《SYNERGY研究》PPT课件教案

AddtheauthorandtheaccompanyingtitleSYNERGY研究KennethW.Mahaffey,M.D.JamesJ.Ferguson,M.D.OnbehalfoftheSYNERGYInvestigatorsTheSYNERGYTrialSuperiorYieldoftheNewstrategyofEnoxaparin,Revascularization&GlYcoproteinIIb/IIIaInhibitorsTheSYNERGYTrialKeyPriorTrialsESSENCE/TIMI11b:SuperiorityofenoxaparinvsUFHinconservativemanagementstrategyNICERegistries:ComparablesafetyandefficacytohistoricalcontrolsinPCIACUTE2/INTERACT/AtoZContemporarytrialsinhigherriskpatientsKeyQuestionsWhatistheroleofenoxaparininhigh-riskNSTEMIACSpatientsmanagedwithanearlyinvasivetreatmentstrategy?Canwesafelybringpatientsonenoxaparinrapidlyforwardtothecatheterizationlaboratory?StudyDesignAtleast2of3required:Age60ST(transient)or(+)CK-MBorTroponinEnoxaparinIVHeparinPrimaryendpoint:DeathorMIat30daysHigh-RiskACSPatientsRandomize(n=10,000)EarlyinvasivestrategyOthertherapyperAHA/ACCGuidelines(ASA,-blocker,ACE,clopidogrel,GPIIb/IIIa)60U/kg12U/kg/hr(aPTT50-70sec)1mg/kgSCQ12HStatisticalAssumptionsControlgroup15%death/MI17%reductionprimaryendpointTypeIerrorof5%(2-sided)90%powerSamplesize~10,000patientsSamplesize:800010,000ptsForcrossoverandinterimeventrate1.1zoneofnoninferiorityEurope:5163Australia:253NewZealand:160Brazil:289Argentina:192Canada:1616USA:5702Belgium355Germany456Italy72Poland381Spain412Turkey13912Countries.467Sites.10,027Patients.InclusionCriteriaAge(+)ECG(+)Biomarkers20%16%20%44%EnoxaparinUFH(n=4993)(n=4985)Medianage(years)6868Femalesex(%)3434Hypertension(%)6868Diabetes(%)2930Hypercholesterolemia(%)5859FamilyhistoryofCAD(%)4645Myocardialinfarction(%)2928CHF(%)99Stroke(%)55PVD(%)1010CABG(%)1617PCI(%)2119BaselineCharacteristicsConcomitantMedicationsEnoxaparinUFH(n=4993)(n=4985)Aspirin(%)9595Betablocker(%)8686Aceinhibitor(%)6462Statin(%)6970Clopidogrel(%)6263GPIIb-IIIainhibitor(%)5658Pre-randomizationTherapyEnoxaparinUFHAllPatients(n=4993)(n=4985)(n=9978)Receivedpre-randomization(%):Noantithrombin242524UFHonly293029Enoxaparinonly424243UFHandenoxaparin333EnoxaparinUFH(n=4993)(n=4985)Cathduringbaselinehosp(%)9292Timetocath*2221(hours)(6,44)(6,43)Percutaneousintervention4647TimetoPCI*2322(hours)(6,49)(6,48)CABG(%)1918TimetoCABG*9189(hours)(44,167)(45,166)Dayshospitalized*54(3,8)(3,8)In-hospitalProcedures*Median(25th,75th)KennethW.Mahaffey,M.D.JamesJ.Ferguson,M.D.OnbehalfoftheSYNERGYInvestigatorsTheSYNERGYTrialPrimaryResults(30Days)EnoxaparinUFHUnadjusted(n=4993)(n=4985)P-valueDeathandMI(%)14.014.50.396Death(%)3.23.10.705MI(%)11.712.70.135DeathandMIat30Days0510152025300.80.850.90.951.0FreedomfromDeath/MIDaysfromRandomizationUFHEnoxaparinHR0.96(0.87-1.06)1.1In-hospitalCardiacEventsEnoxaparinUFH(n=4993)(n=4985)CHF(%)8.07.9Cardiogenicshock(%)2.02.3Cardiacarrest(%)2.02.2Ventriculartachycardia/fib(%)4.84.9Atrialfib/flutter(%)8.67.72ndor3rddegreeheartblock(%)1.01.1Acutemitralregurgitation(%)0.30.3Pulmonaryedema(%)0.20.2Deepveinthrombosis(%)0.20.2Ventricularseptaldefect(%)0.1<0.1BleedingEventsEnoxaparinUFH(n=4993)(n=4985)P-valueGUSTOsevere2.92.40.106TIMImajor-clinical:9.17.60.008CABG-related6.85.90.081Non-CABG-related2.41.80.025H/Hdrop-algorithm15.212.50.001AnyRBCtransfusion17.016.00.155ICH<0.1<0.1NSPCIPatients:ThromboticComplicationsEnoxaparinUFH(n=2321)(n=2364)AnyunsuccessfulPCI3.63.4Anythreatenedabruptclosure1.11.0Anyabruptclosure1.31.7EmergencyCABG0.30.3NopriorUFHEnoxBothPre-randomizationNopriorUFHEnoxBothPre-randomizationRandomizationPriorAntithrombinTherapy:EfficacyandSafetyEnoxUFH(%)(%)30-DAYDEATH/MIBLEEDINGGUSTOSevereTIMIMajorEnoxUFH(%)(%)2.92.4Total(n=9978)14.014.59.17.63.11.8NoPriorRx(n=2440)12.614.89.76.93.12.2ConsistentTherapy(n=6138)13.315.99.37.9NopriorUFHEnoxBothPre-randomizationRandomizationNopriorUFHEnoxBothPre-randomizationRandomizationCrossoverCrossovers:RelationtoBleedingTIMIMajorGUSTOSevere(n=9978)(n=9180)(n=798)(n=9978)(n=9180)(n=798)EnoxaparinUFHCrossovers:RelationtoOutcomeEnoxaparinUFHConsistentRxDeath/MITotalPopulationDeath/MI(n=9978)(n=9180)(n=798)(n=6130)(n=5637)(n=493)SystematicOverview:30-DayDeath/MIandIn-hospitalTransfusions30-DAYDEATH/MIIN-HOSPITALTRANSFUSIONSEnoxUFH2.6%3.3%0.7%0.6%2.5%4.3%1.0%0.8%17.0%16.0%0.8%0.9%ESSENCEINTERACTTIMI11BACUTE2AtoZSYNERGYEnoxUFH5.0%9.0%7.4%8.3%7.9%8.1%7.4%7.9%14.0%14.5%6.2%7.7%SystematicOverview:Death/MIandBleeding10.1%11.0%EnoxUFH8.2%7.8%4.8%4.1%(n=21,946)(n=22,104)(n=22,104)AtoZdidnotincludeCABGdata.SystematicOverview—NoPre-randoTherapy:Death/MIandBleeding8.1%9.5%EnoxUFH5.6%5.5%3.5%2.7%(n=9835)(n=8627)(n=8627)AtoZdidnotincludeCABGdata.SummaryHigh-riskpopulationtreatedwithanearlyinvasivemanagementstrategyThestudySummaryEfficacy—notsuperiorbutatleastaseffectiveasUFHintheoverallpopulationTheresultsmetcriteriafornon-inferiorityHigh-riskpopulationtreatedwithanearlyinvasivemanagementstrategySummaryEfficacy—notsuperiorbutatleastaseffectiveasUFHintheoverallpopulationBleeding—morefrequentwithenoxaparinTheresultsUFHEnoxaparin7.6%9.1%2.4%2.9%16.0%17.0%TIMIMajorGUSTOSevereTransfusionHigh-riskpopulationtreatedwithanearlyinvasivemanagementstrategyp=0.007p=0.106p=0.155SummaryPriorantithrombotictherapyPost-randomizationmanagementBleedingdefinitionsAge,renalfunctionIssuestoconsiderSummaryAnoverviewofallrecentRCTscomparingenoxaparinandUFHshowsaconsistenteffectacrossthemanagementspectrumThestudyincontextPriorantithrombotictherapyPost-randomizationmanagementBleedingdefinitionsAge,renalfunctionAddtheauthorandtheaccompanyingtitle生活图标元素商务图标元素商务图标元素商务图标元素商务图标元素