非ST段抬高急性冠脈綜合征課件

1.7MillionHospitalDischarges

AHA.HeartDiseaseandStrokeStatistics—2005UpdateACSSTEMIHospitalDischargesforACS

Non-STEACSvsSTEMINSTEACS1.4MillionDischarges/Yr321,000Discharge/YrNSTEACS:KeyThemesNSTEACS:ahighriskpopulationpatientriskbenefitfromtreatmentwithmedications,aninvasivestrategyInteractionbetweeninvasivestrategyandpharmacologictxAntithromboticscornerstoneoftreatmentAnticoagulants:heparin,LMWH,directthrombininhibitorsAntiplateletagents:aspirin,IIb/IIIa,ADPinhibitorsBaselineCharacteristicsNSTEACSPatients:

RecentRCTsandLargeRegistry

Q22003

PURSUIT

CURE

GUSTO-IVACS CRUSADE

Characteristic

(n=9,461) (n=12,562) (n=7,800)(n=5,426)Meanage±SD(yrs) 63±11 63±12 65±11 67±14Diabetesmellitus(%) 23 23 22 33PriorCHF(%) 11 8 8 19PriorPCI(%) 13 --- 10 22PriorCABG(%) 12 18* 8 20NEJM1998;339:436;NEJM2001;345:494;Lancet2001;357:1915-24*CABGorPTCAAntmanEMetalNEnglJMed1996;335:1342-9360240120020181614121086420Cumulativeprobabilityofdeath>84ml/min51-66ml/min<51ml/minP<0.001,logrank%66-84ml/min

AvilesRJetalNEJM2003CreatinineClearanceandMortalityGUSTO4Days360240120020181614121086420Probabilityofdeath,%>1869ng/L237-669ng/L<237ng/LP<0.001,logrank

669-1869ng/LJamesSetalCirculation2003NT-proBNPGUSTO4DaysInvasivevs.ConservativeStrategyforACS

Deathor(re)-MI

TrialNPCIConsRITA318107.68.3VINO1316.322.4TACTICS22207.39.5TRUCS1487.616.7FRISCII245110.414.1MATE2019.96.7VANQUISH92024.012.2Overall7876Fox,Lancet360:743‘03Death/(re)Infarction

RR=0.88,p=0.05Interventionbetter

0.10.20.30.50.71.01.52.0Death/(re)-MICP971744-45%ConsInvTACTICS–TIMI18TnTcutpoint=0.01ng/mL(54%ofptTnT+)TroponinT:Death,MI,RehospACS,6MonthsOR=0.52*P<0.001InteractionP<0.001P=NS*n=414n=396n=463n=495FRISCScoreandanInvasiveStrategyScore0-23-45-7n9721051264p0.560.018<0.001RR1.14(0.73-1.77)0.69(0.50-0.94)0.44(0.28-0.69)0510152025303540DeathorMIat12mos,%Strategy:Non-invasiveInvasiveFRISCscoreAge>65yearsMalegenderDiabetesmellitusPreviousMIST-depressionElevatedtroponinElevatedIl-6/CRP

LagerqvistBetalHeart2004BenefitsofanInvasiveStrategyinNon-STElevationACS

OnlyshowntoreducedeathandMIin highriskptsReducesre-hospitalization,anginain manyothersShortenshospitalization,maybecost effectiveWhatabouttheoptimaltimingofan invasivestrategy?MedicalTxfor72-170hrThen,cathlabn=207Cathlab6hrn=203ISAR-COOLCP1107655-4NeumannFJetalJAMA2004

67%hadtroponin,65%hadSTdepression

Aspirin 500mg,100mgbid

Clopidogrel 600mg,75mgbid

Tirofiban 10mg/kgbolus,0.10mg/kg/mininfusion

Heparin (PTT60-85seconds)Non-STAcuteCoronarySyndrometroponinorSTdepressionn=410ISAR-COOL

PrimaryEndpointCP1107655-230-dayeventrate(%)

Death&MI

DeathNeumannFJetalJAMA2004P=0.04P=0.23P=0.12P=0.56

AnynonfatalMINonfatalQ-waveMIRR1.96(1.01-3.82)

Coolingoff(n=207)

Earlyintervention(n=203)ISAR-COOL

FrequencyofEventsBefore,AfterCatheterizationCP1107655-3DeathandMI(%)

BeforeDuringandAfterNeumannFJetalJAMA2004P=0.002P=0.96

Coolingoff(n=207)

Earlyintervention(n=203)

CatheterizationTimingofanInvasiveStrategyinNon-STElevationACS

ISAR-REACTwasasmall,single centerstudyOtheranalysesalsoindicatethatcath within24hoursisbetterthanlatercathOughttouseintensiveantiplatelet therapywithaveryearlyinvasivestrategyWhatmedicaltherapyoughttobeusedinACS?66-84ml/minPlacebo(n=6,303)CURE:AspirinDoseandOutcomeTimetocath* 22 21

(hours) (6,44) (6,43)Clopidogrel(n=6,259)TENACITY

StudyMedicationDosageStratifiedbyIIb/IIIausePatients(%)Placebo(n=6,303)PlaceboinACSTirofiban(n=189)25μg/kgbolus5%) 104/1412(7.AllACStrials 24,311 0.AntiplateletBetterDischarges/YrEnoxaparin UFH

(n=4993) (n=4985) P-valueHeparinbetter*CABGorPTCA125μg/kg/min(≤10mcg/min)x12hoursAntithromboticTrialists’Collaboration.BMJ.2002;324:71–86.

OR*0.51.01.52.0500–1500mg 34 19160–325mg 19 2675–150mg 12 32<75mg 3 13Anyaspirin 65 23AntiplateletBetterAntiplateletWorse

AspirinDose No.ofTrials (%)OddsRatio0AspirinDoseandEventsinHigh-RiskPts

FrequencyofCVDeath,MI,StrokeP=0.0001CURECP999547-2YusufSetalNEJM2001;16:494-502Non-STelevationACS12,562patientsASA75to325mgpoqdplacebon=6,3033-12monthfollow-up(average9mo)ASA+clopidogrel(300mgload,75mgqd)n=6,259CURE:AspirinDoseandOutcome

%(N=1,927)(N=7,428)(N=3,201)

ASA/ClopidogrelASA/Placebo

CVDeath,MI,Stroke

MajorBleedingAspirininACSMorebleedingwithhigherdoses,especiallywhencombinedwithclopidogrel,coumadinPossiblygreaterefficacywithlowerdoses(notsure)Irecommend:<165mgoncedailyGuidelines:stillrecommend81-365mgaspirinCURE

CVDeath/MI/Stroke,1YearCP999731-3CVdeath,MI,stroke(%)Clopidogrel(n=6,303)Placebo(n=6,259)P=0.00003DaysafterenrollmentCUREEvent

rate

(%)RR0.80P=0.00005CP995058-6CVdeath,

MI,strokeClopidogrel(n=6,259)Placebo(n=6,303)AspirinandCV

deathMIStrokeNon-CV

deathRR0.92P=NSRR0.77P<0.001RR0.85P=NSRR0.96P=NSRestrictedtheparticipationofhospitalsthatpursueaninvasivestrategyinthemajorityofACSptsTheresultsoughttobeappliedtoptsthatresemblethoseenrolledinthetrialThereisreasontobelievethatearlydualantiplatelettherapymighthavedifferentsafety,efficacyininvasivevs.non-invasivelymanagedptsCURECURE

Major/Life-ThreateningBleedsinthe7DaysAfterCABGPlaceboClopRRpStopped<5dayspriortoCABG:N=476N=436PtswithMajororLifeThreateningBleeding6.3%9.6%1.530.06MajorBleeds:

Significantlydisabling,intraocular,ortransfusion2unitsLifeThreatening:Hgb>5g/dl,hypotension(inotropes),surgerytostopbleeding,symptomaticICHortransfusion4unitsACC/AHAACSGuidelineUpdateClassIASAandclopidogrelfor9monthsafterNSTEACS(levelofevidence:B)Class3Donotadministerclopidogrelinthe5daysbeforeCABG BraunwaldE,etal.IVEnoxaparinElevatedIl-6/CRP30-DayClinicalOutcome4%) 7/189(3.Anticoagulants:heparin,LMWH,directthrombininhibitorsReduceheartrate,bloodpressure,ischemia,chestdiscomfortProbability25mg/kgbolus5%) 104/1412(7.CP1107655-3Abciximab(Reopro)Invasivevs.Threatenedabruptclosure(%) 1.HeartDiseaseandStrokeElevatedIl-6/CRPOnlyshowntoreducedeathandMIin highriskptsPriorPCI(%) 13 --- 10 22ConservativeStrategyforACS

Deathor(re)-MIEnoxaparin UFH

(n=2321) (n=2364)SYNERGY

DeathorMIat30DaysHeparin(UForLMW)inACSWithoutST

DeathorMI

UFHorLMWH

Control

OR 95%CITheroux 2/122(1.6%) 4/121(3.3%) 0.50 0.10-2.53Cohen 0/37 1/32(3.1%) 0.12 0.01-5.89RISC 3/210(1.4%) 7/189(3.7%) 0.40 0.11-1.39Cohen 4/105(3.8%) 9/109(8.2%) 0.46 0.15-1.41Holdright* 42/154(27.3%) 40/131(30.5%) 0.85 0.51-1.43Gurfinkel 4/70(5.7%) 7/73(9.6%) 0.58 0.17-1.98

(UFH)Gurfinkel 0/68 7/73(9.6%) 0.13 0.03-0.60

(LMWH)FRISC 4/70(5.7%) 36/757(4.8%) 0.39 0.22-0.68UFHvs 55/698(7.9%) 68/655(10.4%) 0.67 0.45-0.99

placebo/controlLMWHvs 13/809(1.6%) 43/830(5.2%) 0.34 0.20-0.58

placeboTotal

68/1507(4.5%) 104/1412(7.4%) 0.53 0.38-0.73OnlyRCTs,placebooruntreatedcontrols

EikelboomJWetal:Lancet55:1936-42,2000CP951342-10.1Heparinbetter1.010.0Controlbetter

Enoxaparin UFH

(n=4993) (n=4985)Cathduringhosp(%) 92

92Timetocath* 22

21

(hours) (6,44) (6,43)PCI 47 47TimetoPCI* 23 22

(hours) (6,49) (6,48)CABG(%) 19 18TimetoCABG* 91 89

(hours) (44,167) (45,166)Dayshospitalized* 5 4

(3,8) (3,8)In-hospitalProcedures*Median(25th,75th)SYNERGY

DeathorMIat30Days0510152025300.80.850.90.951.0FreedomfromDeath/MIDaysfromRandomizationUFHEnoxaparinHR0.96(0.86-1.06)1.1SYNERGY

BleedingEvents

Enoxaparin UFH

(n=4993) (n=4985) P-valueGUSTOsevere 2.9 2.4 0.107TIMImajor-clinical: 9.1 7.6 0.008

CABG-related 6.8 5.9 0.081

Non-CABG-related 2.4 1.7 0.025AnyRBCtransfusion 17.0 16.0 0.155ICH <0.1 <0.1 NSPCIPatients:ThromboticComplications

Enoxaparin UFH

(n=2321) (n=2364)UnsuccessfulPCI(%) 3.6 3.4Threatenedabruptclosure(%) 1.1 1.0Abruptclosure(%) 1.3 1.7EmergencyCABG(%) 0.3 0.3ElectivePCIviaFemoralRouteN=3528IVEnoxaparin0.5mg/kgbolusIVHeparin70-100U/kgw/oIIb/IIIA(ACT300-350)50-70U/kgwithIIb/IIIa(ACT200-300)STEEPLEIVEnoxaparin0.75mg/kgbolusStratifiedbyIIb/IIIauseMontalescotGESC2005

STEEPLE

Bleedingat48Hrs(PrimaryEndPoint)P=0.007P=0.005P=0.315P=0.530–57%1.24.92.85.41.25.9MajorbleedingMinorbleedingP=0.007P=0.005P=0.315P=0.530–57%1.24.92.85.41.25.9MajorbleedingMinorbleedingP=0.052P=0.0146.06.68.7012345678910MinorormajorbleedingPatients(%)P=0.052P=0.0146.06.68.7012345678910MinorormajorbleedingPatients(%)Enoxaparin0.5(n=1046)Enoxaparin0.75(n=1206)UFH(n=1212)MontalescotGESC2005STEEPLE

IschemicEndPointsat30DaysMontalescotGESC2005Trial: FRIC(dalteparin;n=1482)FRAXIS(nadroparin;n=2357)ESSENCE(enoxaparin;n=3171)

TIMIIIB(enoxaparin;n=3910)

.75 1.0 1.5(P=0.032)(P=0.029)BraunwaldEetal.Circulation2000;102:1193-1209LMWHBetterUFHBetterLMWHversusUFHinUA/NSTEMIManagedNon-invasively:

EffectonDeath,MI,RecurrentIschemiaGUSTOsevere 2.PlaceboinACSPriorPCI(%) 13 --- 10 22DouseaDTIinACSptswith heparininducedthrombocytopeniaTimetocath* 22 21

(hours) (6,44) (6,43)LMWHvs 13/809(1.EmergencyCABG(%) 0.ACC/AHAACSGuidelineUpdate8%) 9/109(8.WhatmedicaltherapyoughttobeusedinACS?HeparinbetterPlaceboinACSASA+clopidogrelFreedomfromDeath/MILMWHversusUFHinUA/NSTEMIManagedNon-invasively:

EffectonDeath,MI,RecurrentIschemiaFRISC 4/70(5.HeparinbetterDaysafterenrollmentPCIPatients:ThromboticComplications(N=3,201)Restpain>5minandSTΔ>0.1mVorDocumentedCADorCK-MBN=132Heparin70U/kgbolus+15U/kg/hrinfusion

Bivalirudin0.1mg/kgbolus+0.25mg/kginfusionTIMI-8:Bivalirudinvs.PlaceboinACSTIMI-8:Bivalirudinvs.PlaceboinACS4-6wks7days4-6wks7daysp=0.008p=0.024p=NSp=NSDirectThrombinInhibitorsinACSCP999731-7

Beingstudied;currentlylittledataDouseaDTIinACSptswith heparininducedthrombocytopeniaBivalirudinifaninvasivestrategyis planned(safebutnotapprovedfor HIT)Lepirudinifanon-invasive strategyisplanned(approved forHIT,notapprovedforPCI)BetaBlockersReduceCVdeath,MI,strokeby25-30%inhighriskptsNotwellstudiedinnon-STEACSReduceheartrate,bloodpressure,ischemia,chestdiscomfortClass1indication;qualityindicatorUseineveryonewithoutcontraindications15.75.617.911.712.814.23.812.910.311.805101520PrimaryEndpoint%PlaceboGPIIb/IIIaPURSUIT

30daysPRISM

48hrsPRISM

PLUS

7daysP=0.04P=0.01P=0.004PARAGONA

30daysP=0.48PARAGONB

30daysP=0.33PlateletGPIIb/IIIaInhibitionforNon-STACS

PrimaryEndpointResultsfromthe5MajorRCTs1.02.00.25AllPCItrials 17,393 0.66 8.5 5.6AllACStrials 24,311 0.89 12.8 11.4ACStroponin(+) 1,368 0.42 16.3 6.9ACSPCI 2,311 0.66 14.4 9.6ACSnoPCI 12,685 0.93 14.3 13.3ACStroponin(–) 2,901 1.05 6.2 6.5IIb/IIIaMeta-Analysis

30-DayDeath,MIat30DaysCP944328-1

Relative

risk Placebo IIb/IIIa

No. ratio (%) (%)ChewDPetal:JACC2000;36:2028–35IIb/IIIabetterPlacebobetterIIb/IIIaInhibitorsinACSPatientsGreatestbenefitisduringPCIIfpursuinganon-invasivestrategy,recommendtreatingptswithelevatedtroponins,highTIMI,FRISCscores,etc;probablythosewithdiabetes,markedSTsegmentshiftsDonotrecommendtheirroutineadministrationtoallACSptsinwhomanon-invasivestrategyisplannedTENACITY

TirofibanEvaluationofNovelDosingvs.AbciximabwithClopidogrelandInhibitionofThrombinStudyIntermediatetoHigh-riskPCIPatientsAspirin+High-doseClopidogrelIntent-to-stentN~8,000TirofibanAbciximabHeparinBivalirudinHeparinBivalirudinStoppedafter383ptsenrolledTENACITY

StudyMedicationDosageTirofiban(Aggrastat)25μg/kgbolus0.15μg/kg/mininfusionx12hoursAbciximab(Reopro)0.25mg/kgbolus0.125μg/kg/min(≤10mcg/min)x12hours(N=1,927)lowriskptsTotal 68/1507(4.Non-CV

deathTENACITY

TirofibanEvaluationofNovelDosingvs.AntiplateletBetter15μg/kg/mininfusionx12hoursPlacebo(n=6,303)001,logrankPARAGONB

30days*CABGorPTCA6%) 4/121(3.UFHvs 55/698(7.3-12monthfollow-upDeath&MICP1107655-3Aspirin 500mg,100mgbid6%) 4/121(3.5%) 104/1412(7.12,562patients10%6%4%2%08%TENACITY30-DayClinicalOutcomeTirofiban(n=189)Abciximab(n=194)Death/MIUrgentTVRDeathComposite8.86.95.97.78.25.91.00MI0.51.6P=0.502P=0.499P=0.365P=0.466P=0.361ConclusionsMuchremainstobelearnedabouttheoptimalmedicaltherapyforACSptsThedatafavoraninvasivestrategy,andsuggestdifferentmedicationsanddosesoughtbeadministeredifpursuinganinvasivevs.non-invasivestrategy,andinhighvs.lowriskptsBaselineCharacteristicsNSTEACSPatients:

RecentRCTsandLargeRegistry

Q22003

PURSUIT

CURE

GUSTO-IVACS CRUSADE

Characteristic

(n=9,461) (n=12,562) (n=7,800)(n=5,426)Meanage±SD(yrs) 63±11 63±12 65±11 67±14Diabetesmellitus(%) 23 23 22 33PriorCHF(%) 11 8 8 19PriorPCI(%) 13 --- 10 22PriorCABG(%) 12 18* 8 20NEJM1998;339:436;NEJM2001;345:494;Lancet2001;357:1915-24*CABGorPTCACURECP999547-2YusufSetalNEJM2001;16:494-502Non-STelevationACS12,562patientsASA75to325mgpoqdplacebon=6,3033-12monthfollow-up(average9mo)ASA+clopidogrel(300mgload,75mgqd)n=6,259CURE:AspirinDoseandOutcome

%(N=1,927)(N=7,428)(N=3,201)

ASA/ClopidogrelASA/Placebo

CVDeath,MI,Stroke

MajorBleedingCUREEvent

rate

(%)RR0.80P=0.00005CP995058-6CVdeath,

MI,strokeClopidogrel(n=6,259)Placebo(n=6,303)AspirinandCV

deathMIStrokeNon-CV

deathRR0.92P=NSRR0.77P<0.001RR0.85P=NSRR0.96P=NSACC/AHAACSGuidelineUpdateClassIASAandclopidogrelfor9monthsafterNSTEACS(levelofevidence:B)Class3Donotadministerclopidogrelinthe5daysbeforeCABG BraunwaldE,etal.Heparin(UForLMW)inACSWithoutST

DeathorMI

UFHorLMWH

Control

OR 95%CITheroux 2/122(1.6%) 4/121(3.3%) 0.50 0.10-2.53Cohen 0/37 1/32(3.1%) 0.12 0.01-5.89RISC 3/210(1.4%) 7/189(3.7%) 0.40 0.11-1.39Cohen 4/105(3.8%) 9/109(8.2%) 0.46 0.15-1.41Holdright* 42/154(27.3%) 40/131(30.5%) 0.85 0.51-1.43Gurfinkel 4/70(5.7%) 7/73(9.6%) 0.58 0.17-1.98

(UFH)Gurfinkel 0/68 7/73(9.6%) 0.13 0.03-0.60

(LMWH)FRISC 4/70(5.7%) 36/757(4.8%)