急性心肌梗死的紧急干预.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Acute Myocardial Infarction(AMI):The Urgent Intervention,AMI Disease State,AMI occurs when an artery supplying the heart muscle becomes occluded,Occlusion is usually caused by atherosclerosis accompanied by acute thrombus formation,Atherosclerotic plaques inside the arterial wall can rupture,triggering the formation of the thrombus,If a thrombus grows large enough,it can occlude the blood vessel completely,causing ischemia in the heart muscle,Prolonged ischemia can lead to infarction,reducing the power of the heart to pump oxygenated blood around the body,and potentially leading to heart failure and death,Risk factors for AMI include hypercholesterolemia,diabetes,hypertension,smoking,previous history of coronary artery disease(CAD),family history of CAD,and metabolic syndrome.,www.nlm.nih.gov/medlineplus/ency/imagepages/17004.htm,AMI Disease State,An atherosclerotic plaque is shown obstructing a coronary artery,AMI Disease State,In AMI,plaque spontaneously ruptures within the vessel.Platelets become activated,triggering the formation of thrombus,AMI Disease State,Thrombus present in the vessel is shown in this angiogram,AMI Disease State,Clumps of activated platelets can break off and travel downstream,blocking the microvessels and preventing blood from reaching the heart muscle,AMI Diagnosis,STEMI(ST-segment elevation MI),Ischemic symptoms lasting 30 mins(chest pain,dyspnea,etc.),On electrocardiogram(EKG),ST-segment elevation of,1 mm in,at least two contiguous leads,Confirmatory Evidence,Elevation in creatine kinase to at least three times the upper limit of normal with a concomitant rise in MB isoenzyme,Elevation in troponin levels,New Q wave on ECG,Coronary artery occlusion with angiographic appearance of thrombus,www.nlm.nih.gov/medlineplus/ency/imagepages/17004.htm,Abciximab Indication,Abciximab is indicated as an adjunct to percutaneous coronary intervention(PCI)for the prevention of cardiac ischemic complications:,In patients undergoing PCI,In patients with unstable angina(UA)not responding to conventional medical therapy when PCI is planned within 24 hours.,Safety and efficacy of abciximab use in patients not undergoing PCI have not been established.Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.,Clinical Studies of AMI and Abciximab,Abciximab has been studied in the following trials outlined in this presentation:,RAPPORT,1,Neumann et al.,2,ISAR-2,3,ADMIRAL,4,CADILLAC,5,6,ACE,7,1.Brener SJ et al.,Circulation,1998;,98,:73441.2.Neumann F-J et al.,Circulation,1998;,98,:2695701.,3.Neumann F-J et al.,J Am Coll Cardiology,2000;,35,:91521.4.Montalescot G et al.,N Eng J Med,2001;,344:,1895903.,5.Tcheng JE et al.,Circulation,2003;,108,:131623.6.Stone GW et al.,N Engl J Med,2002;,346,:95766.,7.Antoniucci D et al.,J Am Coll Cardiol,2003;,42,:187985.,PCI with Abciximab for AMI,Data from the studies outlined in this presentation will illustrate the effect that primary PCI with abciximab for AMI patients has on:,Clinical outcomes,1,Microvascular perfusion,2,Left ventricular(LV)function,1,2,Combined with stenting,abciximab initiated before catheterization improved the composite of death,reinfarction,or target vessel revascularization(TVR)in patients with AMI,as compared with placebo at 30 days,1,1.Montalescot G,Barragan P,Wittenberg O et al.,N Engl J Med,2001;,344,:1895903.,2.Neumann F-J,Blasini R,Schmitt C et al.,Circulation,1998;,98,:2695701.,Abciximab Administration,Abciximab(represented as the teal green cloud,entering the vessel)is shown flowing through a,heavily artherosclerosed vessel,PCI,Intervention with a balloon and stent results in the flattening and cracking of plaque,and the dislodging of sections of the plaque,Abciximab and PCI,Abciximab prevents the thrombus formation that the intervention triggers.Blood flows freely and the PCI may proceed smoothly,RAPPORT Study,First dedicated randomized trial of platelet GPIIb/IIIa inhibition in AMI patients during percutaneous transluminal coronary angioplasty(PTCA),Patients with acute MI(within 12 hours)undergoing PTCA were randomized to placebo or abciximab,The primary efficacy endpoint was death,MI,or any TVR at 6 months by intent-to-treat(ITT)analysis,Brener,SJ et al.,Circulation,1998;,98,:73441.,RAPPORT:Trial Design,*0.25 mg/kg bolus followed by a 0.125,g/kg/min(max.10 g/min)for 12 h,*,100 U/kg bolus followed by additional weight-adjusted doses(maintain an activated clotting time ACT 300 seconds during procedure).Heparin infusion could be continued for a maximum of 48 h to maintain partial thromboplastin time(PTT)6085 seconds,Heparin*,Abciximab*(n=241),Placebo*(n=242),Aspirin,Actual treatment(AT)analysis(n=409),ITT analysis(n=483),ST,AMI 12 h,Randomize,1 endpoint:death,recurrent MI or any TVR at 6 months by ITT analysis,2 endpoint:death,recurrent MI,or urgent TVR at 7 and 30 days,Brener,SJ et al.,Circulation,1998;,98,:73441.,RAPPORT:6-Month ITT Outcome,17.8,4.5,7.4,11.2,8.7,4.1,6.6,0,5,10,15,20,25,30,Death,MI,or any,TVR,Death,MI,or urgent,TVR,Death,Repeat MI,Death or,Repeat MI,Urgent,TVR,Incidence (%),p=0.048,RR 35%,p=0.82,p=0.70,p=0.36,p=0.01,p=0.90,28.1,28.2,11.6,8.7,3.3,Placebo(n=242),Abciximab(n=241),Brener,SJ et al.,Circulation,1998;,98,:73441.,Placebo(n=242),Abciximab(n=241),RAPPORT:ITT Analysis,9.9,11.2,17.8,3.3,5.8,11.6,0,5,10,15,20,7-day,30-day,6-month*,Incidence of death,MI,or urgent TVR(%),p=0.003,RR 67%,p=0.048,RR 35%,p=0.03,RR 48%,*6-month composite of death,MI,or,urgent,TVR was not a prespecified secondary endpoint,Brener,SJ et al.,Circulation,1998;,98,:73441.,0,5,10,15,20,7-day,30-day,6-month,Incidence of death,MI,or urgent TVR(%),RAPPORT:Actual Treatment(AT)Analysis,10.5,12.0,19.9,2.8,4.6,10.6,p=0.001,RR 73%,p=0.004,RR 47%,p=0.005,RR 62%,Placebo(n=191),Abciximab(n=218),25,Brener,SJ et al.,Circulation,1998;,98,:73441.,Abciximab(n=241),Placebo(n=242),9.5,0,7.9,16.6,0,13.7,0,2,4,6,8,10,12,14,16,18,TIMI major bleeding,Intracranial,hemorrhage,All transfusions,Incidence(%),p=0.02,p=0.04,RAPPORT:30-Day Safety,p=ns,Brener,SJ et al.,Circulation,1998;,98,:73441.,RAPPORT:Conclusions,Abciximab reduced the major adverse outcomes death,reinfarction,or urgent TVR at 7 days,30 days and extended to 6 months,Abciximab during PTCA did not show a reduction in TVR and,therefore,did not meet its primary endpoint.,As this trial was performed in the mid-1990s,stents were highly discouraged and rarely used in this trial,Brener,SJ et al.,Circulation,1998;,98,:73441.,Neumann Study,Neumann et al.investigated the effect of abciximab on papaverine-induced coronary peak flow velocity and on wall motion in the infarct area within 14 days after successful stent placement in the infarct-related artery,Patients undergoing stenting in AMI(within 48 hours)were randomized to standard-dose heparin or abciximab plus heparin,Prospective randomized trial to investigate microvascular and contractile recovery after revascularization with stent placement and to compare the effect of glycoprotein(GP)IIb/IIIa blockade by abciximab with standard-dose heparin,Neumann F-J et al.,Circulation,1998;,98,:2695701.,Neumann Trial Design,AMI 48 h,Heparin(5000 U)+aspirin(500 mg),Abciximab*(n=102),1 endpoints:differences in papaverine-induced coronary flow velocity and in wall motion index between the initial study and 14-day follow-up,2 endpoint:clinical outcome during 30-day follow-up,*Heparin(10,000 U)followed by heparin(1000 U/h for 12 h after sheath removal),*0.25 mg/kg bolus followed by,10 g/min for 12 h plus heparin(25000 U),Randomize,Ticlopidine(250 mg twice daily for four weeks),Aspirin(100 mg twice daily throughout study),Nitroglycerin(0.2 mg after re-establishing antegrade flow),Usual care*(n=98),Neumann F-J et al.,Circulation,1998;,98,:2695701.,Cardiac Function Parameters at 14 days,0.44,0.15,0,0.2,0.4,0.6,0.8,56,62,0,20,40,60,80,p=0.007,p=0.003,n=79,n=72,n=72,n=79,p=0.024,n=72,n=80,10.4,18.1,0,5,10,15,20,25,peak flow velocity,(cm/s),wall motion index,(SD/Chords),Global LVEF,(%),Usual care Abciximab,Circ,1998;98:2695-701,Neumann et al.,Primary PCI for AMI,Usual care(n=72),Abciximab(n=79),8.3,3.8,0,1,2,3,4,5,6,7,8,9,Blood transfusions,Incidence(%),p=0.32,Neumann:30-Day Safety,Neumann F-J et al.,Circulation,1998;,98,:2695701.,Neumann:Conclusions,Abciximab improved microvascular perfusion and recovery of contractile function,LV function was improved in patients who received abciximab,Neumann F-J et al.,Circulation,1998;,98,:2695701.,ISAR-2 Study,ISAR-2 investigated the effects of abciximab with stenting for AMI,Patients undergoing stenting(48 hours after AMI)were randomized to standard-dose heparin or abciximab plus reduced-dose heparin(open-label),The primary endpoint was angiographic restenosis as defined by late loss at 6 months,Also analyzed clinical outcome by the composite endpoint of death,recurrent nonfatal MI,and target lesion revascularization(TLR),Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,ISAR-2:Trial Design,AMI 48 h,Heparin(5000 U)+aspirin(500 mg),Abciximab*(n=201),Usual care*(n=200),1 endpoint:late loss,2 endpoint:composite of death,recurrent MI,and TLR at 30 days,6 months,and 1 year,*Heparin(10,000 U)followed by heparin(1000 U/h for 12 h after sheath removal),*0.25 mg/kg bolus followed by,10 g/min for 12 h plus heparin(2500 U),Eligible for 6-month angiographic follow-up(n=292/366),Randomize,Ticlopidine(250 mg twice daily for four weeks),Aspirin(100 mg twice daily throughout study),Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,ISAR-2:6-Month Late Loss,p=0.61,1.26,0.85,1.21,0.74,Usual care,(n=144),Abciximab,(n=148),0,0.5,1,1.5,2,2.5,Late loss(mm),Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,Usual Care(n=200),Abciximab(n=201),ISAR-2:30-Day Outcome(Secondary Endpoint),10.5,6.0,4.5,1.5,5.0,5.0,2.5,2.0,0.5,3.0,0,2,4,6,8,10,12,Any cardiac,event,Death or,Repeat MI,Death,Non-fatal MI,TLR,Incidence(%),p=0.038,RR 52%,p=0.08,p=0.16,p=0.62,p=0.30,Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,ISAR-2:1-Year Event-Free Survival,Heparin,Month After Stent Placement,Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,0,50,60,70,80,90,100,Global EF(%),*,Absolute RR in adverse cardiac events,5.7%*,Abciximab,5.5%*,P=0.17,Event-Free Survival(%),0,12,11,10,1,2,3,4,5,6,7,8,9,ISAR-2:30-Day Safety Data,0,3.5,0,4.5,0,0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,Stroke,Blood transfusions,Incidence(%),p=0.79,Usual Care(n=200),Abciximab(n=201),p=ns,Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,ISAR-2:Conclusions,No effect of abciximab on angiographic restenosis at 6 months was measured by late loss,Abciximab significantly reduced the composite of death,reinfarction,or TLR,at 30 days,The results support the adjunctive use of abciximab with stenting in AMI patients,Neumann F-J et al.,J,Am,Coll,Cardiol,2000;,35,:91521.,ADMIRAL Study,A multicenter,double-blind,randomized trial to reflect the common practice of primary stenting in patients with AMI,Patients with AMI were randomized to either abciximab plus stenting or placebo plus stenting before undergoing coronary angiography,The primary endpoint was a composite of death,MI,or urgent TVR at 30 days,Montalescot G et al.,N Eng J Med,2001;,344,:1895903.,ADMIRAL:Trial Design,Four coronary angiograms,Admission,Post-PCI,24 h post-PCI,6 m post-PCI,*0.25 mg/kg bolus followed by a 0.125,g/kg/min(max.10 g/min)for 12 h,*,70 U/kg(max.7000 U)followed by 7 U/kg/h(maintain aPTT between 1.5,2.0 x control value)until the 24 h follow-up angiogram completed,ST,18 years old,First symptoms of AMI within 12 hours before enrollment,ST-segment elevation 1 mm in at least 2 contiguous EKG leads,Patients with small arteries or with cardiogenic shock were not excluded from this trial,Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,ADMIRAL:30-Day Clinical Events,14.6,6.6,2.6,6.6,7.9,20.5,6,1.3,1.3,3.4,4.7,12.1,0,5,10,15,20,25,Death,MI,or urgent,TVR,Death,Repeat MI,Urgent,TVR,Death or,repeat MI,Death,MI,or any TVR,Incidence(%),p=0.01,RR 59%,p=0.19,p=0.42,p=0.02,p=0.25,p=0.047,Placebo(n=151),Abciximab(n=149),Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,ADMIRAL:30-Day Death,MI,or Urgent TVR,Placebo(n=151),14.6,6.0,Stent plus placebo,Cumulative incidence(%),8,12,14,16,0,2,4,6,10,Stent plus abciximab,0,5,10,15,20,25,30,35,Days,p=0.01,Abciximab(n=149),Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,ADMIRAL:6-Month Clinical Events,7.3,4.0,6.6,9.9,33.8,7.4,3.4,2.0,2.0,5.4,15.9,22.8,0,5,10,15,20,25,30,35,40,Death,MI,or urgent,TVR,Death,Repeat MI,Urgent TVR,Death or,repeat MI,Death,MI,or any TVR,Incidence(%),p=0.02,RR 53%,p=0.32,p=0.049,p=0.14,p=0.03,p=0.13,Placebo(n=151),Abciximab(n=149),Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,0,50,100,150,200,ADMIRAL:Cumulative Incidence of Death,MI,or Urgent TVR at 6 Months,Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,0-,4-,8-,12-,16-,Cumulative Incidence(%),Time since randomization(days),Placebo(n=151),Abciximab(n=149),15.9%,7.4%,p=0.02,ADMIRAL:Early Abciximab Administration,MICU=Mobile intensive care unit,ER=Emergency room,21.1,12.4,23.7,13.3,2.5,8.3,2.5,9.2,0,5,10,15,20,25,MICU or ER,30 day,ICCU or CL,30 day,MICU or ER,6 month,ICCU or CL,6 month,Patients(%),RR 88%,RR 33%,RR 89%,RR 31%,Placebo(n=151),Abciximab(n=149),ICCU=Intensive cardiac care unit,CL=Catheterization laboratory,Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,ADMIRAL:LVEF,53.9,57.0,57.0,61.1,50,52,54,56,58,60,62,24 h,6 months,LVEF(%),p0.05,p=0.05,Placebo(n=92),Abciximab(n=101),Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,ADMIRAL:30-Day Safety Data,0,3.3,1.3,1.3,0.7,12.1,4.7,1.3,0,2,4,6,8,10,12,14,TIMI major,bleeding,TIMI minor,bleeding,Platelets,100,000/L,Platelets,50,000/L,Incidence,(%),p=0.08,p=0.004,p=0.31,p=ns,Placebo(n=151),Abciximab(n=149),Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,ADMIRAL:Conclusions,In the ADMIRAL trial,early administration of abciximab(prior to sheath insertion)in patients with AMI was associated with:,Higher TIMI grade 3 flow than placebo,Higher rate of procedural success than with placebo,An improvement in left ventricular function as compared with placebo,Reduced incidence of the primary endpoint at 30 days and 6 months,as compared with placebo,ADMIRAL shows that abciximab improves outcomes for patients undergoing primary revascularization for AMI,even in specific subgroups who are usually excluded from clinical trials those with cardiogenic shock or small vessels,Montalescot,G et al.,N,Engl,J,Med,2001;,344,:1895903.,CADILLAC Study,The CADILLAC trial investigated the use of GPIIb/IIIa inhibitors with coronary PCI in AMI patients,1,2,Patients were randomized to stent or no stent and abciximab or no abciximab in a 2x2 factorial design,1,The primary endpoint was death,MI,ischemia-driven TVR,or disabling stroke(major adverse cardiac events MACE)at 6 months,2,Tcheng JE et al.,Circulation,2003;,108,:131623.,Ston