急性心肌梗死的紧急干预课件.ppt

1、 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

2、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,hy

3、pertension,smoking,previous history of coronary artery disease(CAD),family history of CAD,and metabolic syndrome.An atherosclerotic plaque is shown obstructing a coronary arteryIn AMI,plaque spontaneously ruptures within the vessel.Platelets become activated,triggering the formation of thrombusThrom

4、bus present in the vessel is shown in this angiogramClumps of activated platelets can break off and travel downstream,blocking the microvessels and preventing blood from reaching the heart muscleSTEMI(ST-segment elevation MI)Ischemic symptoms lasting 30 mins(chest pain,dyspnea,etc.)On electrocardiog

5、ram(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 angiograph

6、ic appearance of thrombus 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 ho

7、urs.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.Abciximab has been studied in the following trials outlined in this presentation:RAPPORT1 Neumann et al.2

8、 ISAR-23 ADMIRAL4 CADILLAC5,6 ACE71.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 Eng

9、l J Med 2002;346:95766.7.Antoniucci D et al.J Am Coll Cardiol 2003;42:187985.Data from the studies outlined in this presentation will illustrate the effect that primary PCI with abciximab for AMI patients has on:Clinical outcomes1 Microvascular perfusion2 Left ventricular(LV)function1,2 Combined wit

10、h 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 days11.Montalescot G,Barragan P,Wittenberg O et al.N Engl J Med 2001;344:1895903.2.Neumann F-J,Blasini R,Schmi

11、tt C et al.Circulation 1998;98:2695701.Abciximab(represented as the teal green cloud entering the vessel)is shown flowing through a heavily artherosclerosed vesselIntervention with a balloon and stent results in the flattening and cracking of plaque,and the dislodging of sections of the plaqueAbcixi

12、mab prevents the thrombus formation that the intervention triggers.Blood flows freely and the PCI may proceed smoothly 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)

13、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)analysis1.Brener SJ et al.Circulation 1998;98:73441.*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 additio

14、nal 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 secondsHeparin*Abciximab*(n=241)Placebo*(n=242)AspirinActual treatment(AT)analysis(n=409)ITT anal

15、ysis(n=483)ST,AMI 12 hRandomize1 endpoint:death,recurrent MI or any TVR at 6 months by ITT analysis2 endpoint:death,recurrent MI,or urgent TVR at 7 and 30 days1.Brener SJ et al.Circulation 1998;98:73441.17.84.57.411.28.74.16.6051015202530Death,MI,or anyTVRDeath,MI,or urgentTVRDeathRepeat MIDeath orR

16、epeat MIUrgentTVRIncidence (%)p=0.048RR 35%p=0.82p=0.70p=0.36p=0.01p=0.9028.128.211.68.73.3Placebo(n=242)Abciximab(n=241)1.Brener SJ et al.Circulation 1998;98:73441.Placebo(n=242)Abciximab(n=241)9.911.217.83.35.811.6051015207-day30-day6-month*Incidence of death,MI,or urgent TVR(%)p=0.003RR 67%p=0.04

17、8RR 35%p=0.03RR 48%*6-month composite of death,MI,or urgent TVR was not a prespecified secondary endpoint1.Brener SJ et al.Circulation 1998;98:73441.051015207-day30-day6-monthIncidence of death,MI,or urgent TVR(%)10.512.019.92.84.610.6p=0.001RR 73%p=0.004RR 47%p=0.005RR 62%Placebo(n=191)Abciximab(n=

18、218)251.Brener SJ et al.Circulation 1998;98:73441.Abciximab(n=241)Placebo(n=242)9.507.916.6013.7024681012141618TIMI major bleedingIntracranialhemorrhageAll transfusionsIncidence(%)p=0.02p=0.04p=ns1.Brener SJ et al.Circulation 1998;98:73441.Abciximab reduced the major adverse outcomes death,reinfarct

19、ion,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 trial1.Brener SJ et al.Circulation 19

20、98;98:73441.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

21、 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 heparin1.Neumann F-J et al.C

22、irculation 1998;98:2695701.AMI 48 hHeparin(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)followe

23、d 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)RandomizeTiclopidine(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)1.Neu

24、mann F-J et al.Circulation 1998;98:2695701.0.440.1500.20.40.60.85662020406080p=0.007p=0.003n=79n=72n=72n=79p=0.024n=72n=8010.418.10510152025 peak flow velocity(cm/s)wall motion index(SD/Chords)Global LVEF(%)Usual care AbciximabCirc 1998;98:2695-701Neumann et al.Primary PCI for AMIUsual care(n=72)Abc

25、iximab(n=79)8.33.80123456789Blood transfusionsIncidence(%)p=0.321.Neumann F-J et al.Circulation 1998;98:2695701.Abciximab improved microvascular perfusion and recovery of contractile function LV function was improved in patients who received abciximab 1.Neumann F-J et al.Circulation 1998;98:2695701.

26、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 anal

27、yzed clinical outcome by the composite endpoint of death,recurrent nonfatal MI,and target lesion revascularization(TLR)1.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.AMI 48 hHeparin(5000 U)+aspirin(500 mg)Abciximab*(n=201)Usual care*(n=200)1 endpoint:late loss2 endpoint:composite of death,recur

28、rent 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)RandomizeTiclopidine(250 mg twice daily for four weeks)

29、Aspirin(100 mg twice daily throughout study)1.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.p=0.611.26 0.851.21 0.74Usual care(n=144)Abciximab(n=148)00.511.522.5Late loss(mm)1.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.Usual Care(n=200)Abciximab(n=201)10.56.04.51.55.05.02.52.00.53.0024681

30、012Any cardiaceventDeath orRepeat MIDeathNon-fatal MITLRIncidence(%)p=0.038RR 52%p=0.08p=0.16p=0.62p=0.301.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.HeparinMonth After Stent Placement1.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.05060708090100Global EF(%)*Absolute RR in adverse cardiac

31、 events 5.7%*Abciximab5.5%*P=0.17Event-Free Survival(%)012111012345678903.504.500.511.522.533.544.55StrokeBlood transfusionsIncidence(%)p=0.79Usual Care(n=200)Abciximab(n=201)p=ns1.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.No effect of abciximab on angiographic restenosis at 6 months was mea

32、sured 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 patients1.Neumann F-J et al.J Am Coll Cardiol 2000;35:91521.A multicenter,double-blind,randomized trial to reflect the com

33、mon 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 days1.Montalescot G et al.N Eng J Med 2001;34

34、4:1895903.Four coronary angiogramsAdmissionPost-PCI24 h post-PCI6 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 1.52.0 x control value)until the 24 h follow-up angiogram completedST,18 years oldFirst sympt

35、oms of AMI within 12 hours before enrollmentST-segment elevation 1 mm in at least 2 contiguous EKG leads Patients with small arteries or with cardiogenic shock were not excluded from this trial1.Montalescot G et al.N Engl J Med 2001;344:1895903.14.66.62.66.67.920.561.31.33.44.712.10510152025Death,MI

36、,or urgentTVRDeathRepeat MIUrgentTVRDeath orrepeat MIDeath,MI,or any TVRIncidence(%)p=0.01RR 59%p=0.19p=0.42p=0.02p=0.25p=0.047Placebo(n=151)Abciximab(n=149)1.Montalescot G et al.N Engl J Med 2001;344:1895903.Placebo(n=151)14.66.0Stent plus placeboCumulative incidence(%)8121416024610Stent plus abcix

37、imab05101520253035Daysp=0.01Abciximab(n=149)1.Montalescot G et al.N Engl J Med 2001;344:1895903.7.34.06.69.933.87.43.42.02.05.415.922.80510152025303540Death,MI,or urgentTVRDeathRepeat MIUrgent TVRDeath orrepeat MIDeath,MI,or any TVRIncidence(%)p=0.02RR 53%p=0.32p=0.049p=0.14p=0.03p=0.13Placebo(n=151

38、)Abciximab(n=149)1.Montalescot G et al.N Engl J Med 2001;344:1895903.0501001502001.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=0.02MICU=Mobile intensive care unitER=Emergency room21.112.42

39、3.713.32.58.32.59.20510152025MICU or ER 30 dayICCU or CL 30 dayMICU or ER 6 monthICCU or CL 6 monthPatients(%)RR 88%RR 33%RR 89%RR 31%Placebo(n=151)Abciximab(n=149)ICCU=Intensive cardiac care unitCL=Catheterization laboratory1.Montalescot G et al.N Engl J Med 2001;344:1895903.53.957.057.061.15052545

40、658606224 h6 monthsLVEF(%)p0.05p=0.05Placebo(n=92)Abciximab(n=101)1.Montalescot G et al.N Engl J Med 2001;344:1895903.03.31.31.30.712.14.71.302468101214TIMI majorbleedingTIMI minorbleedingPlatelets100,000/LPlatelets50,000/LIncidence(%)p=0.08p=0.004p=0.31p=nsPlacebo(n=151)Abciximab(n=149)1.Montalesco

41、t G et al.N Engl J Med 2001;344:1895903.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 c

42、ompared 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

43、 cardiogenic shock or small vessels1.Montalescot G et al.N Engl J Med 2001;344:1895903.The CADILLAC trial investigated the use of GPIIb/IIIa inhibitors with coronary PCI in AMI patients1,2 Patients were randomized to stent or no stent and abciximab or no abciximab in a 2x2 factorial design1 The prim

44、ary endpoint was death,MI,ischemia-driven TVR,or disabling stroke(major adverse cardiac events MACE)at 6 months21.Tcheng JE et al.Circulation 2003;108:131623.2.Stone GW et al.N Engl J Med 2002;346:95766.AMI 12 h,cardiogenic shock excluded(n=2681)Primary PTCA(n=518)MultiLink stent+abciximab(n=524)Mul

45、tiLink stent(n=512)Primary PTCA+abciximab(n=528)No Registryn=599(22%)Patients with high-risk coronary anatomyYesn=2082(78%)AngiographyDo patients meet angiographic criteria?Randomize1.Stone GW et al.N Engl J Med 2002;346:95766.AMI 350 s in non-abciximab-treated patients and 200-300 s abciximab-treat

46、ed patients until the 24 h follow-up angiogram was completed2 protocol-specified hypothesis:death,MI,ischemia-driven TVR,or disabling stroke at 30 daysProspectively defined 3 efficacy endpoints:composite MACE and its components at 1 year;myocardial salvage,restenosis,and infarct-artery reocclusion a

47、t 7 monthsAspirin,ticlopidine,and heparin*No abciximab(n=1030)Abciximab*(n=1052)1.Tcheng JE et al.Circulation 2003;108:131623.No abciximab(n=1030)Abciximab(n=1052)7.02.20.94.40.24.61.90.82.50.1012345678MACEDeathRepeat MI IschemicTVRDisablingstrokeIncidence(%)p=0.01p=0.49p=0.76p=0.02p=0.541.Tcheng JE

48、 et al.Circulation 2003;108:131623.No abciximab(1030)Abciximab(n=1052)0.41.500.40.81.21.6Subacute thrombosisIncidence(%)1.Tcheng JE et al.Circulation 2003;108:131623.p=0.0118.44.42.214.40.416.94.12.512.20.705101520MACEDeathRepeat MIIschemicTVRDisablingstrokeIncidence(%)p=0.29p=0.79p=0.64p=0.15p=0.4N

49、o abciximab(n=1030)Abciximab(n=1052)1.Tcheng JE et al.Circulation 2003;108:131623.3.402.33.90.62.40.14.55.00.40123456Severe bleedingModeratebleedingIntracranialhemorrhageThrombocytopenia(100,000 cells/mm3)Blood-producttransfusionIncidence(%)p=0.55p=0.16p=0.99p=0.008p=0.21No abciximab(n=1030)Abcixima

50、b(n=1052)1.Tcheng JE et al.Circulation 2003;108:131623.Patients treated with adjunctive abciximab during PCI significantly increased 30-day event-free survival.This was due mainly to a significant decrease in the rate of ischemia-driven TVR Abciximab reduced early ischemic subacute thrombosis and ab