitors,%6454SES(n=111)BMS(n=110)p=NSforallvariablesProceduralCharacteristicsDIA67Death,n(%)0(0%)2(2.5%)nsQ-MI,n(%)0(0%)0(0%)nsNon-QMI,n(%)0(0%)3(3.8%)nsTLR/TVR,n(%)0(0%)0(0%)nsMACE,n(%)0(0%)5(6.3%)0.1SES(n=80)BMS(n=80)pOne-monthClinicalOutcomes**1cardiacrupture;1suddendeath†CPK<600;n<190†Death,n(%)0(0%)2(2.5%)nsQ-68In-stentProximaledgeDistaledge0.08±0.40.66±0.5

88%p<0.0001mmp=NSp=0.1PrimaryEndpoint:InStent

LateLumenLossat9-monthFUIn-stentProximaledgeDistale690.08±0.40.44±0.5mm

82%p<0.0001In-segmentanalysisSESBMSPrimaryEndpoint:In-segment

LateLumenLoss@9-monthFU0.08±0.40.44±0.5mm82%p<070SESBMSSecondaryEndpoint:RESTENOSISRATEat9-monthFUIn-stentProximalDistal5(4.9%)31(31%)

84%p<0.0001%p=nsp=ns1%2%1%1%8(7.7%)33(33%)%

76%p<0.0001In-segmentanalysisSESBMSSecondaryEndpoint:REST71SESBMS%PrePostCFDCurves-In-SegmentMLDmmMLDSESBMS%PrePostCFDCurves-I72SESBMS%PrePostCFDCurves-In-SegmentMLDmmFupMLDSESBMS%PrePostCFDCurves-I73AllOralagentInsulin-dependentLATELOSSANDDIABETESSTATUSSESBMSmm0.440.410.500.080.11-0.001p<0.0001forallgroups

82%

99%

72%AllOralagentInsulin-dependen74Cardiacdeath,n(%)1(1.3%)2(2.5%)nsQ-MI,n(%)1(1.3%)0(0%)nsNon-QMI,n(%)1(1.3%)5(6.3%)nsTLR(in-segm),n(%)6(7.5%)25(31.3%)<0.0001MACE,n(%)(exclusiveevents)9(11.3%)29(36.3%)<0.0001SES(n=80)BMS(n=80)p9-monthClinicalOutcomesCardiacdeath,n(%)1(1.3%)2(27501234567890100Time(months)%Breslowtestp=0.00563.7%88.7%SESBMSDIABETES:%FreedomFromMACE5001234567890100Time(months)%Br76Conclusions(I):

Thisrandomizedtrialhasdemonstratedthattheuseofsirolimus-elutingstentindiabeticpatientseffectivelyreducedin-segmentlatelumenlossandrestenosisrate,ascomparedwithbaremetalstent.Thisbeneficialeffectledtoasignificantreductionintheneedforrepeatrevascularizationat9-monthfollow-up.Conclusions(I):Thisrandomiz77DIABETES:Conclusions(II):

Insulin-dependentdiabeticstreatedwithsirolimusstentimplantationexhibitedthesamedegreeofreductioninrestenosisparametersascomparedwiththosetreatedwithoralagents.Rapamycinstentimplantationindiabeticsappearedtobesafeasnolatestentthrombosesoccurredat9-monthfollow-up(onclopidogreltreatment).DIABETES:Conclusions(II):In78CYPHERinDiabeticPatients%TLR030RAVEL

12mos.100%CYPHERStent:ClinicalDatainDiabeticPatients(1-5)TLR2010SIRIUS

12mos.68%NewSIRIUS9mos.73%e-CYPHER

6mos.Patients(n)MLDpost(mm)StentedLength(mm)192.4318.1RAVEL(1,2)1312.6221.5SIRIUS(3)NewSIRIUS(4)452.4523.3e-CYPHER(5)3171p<0.0001p<0.001p<0.0011.MCMorice,PresentedatESC2001.2.A.Colombo,PresentedatESC2002.3.SIRIUSresultspresentedatTCT2002.4.NewSIRIUSresultspresentedatTCT2003.5.G.Guagliumie-CYPHERresultsTCTandAHA2004.2.8*20.3*VisualorQCAestimation?53881017IDDMPatients(n)CYPHERinDiabeticPatients%T79Post-marketingsurveillanceregistrytodetermine:SafetyofSESinroutineclinicaluseReproducibilityofRCTresultsIdentificationofMACEpredictorsBothon-andoff-labelusewererecordedClinicalFUatone,sixandtwelvemonthsNomandatoryangiographicfollow-upTargetrecruitement=15,000patients

e-CypherRegistry:GoalsanddesignPost-marketingsurveillancere80E-CypherRegistry-EnrolledPatients29%14.515patientsEnrollementnowconcludedFollow-upstillongoing...E-CypherRegistry-EnrolledP81IndependentAdvisoryBoardIndependentEndpointCommittee(ChairM.Bertrand)Independentdatamanagement(Eminent-PPD)Independentdataanalysis(HesperionLtd)Audit:ongoingcheckofca.3%ofentriesagainstpatientchartandPCI