资源描述
Click to edit Master title style,Click to edit Master text styles kbb,Second level,Third level,Fourth level,Fifth level,Combination Lytic Therapy inAcute Myocardial Infarction,C.Michael Gibson,M.D.,Combination Lytic Therapy inA,Pathophysiology of Combination Therapy in AMI,*Gibson et al.,J Am Coll Cardiol.,1995;25:582-589.,Gibson et al.,Circulation.,2001;103:2550-2554.,Combination Therapy,Thrombus,%Stenosis,Minimum Diameter,Epicardial Flow,Myocardial Blush,ST Resolution,Myocardial Flow,Facilitates PCI,Reduces Reinfarction*,Pathophysiology of Combination,Recent Clinical Trials,Unfractionated heparin,Enoxaparin,Unfractionated heparin,Enoxaparin,Abciximab,Abciximab,None,None,ENTIRE,ACC/AHA heparin dose,Low-dose heparin,Enoxaparin,None,Abciximab,None,ASSENT-3,Standard-dose heparin,Low-dose heparin,None,Abciximab,50%TNK-tPA,50%TNK-tPA,100%TNK-tPA,100%TNK-tPA,100%TNK-tPA,50%TNK-tPA,100%TNK-tPA,100%r-PA,50%r-PA,GUSTO-V,Anticoagulant,GP IIb/IIIa,Receptor Inhibitor,Lytic,Trial,Recent Clinical TrialsUnfracti,Clinical Trials:Ongoing,Low-dose heparin,Low-dose heparin,Low-dose heparin,Eptifibatide,Eptifibatide,Eptifibatide,50%TNK-tPA,75%TNK-tPA,100%TNK-tPA,INTEGRITI,Low-dose heparin,Low-dose heparin,Low-dose heparin,Tirofiban,Tirofiban,Tirofiban,50%TNK-tPA,75%TNK-tPA,100%TNK-tPA,FASTER,Anticoagulant,GP IIb/IIIa,Receptor Inhibitor,Lytic,Trial,Clinical Trials:OngoingLow-do,54%,32%,GUSTO-I:A 20%Increase in TIMI Grade 3 Flow is Needed to Yield a 1%Mortality Reduction,The GUSTO Angiographic Investigators.,N Engl J Med.,1993;329:1615-1622.,0,30,50,60,40,20,%TIMI Grade 3 Flow,t-PA,SK,10,t-PA,5,7.4%,6.3%,SK,8,7,6,54%32%GUSTO-I:A 20%Increase,TIMI Grade 3 Flow Pooled Data From Dose Confirmation Phases of Recent Trials,0,40,80,100,60,20,%Patients With TIMI Grade 3 Flow,GUSTO-I,90 min,T14 t-PA,90 min,T14 r-PA,90 min,SPEED,60-90 min,INTRO-AMI,60 min,Pooled,60-90 min,54,73,70,47,40,56,78,73,54,56,64,292,63,87,98,81,329,58,88,100,75,321,Lytic alone,Combination,TIMI Grade 3 Flow Pooled Dat,SPEED:Results of Dose-Confirmation Phase,There was a 7.4%improvement in the rate of TIMI Grade 3 flow,If a 20%improvement is required to improve mortality by 1%,then a 7.4%improvement would be predicted to improve mortality by 0.3%,The SPEED Study Group.,Circulation.,2000;101:2788-2794.,0,40,80,100,r-PA 10+10 U,r-PA 5+5 U+Abx,60,20,Patency(%),TIMI-2,TIMI-3,n=109,n=115,21.6,54.9,47.5,28.7,SPEED:Results of Dose-Confirm,GUSTO-V:Study Design,The GUSTO-V Investigators.,Lancet.,2001;357:1905-1914.,ST,lytic eligible,6 h(n=16,588),ASA,No Abciximab,2 x 10 U bolus(30),Full-dose r-PA,Abciximab,Low-dose Heparin:,60 U/kg bolus followed by 7 U/kg/h infusion,1 end point:mortality at 30 days,2 end point:clinical and safety events at 30 days,2 x 5 U bolus(30),Half-dose r-PA,Standard Heparin:,5000 U bolus followed by800 U/h(80 kg)or 1000 U/h(,80 kg)infusion,GUSTO-V:Study DesignThe GUSTO,Primary End Point:30-Day Mortality,The GUSTO-V Investigators.,Lancet.,2001;357:1905-1914.,0,%Mortality,Days,0,5,10,15,20,25,30,P,=.43 for superiority,Non-Inferiority RR 0.95,(95%CI,0.84-1.08),Std.Reteplase(n=8260),Abx+,Dose Reteplase,(n=8328),4,6,2,5.9%,5.6%,Primary End Point:30-Day Mort,GUSTO-V:Noninferiority Analysis,Adapted with permission from the GUSTO-V Investigators.,Lancet.,2001;357:1905-1914.,Non-Inferiority RR 0.95(95%CI,0.84-1.08),1.11,OR and 95%CI,0.0,2.0,1.0,Abciximab+,Half-dose r-PA superior,Full-dose r-PA,superior,Upper Boundary of 95%CI for Noninferiority,GUSTO-V:Noninferiority Analys,A Comparison of the Outcomes With r-PA Monotherapy in GUSTO-III vs GUSTO-V Trials,The GUSTO-III Investigators.,N Engl J Med.,1997;337:1118-1123.,The GUSTO-V Investigators.,Lancet.,2001;357:1905-1914.,0,3,7,8,5,1,2,6,4,GUSTO III,GUSTO V,7.4%,5.9%,10,138,8,260,Death,P,.001,0,40,50,20,30,10,GUSTO III,GUSTO V,48%,37%,10,138,8,260,Anterior MI,0,0.5,0.9,1.0,0.7,0.3,0.4,0.8,0.6,0.2,GUSTO III,GUSTO V,0.91%,0.59%,10,138,8,260,ICH,P,=.015,0.1,A Comparison of the Outcomes W,0.2,1.2,1.7,2.3,GUSTO-V:Causes of Reinfarction,*Unblinded,unadjudicated,The GUSTO-V Investigators.,Lancet.,2001;357:1905-1914.,0,1,3,4,2,Myocardial Infarction(%),Any,Q-wave,Enzymatic,Ischemic ST,Change*,3.5,0.5,1.6,2.7,r-PA,r-PA+Abx,P,70 yrs,75 yrs,75 yrs,0.4,1.2,0.5,1.1,1.5,0.4,2.1,r-PA(n=8260),r-PA+Abx(n=8328),0.3,P,=.66,P,=.53,P,=.27*,P=,.069*,12/1088,24/1149,28/7179,37/7172,25/2030,31/2135,21/6193,24/6230,ICH by Age Group*Significant t,*,*,*,*,GUSTO-V:PCI Within 6 Hours(Urgent)and Through Day 7,*,P,.0001.,The GUSTO-V Investigators.,Lancet.,2001;357:1905-1914.,5.6,25.4,27.9,8.6,0,15,25,30,20,10,PCI(%),Urgent,Through Day 7,5,r-PA,r-PA+Abx,*GUSTO-V:PCI Within 6 Hour,2.8,9.0,5.4,GUSTO-V:Event Rates in Those Requiring Urgent PCI,Heartwire News.September 2,2001.GUSTO-V:Combination half-dose fibrinolytic plus IIb/IIIa blocker.An Alternative approach to MI?,6.7,4.8,9.6,0,4,10,12,8,Myocardial Infarction(%),r-PA,r-PA+Abx,n=1173,Death,Repeat MI,Death Plus Repeat MI,2,6,2.89.05.4GUSTO-V:Event Rates,GUSTO-V:Conclusions,Compared with r-PA m
展开阅读全文