不稳定型心绞痛和非段抬高心梗的治疗.ppt

Acute Coronary Syndromes:Management of UA/NSTEMIOverview of 2003 Updates to the Overview of 2003 Updates to the ACC/AHA Guideline for UA/NSTEMIACC/AHA Guideline for UA/NSTEMIAssess likelihood of CADRisk stratificationTarget therapy:more aggressive treatment in higher-risk patientsAnti-ischemic,antithrombotic therapyInvasive vs conservative strategyDischarge planning(risk factor modification and long-term medical therapy)ACC/AHA,American College of Cardiology/American Heart Association;UA,unstable angina;NSTEMI,nonST-segment elevation myocardial infarction.Braunwald E,et al.J Am Col.Cardiol.2000;36:970-1062.Acute Management of UA/NSTEMIAcute Management of UA/NSTEMIAnti-Ischemic TherapyAnti-Ischemic TherapyOxygen,bed rest,ECG monitoringOxygen,bed rest,ECG monitoringNitroglycerinNitroglycerin-BlockersBlockersACE inhibitorsACE inhibitorsUA,unstable angina;NSTEMI,non-ST-segment elevation myocardial infarction;ECG,electrocardiogram;ACE,angiotensin-converting enzyme.Braunwald E,et al.J Am Coll Cardiol.2000;36:970-1062.Antithrombotic TherapyAntithrombotic TherapyAntiplatelet therapyAntiplatelet therapyAnticoagulant therapyAnticoagulant therapyPossible Possible ACSACSAspirinAspirinAspirinAspirin+IV HeparinIV Heparin+IV Platelet IV Platelet GP IIb/IIIa GP IIb/IIIa AntagonistAntagonistDefinite ACS With Definite ACS With Invasive Strategy Invasive Strategy(Catheterization/PCI)(Catheterization/PCI)or High Risk(IIa)*or High Risk(IIa)*ClopidogrelClopidogrelAspirinAspirin+SQ LMWH*SQ LMWH*ororIV HeparinIV HeparinLikely/Definite Likely/Definite ACSACSClopidogrelClopidogrel*Class IIa:enoxaparin preferred over UFH unless CABG planned within 24 hours.ACC,American College of Cardiology;AHA,American Heart association;ACS,acute coronary syndrome;PCI,percutaneous coronary intervention;SQLMWH,subcutaneous low molecular-weight heparin;IV,intravenous.Braunwald E,et al.J Am Coll Cardiol.2000;36:970-1062.ACC/AHA Class I Recommendations for ACC/AHA Class I Recommendations for Antithrombotic Therapy*Antithrombotic Therapy*17.117.16.5*6.5*PlaceboPlaceboASAASA0 05 5101015152020Patients(%)Patients()Unstable AnginaUnstable Angina 25.025.011.0*11.0*ASAASA0 01010202030303.33.31.9*1.9*ASAASA0 01 12 23 34 411.811.89.4*9.4*ASAASA0 05 510101515Acute MIAcute MIAspirin in Acute Coronary SyndromesAspirin in Acute Coronary Syndromes*P P.0001.0001Death or MIDeath or MI*P P=.003=.003ReocclusionReocclusion*P P=.012=.012MIMI*P P.001.001DeathDeathN=3973995134198587860085878600MI,myocardial infarction;ASA,acetylsalicylic acid;RISC,Research on InStability in Coronary artery disease.RISC Group.Lancet.1990;336:827-830.Roux S,et al.J Am Coll Cardiol.1992;19:671-677.ISIS-2.Lancet.1988;2:349-360.PlaceboPlaceboPlaceboPlaceboPlaceboPlaceboAspirin in Acute Coronary SyndromesAspirin in Acute Coronary Syndromes12.912.93.9*3.9*ASAASA0 05 51010151511.911.93.3*3.3*ASAASA0 05 51010151512.912.96.2*6.2*ASAASA0 05 5101015152.22.21.3*1.3*ASAASA0 00.50.51 11.51.52 22.52.5UA/NSTEMIUA/NSTEMIPrimary Primary PreventionPreventionStable Stable AnginaAngina*P P.0001.0001MIMI*P P=.0003=.0003MIMI*P P=.008=.008Death or MIDeath or MI*P P=.012=.012Death or MIDeath or MIN=1103411037155178279276118121MI,myocardial infarction;ASA,acetylsalicylic acid;RISC,Research on InStability in Coronary artery disease;ISIS-2,Second International Study of Infarct Survival.PHS.N Engl J Med.1989;321:129-35.Ridker PM,et al.AJC.1991;114:835-839.Cairns JA,et al.N Engl J Med.1985;313:1369-1375.Theroux P,et al.N Engl J Med.1988;319:1105-1111.PlaceboPlaceboPlaceboPlaceboPlaceboPlaceboPlaceboPlaceboPatients(%)Patients(%)Indirect Comparisons of ASA Doses on Indirect Comparisons of ASA Doses on Vascular Events in High-Risk PatientsVascular Events in High-Risk Patients*Odds reduction.Treatment effect P.0001.ASA,acetylsalicylic acid.Adapted with permission from BMJ Publishing Group.Antithrombotic Trialists Collaboration.BMJ.2002;324:71-86.0.50.51.01.01.51.52.02.0500-1500 mg500-1500 mg3434 19 19160-325 mg160-325 mg1919 26 2675-150 mg75-150 mg1212 32 3275 mg162 mg/d162 mg/d(n=2179)(n=2179)Primary end pointPrimary end point16.416.418.618.6Death,MI,strokeDeath,MI,stroke6.26.26.16.1DeathDeath2.82.81.71.7MIMI2.02.02.12.1StrokeStroke2.12.1282.8Urgent hospital careUrgent hospital care9.59.510.610.6Urgent resuscitationUrgent resuscitation7.37.310.010.0Internal bleedingInternal bleeding2.42.43.33.3Any bleedingAny bleeding11.111.115.415.4TransfusionTransfusion1.01.02.02.0ClopidogrelClopidogrel+ASA+ASA(N=6259)(N=6259)PlaceboPlacebo+ASA+ASA*(N=6303)(N=6303)CURE:Major Bleeding at 1 year by ASA DoseCURE:Major Bleeding at 1 year by ASA Dose 200 mg(N=4110)3.7%4.9%P value for trend.0001.0009*P=.0001.P=.0009.Adapted from Peters RJG,et al.Circulation.2003;108:1682-1687.ASA DoseASA DoseRR:RR:Death/MIDeath/MIASA Alone ASA Alone 68/655=10.4%68/655=10.4%Heparin+ASA Heparin+ASA 55/698=7.9%55/698=7.9%B BB BB BB BB BB BB B0.10.11 11010Summary Relative RiskSummary Relative Risk0.67(0.44-0.1.02)0.67(0.44-0.1.02)TherouxTherouxRISCRISCCohen 1990Cohen 1990ATACSATACSHoldrightHoldrightGurfinkelGurfinkelComparison of Heparin+ASA vs ASA AloneComparison of Heparin+ASA vs ASA AloneASA,acetylsalicylic acid;RISC,Research on InStability in Coronary artery disease;ATACS,Antithrombotic Therapy in Acute Company Syndromes;RR,relative risk;MI,myocardial infarction.Oler A,et al.JAMA.1996;276:811-815.(with permission)TIMI,Thrombosis in Myocardial Infarction;ESSENCE,Efficacy and Safety of Subcutaneous Enozapam in NonQ-Wave Coronary Events;UHF,unfractionated heparin;ENOX,enoxaparin;MI,myocardial infarction;OR,odds ratio.Antman EM,et al.Circulation.1999;100:1602-1608.(with permission)TIMI TIMI IIIIB/ESSENCE Metanalysis:B/ESSENCE Metanalysis:Enoxaparin vs Unfractionated HeparinEnoxaparin vs Unfractionated Heparin8.6 7.1 0.82(0.69-0.97)18 .026.5 5.2 0.79(0.65-0.96)21 .025.3 4.1 0.77(0.62-0.95)23 .021.81.4 0.80(0.55-1.16)20 .24 0.512Day281443UFH(%)ENOX(%)OR(95 CI)Favors ENOXFavors UFHPORDeath or MI%0123456789081624324048566472Patients(%)Hours from Randomization7.3%5.5%RRR 24%P=.026UFH(n=1957)ENOX(n=1953)UHF,unfractionated heparin;ENOX,enoxaparin;RRR,relative risk ratio.Antman EM.Circulation.1999;100:1593-1601.(with permission)TIMI TIMI IIIIB:Early Phase B:Early Phase Death/MI/Urgent RevascDeath/MI/Urgent Revasc0123456789081624324048566472Patients(%)Hours from Randomization7.3%5.5%RRR 24%P=.026UFH(n=1957)ENOX(n=1953)UFHUFHEnoxaparinEnoxaparinP PP P=.03=.03=.03=.03Major Bleeds96 HoursMajor Bleeds96 HoursMajor Bleeds96 HoursMajor Bleeds96 HoursINTERACT:Enoxaparin vs Unfractionated INTERACT:Enoxaparin vs Unfractionated Heparin With GP IIb/IIIa InhibitorsHeparin With GP IIb/IIIa InhibitorsGoodman SG,et al.Circulation.2003;107:238-244.Death/MI30 DaysDeath/MI30 DaysDeath/MI30 DaysDeath/MI30 DaysP PP P=.031=.031=.031=.031UFHUFHEnoxaparinEnoxaparinPercentPercentA-Phase Study DesignA-Phase Study DesignUA/UA/NSTEMINSTEMIFinal A Final A visit 30 visit 30 days days RandomizeRandomize-24-24 hourshours Chest painChest pain Min 0 hourMin 0 hourMax 120 hourMax 120 hourTirofiban Tirofiban+ASA+ASA Hour 0Hour 0Aggressive or conservativeAggressive or conservativecare per local practicecare per local practice2026202619611961ENOXENOX1mg/kg q12 hr1mg/kg q12 hrUFHUFHWeight-adjustedWeight-adjustedZ ZZ Z Treat&Evaluate Treat&Evaluate for Z-Phasefor Z-Phase2018201819521952398739871 1 endpoint endpoint 7 days7 daysBlazing M.presented at ACC 2003.0 01010202030300 02 24 46 68 810101212UFHUFHEnoxaparinEnoxaparinUFHUFHENOXENOXDays From RandomizationDays From RandomizationEvent Rates(%)Event Rates(%)Day 7Day 78.4%(169 events)8.4%(169 events)9.4%(184 events)9.4%(184 events)7-and 30-Day Primary Endpoint7-and 30-Day Primary EndpointComposite Death,MI and Refractory IschemiaComposite Death,MI and Refractory IschemiaComposite Death,MI and Refractory IschemiaComposite Death,MI and Refractory IschemiaBlazing M.presented ACC 2003.Enox Test vs OutcomesEnox Test vs OutcomesMoliterno DJ,et al.JACC.2003;42:1132-1139.(with permission)Death/MI/Urg TVRDeath/MI/Urg TVRBleedingBleeding303025252020151510105 50 0200200 250250 300300 350350 400400 450450 500500 550550 600600200200 250250 300300 350350 400400 450450 500500 550550 600600Probability of MACE(%)Probability of MACE(%)Probability of Any Bleeding(%)Probability of Any Bleeding(%)303025252020151510105 50 0ENOX Time(sec)ENOX Time(sec)ENOX Time(sec)ENOX Time(sec)Direct Thrombin Inhibitor Trialists Direct Thrombin Inhibitor Trialists CollaborationCollaborationDirect Thrombin Inhibitor Trialists Collaborative Group.Lancet.2002;359:294-302.(with permission)11 RCTS11 RCTS36,000 Pts36,000 PtsACS,PCI ACS,PCI Death orDeath orMyocardialMyocardialInfarctionInfarctionDirect ThrombinDirect ThrombinInhibitorInhibitorHeparinHeparin(N=18,736)(N=18,736)(N=17,184)(N=17,184)OROR(95%Cl)(95%Cl)End of treatment7 days30 daysEnd of treatment7 days3 daysDeathDeathMyocardialMyocardialInfarctionInfarctionEnd of treatment7 days30 daysEnd of treatment7 days30 daysStrokeStrokeMajor bleedingMajor bleedingduring treatmentduring treatmentIntracranial Intracranial bleeding during bleeding during treatmenttreatment815(4.3%)883(5.1%)947(5.0%)990(5.8%)1399(7.4%)1409(8.2%)355(1.9%)346(2.0%)422(2.2%)395(2.3%)685(3.6%)642(3.7%)522(2.8%)596(3.5%)601(3.2%)672(3.9%)876(4.7%)917(5.3%)62(0.33%)60(0.35%)72(0.38%)70(0.41%)120(064%)110(0.64%)360(1.90%)403(2.30%)21(0.11%)28(0.16%)0.01.02.0Direct ThrombinInhibitorHeparin Better0.85(0.77-0.94%)0.88(0.80-0.96%)0.91(0.84-0.99%)0.97(0.83-1.13%)1.00(0.87-1.16%)1.01(0.90-1.12%)0.80(0.71-0.90%)0.81(0.72-0.91%)0.87(0.79-0.95%)0.95(0.66-1.35%)0.94(0.68-1.31%)1.01(0.78-1.31%)0.75(0.65-0.87%)0.72(0.42-1.23%)Early invasive strategyEarly invasive strategy+/-GP IIb/IIIa+/-GP IIb/IIIa Catheterization within Catheterization within 8 hours of last 8 hours of last subcutaneous dosesubcutaneous doseUA/NSTEMIUA/NSTEMIIdentified,LMWHIdentified,LMWH-GP IIb/IIIa-GP IIb/IIIa+GP IIb/IIIa+GP IIb/IIIa Catheterization between 8-12 hours Catheterization between 8-12 hours of last subcutaneous doseof last subcutaneous doseNo No additionaladditionalUFH or UFH or LMWHLMWHAdditionalAdditionalEnoxaparinEnoxaparin0.3 mg/kg IV 0.3 mg/kg IV bolusbolusSupplementSupplementwith UFH with UFH 5050U/kg,aim forU/kg,aim forACT 200-250ACT 200-250SupplementSupplementwith UFH with UFH 0.1 0.1 g/Lg/LCAPTUREPRISM14.810.27.59.105101520TnI 0.1 g/LP0.1P.0014.919.65.25.80510152025HeparinTirofibanHeparinAbciximab+HeparinDeath or MI at 30 days(%)Death or MI at 30 days(%)GP IIb/IIIa Inhibition in TnI+Patients GP IIb/IIIa Inhibition in TnI+Patients by Revascularization:PRISM Studyby Revascularization:PRISM StudyTnI,troponin I;PRISM,Platelet Receptor Inhibition for Ischemic Syndrome Management study;MI,myocardial infarction.Heeschen C,et al.Lancet.1999;354:1757-1762.(with permission)Death/MI at 30 DaysDeath/MI at 30 Days0.37(0.15-0.93)0.37(0.15-0.93)P P =.02=.020.30(0.10-0.84)0.30(0.10-0.84)P P =.004=.004161612128 84 40 00 05 510101515202025253030Event rate(%)Event rate(%)Follow-up(days)Follow-up(days)No revascularizationNo revascularizationRevascularizationRevascularizationHeparinHeparinHeparinHeparinTirofiban Tirofiban TirofibanTirofibanGP IIb/IIIa Inhibition in DiabeticsGP IIb/IIIa Inhibition in DiabeticsRoffi M,et al.Circulation.2001;104:2767-2771.(with permission)30-Day Mortality in Diabetic Patients30-Day Mortality in Diabetic Patients2163687362167741211576458PURSUITPRISMPRISM-PLUSGUSTO IVPARAGON APARAGON BPooled6.1%4.2%6.7%7.8%6.2%4.8%6.2%5.1%1.8%3.6%5.0%4.6%4.9%4.6%P=.33P=.07P=.17P=.022P=.51P=.93P=.007TrialTrialN NOdds Ratio&95%ClOdds Ratio&95%ClPlaceboPlaceboIIb/IIIaIIb/IIIaBreslow-Day:P=.50IIb/IIIa BetterPlacebo BetterOR=0.74OR=0.7400.511.52Intravenous GP IIb/IIIa Antagonists in ACS:Intravenous GP IIb/IIIa Antagonists in ACS:Death or MI(at 30 Days)in PCI/CABG 5 Days Death or MI(at 30 Days)in PCI/CABG 5 Days Cohort and in Medical Treatment CohortCohort and in Medical Treatment Cohort17.317.310.510.514.314.310.110.10 02 24 46 68 8101012121414161618182020InterventionInterventionMedical TreatmentMedical TreatmentDeath or MIDeath or MIPlaceboPlaceboIV GP IIb/IIIaIV GP IIb/IIIaP P=.001=.001P P=NS=NS(N=5847)(N=5847)(N=25,555)(N=25,555)ACS,acute coronary syndrome;MI,myocardial infarction;PCI,percutaneous coronary intervention;CABG,coronary artery bypass graft;NS,not significant.Boersma E,et al.Lancet.2002;359:189-198.Interaction Interaction P P.02.02GP Iib/IIIa Inhibitor NSTE ACS Trials Analysis GP Iib/IIIa Inhibitor NSTE ACS Trials Analysis Risk-Adjusted Mortality at 30 DaysRisk-Adjusted Mortality at 30 DaysPeterson ED,et al.J Am Coll Cardiol.2003;42:45-53.Boersma E,et al.Lancet.2002;359:189-198.0.50.52.02.01.01.0NRMINRMI1 1BoersmaBoersma2 20.83-1.010.83-1.010.910.910.79-0.970.79-0.970.880.8895%CI95%CIOdds RatioOdds RatioOdds Ratio for Mortality at 30 Odds Ratio for Mortality at 30 DaysDaysGP IIb/IIIa Inhibitor GP IIb/IIIa Inhibitor FavoredFavored(aspirin (aspirinheparin)heparin)Control ArmControl Arm Favored Favored(aspirin (aspirin+heparin)heparin)Mortality by Hospitals Use of Early Mortality by Hospitals Use of Early GP IIb/IIIa Inhibitors(N=1189 GP IIb/IIIa Inhibitors(N=1189 Hospitals)Hospitals)Hospital Use of Early GP IIb/IIIa inhibitors in NRMI(%)Hospital Use of Early GP IIb/IIIa inhibitors in NRMI(%)In-Hospital Mortality In-Hospital Mortality(%)(%)530301414121210108 86 64 42 20 0NRMI,National Registry of Myocardial Infarction.Peterson ED,et al.J Am Coll Cardiol.2003;42:45-53.(with permission)In-Hospital Mortality In-Hospital Mortality(%)(%)Efficacy of Clopidogrel or Ticlopidine Efficacy of Clopidogrel or Ticlopidine in Reducing Coronary Events After in Reducing Coronary Events After StentingStentingCLASSICS,Clopidogrel Aspirin Stent Intervention Coopoerative Study.Bhatt DL,et al.J Am Coll Cardiol.2002;39:9-14.(with permission)30-Day Major Adverse Cardiac Events30-Day Major Adverse Cardiac EventsOdds Ratio&95%CIOdds Ratio&95%CITiclopidine Ticlopidine BetterBetterClopidogrel Clopidogrel BetterBetterTrialTrialClopid.(%)Clopid.(%)Ticl.(%)Ticl.(%)N NOverallOverall13,95513,9552.02.03.93.90.10.11 11010TOPPSCLASSICS101610202.61.33.50.9Lenox HillCCF256523692.45.73.88.9Mller7003.11.7Wessex-361-3613.45.2N.Memorial13780.82.2S.Illinois8752.11.4Wash.Hosp.8442.00.5Mayo28270.61.6OR=.73,OR=.73,P P=.003=.003THANK YOUSUCCESS2024/5/27 周一29.CURE,Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events;MI,myocardial infarction;CV,cardiovascular;RRR,relative risk reduction.Plavix package insert;2002.Adapted with permission(2002)from the Massachusetts Medical Society.Yusuf S,et al.N Engl J Med.2001;345:494-502.0.000.020.040.060.080.100.120.14Cumulative Hazard RateClopidogrel+Aspirin369Placebo+AspirinFollow-up(mo)P=.00009(N=12,562)01220%RRRCURE:Primary End Point CURE:Primary End Point MI/Stroke/CV DeathMI/Stroke/CV DeathCURE:MI/Stroke/CV Death/Severe CURE:MI/Stroke/CV Death/Severe Ischemia Within 24 Hours of RandomizationIschemia Within 24 Hours of RandomizationCURE,Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Ev