1、S.Chiu Wong MD,FACCAssociate Professor of MedicineWeill Medical College of Cornell UniversityDirector,Cardiac Catheterization LaboratoriesThe New York Presbyterian Hospital-Cornell CampusThe ACC Symposium at the Great Wall Meeting,Beijing ChinaOctober 17,2004Thrombolysis or Primary PCI in the Treatm
2、ent of Acute MI Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs.Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMIThrombolysis or PCI in AMI Summary Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs.Primary PCI Adjunct Pharmacology and Strat
3、egies Current Recommendations in Treatment of AMIThrombolysis or PCI in AMI Circulation,Volume XLV,January 1972.Page 215-230Coronary Arteries in Fatal AcuteMyocardial InfarctionBy WILLIAM C.ROBERTS,M.D.SUMMARY The coronary arteries are diffusely involved by atherosclerotic plaques in fatal acute myo
4、cardial infarction(AMI).The degree of luminal narrowing may vary but plaques are present in practically every millimeter of extramural coronary artery.Usually the lumens of at least two of the three major coronary arteries are narrowed 75%by old plaques in patients who die suddenly(75 yrs and treate
5、d 12 hrs from sx onset were.The earlier treatment initiation,the greater the benefit and thus re-affirm the concept of “time is muscle.”Not every patient is eligible for thrombolytic treatment Cerebral/vascular bleed Percent AMI pts with TIMI 3 flow following thrombolysis is less than ideal Thrombol
6、ysis or PCI in AMI Limitations of Thrombolysis in AMI PatientsThrombolysis or PCI in AMI Contraindications for fibrinolytics in AMIContraindicationsPrevious hemorrhagic stroke at any time;other strokes or cerebrovascular events within 1 yrKnown intracranial neoplasmActive internal bleeding(does not
7、include menses)Suspected aortic dissectionAdapted from Ryan TJ,et al.ACC/AHA guidelines for the management of patients with AMI.J Am Coll Cardiol 1996;28:13281428Relative contraindicationsSevere uncontrolled hypertension on presentation(blood pressure 180/110 mm Hg)or chronic history of severe hyper
8、tensionHistory of prior cerebrovascular accident or known intracerebral pathology not covered in contraindicationsCurrent use of anticoagulants in therapeutic doses(international normalized ratio 23);known bleeding diathesisRecent trauma(within 24 wk),including head trauma or traumatic or prolonged(
9、10 min)cardiopulmonary resuscitation or major surgery Noncompressible vascular puncturesRecent(within 24 wk)internal bleedingFor streptokinase/anistreplase:prior exposure(especially within 5 d2 yr)or prior allergic reactionPregnancy and Active peptic ulcerAdapted from Ryan TJ,et al.ACC/AHA guideline
10、s for the management of patients with AMI.J Am Coll Cardiol 1996;28:13281428Thrombolysis or PCI in AMI Contraindications for fibrinolytics in AMI Previous large-scale randomized thrombolytic studies would suggest that only 15-20%of Acute MI(AMI)patients are considered eligible for reperfusion therap
11、y by conventional criteria More recent observational studies*with broader inclusion criteria would estimate that approximately 45 to 50%of AMI pts were eligible(ie.12 hrs symptom onset,chest pain with 2mm ST in any 2 contiguous ECG leads or new LBBB)and 32-45%of pts actually received thrombolytic ag
12、ents.Thrombolysis or PCI in AMI Eligibility for Thrombolysis in AMI PatientsKarlson BW et al Circ 1990;82:1140-6,*French JK et al BMJ 1996;312:1637-41*Reikvm et al Int J Cardiol 1997;61:79-83 Not every patient is eligible for thrombolytic treatment Cerebral/vascular bleed and re-infarction Percent A
13、MI pts with TIMI 3 flow following thrombolysis is less than ideal Thrombolysis or PCI in AMI Limitations of Thrombolysis in AMI PatientsReteplaseN=8260Reteplase+Reopro N=8326OR(95%CI)P value30-day mortality5.9%5.6%0.95(0.84-1.08)0.43Re-MI up to 7 days3.52.30.66(0.72-0.93)75yrs1.12.11.91(0.95-3.84)0.
14、069Sever/Mod.Bleed2.34.62.03(1.7-2.42)0.0001Thrombolysis or PCI in AMI GUSTO V:Primary and Secondary Endpoints16,588 pts within 6hrs of STEMI randomized to standard dose of reteplase(n=8260)or-dose reteplase and full-dose Reopro(n=8328).The GUSTOV Investigators.Lancet 2001;357:1905-14 Not every pati
15、ent is eligible for thrombolytic treatment Cerebral/vascular bleed Percent AMI pts with TIMI 3 flow following thrombolysis is less than ideal Thrombolysis or PCI in AMI Limitations of Thrombolysis in AMI PatientsThe 90 Minute Wall:60%Rates of TIMI Grade 3 Flow%TIMI 3 Flow Incidence and Patho-anatomy
16、 of AMI Fibrinolysis for AMI Fibrinolysis Vs.Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMIThrombolysis or PCI in AMI Grines,C.L.et al.N Engl J Med 1993;328:673-679Thrombolysis or PCI in AMI PAMI:In-Hospital Reinfarction and Death395 Pts were enrolled in
17、12 sites with AMI within 12 hrs of symptom onset and randomized to immediate PTCA(n=195)vs.tPA(n=200)By 6 months,reMI or death had occurred in 15.8%of pts treated with tPA and 8.5%treated with PTCA(p=0.02).Thrombolysis or PCI in AMI Short(4-6wks)-term clinical Outcomes Post 1 PTCA Vs.ThrombolysisKee
18、ley et al,Lancet 2003;361:13-20Summary of 23 trials totaling 7,739 pts(PTCA=3,872 and Thrombolysis=3,867 pts)27%65%54%47%Thrombolysis or PCI in AMI Advantages and Disadvantages of 1 PTCA Vs.ThrombolysisAdvantagesDisadvantagesSuperior vessel patency and TIMI 3 flowLack of generalized availabilityEarl
19、y definition of coronary anatomy allows risk stratificationDelay in mobilizing cath labReduced rates of recurrent ischemia,re-MI,death,and strokeSkilled interventional cardiologys requiredImproved survival in high risk patientsNo large single mortality trial data availableReduced intracranial bleedS
20、horter length of hospital stayAllows reperfusion when thrombolytics are contra-indicated Incidence and Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs.Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMIThrombolysis or PCI in AMI Thrombolysis or PCI i
21、n AMI The ADMIRAL Trial Multi-center 300 pts randomized,double-blind placebo controlled study to demonstrate the superiority of abciximab over placebo in primary PTCA with stenting in acute myocardial infarctionMontalescot G et al NEJM 2001;344:1895-1903Thrombolysis or PCI in AMI ADMIRAL:Frequency o
22、f TIMI III FLOWP=0.01P=0.04P=0.33P=0.04Montalescot G et al NEJM 2001;344:1895-1903Thrombolysis or PCI in AMI ADMIRAL:Composite Endpoint 6 monthP=0.13Montalescot G et al NEJM 2001;344:1895-1903P=0.32P=0.049P=0.02Reopro improves coronary patency before stenting,and clinical outcome at 30 days and 6 mo
23、nthsN=149N=151Thrombolysis or PCI in AMI CAPTIM:Study DesignPrimary Composite Endpoint-30-day Death,Reinfarction,Disabling StrokeBonnefoy E,et al.Lancet 2002;360:825-9AMI within 6 hours1200 planned840 enrolledPrehospitalThrombolysisn=419PrimaryAngioplastyn=421Comparison of Angioplasty and Prehospita
24、l Thrombolysis in Acute Myocardial InfarctionThrombolysis or PCI in AMI CAPTIM:Study DesignP=0.61P=0.13P=0.12P=0.29Bonnefoy E,et al.Lancet 2002;360:825-9Primary PTCA was not better than pre-hospital thrombolysis with transfer for possible rescue PTCA in pts with 4 mm elevation),Sx 12 hrs5 PCI center
25、s(n=443)and 22 referring hospitals(n=1,129),transfer in 3 hrsLytic therapyFront-loaded tPA 100 mg(n=782)Death/Re-MI/Stroke at 30 DaysThrombolysis or PCI in AMI DANAMI-2:Study DesignPrimary PCIwith transfer(n=567)Primary PCIwithout transfer(n=223)Stopped early by safety and efficacy committeeAnderson
26、 HR et al NEJM 2003;349:733-42Death/MI/Stroke(%)LyticPrimary PCIP=0.0003P=0.002CombinedTransfer SitesP=0.048Non-Transfer SitesThrombolysis or PCI in AMI DANAMI-2:Primary ResultsRRR 45%LyticPrimary PCILyticPrimary PCIRRR 40%RRR 45%Anderson HR et al NEJM 2003;349:733-42LyticPrimary PCIP=0.35DeathThrom
27、bolysis or PCI in AMI DANAMI-2:ResultsLyticPrimary PCIP=0.15StrokeLyticPrimary PCIP0.0001Recurrent MIAnderson HR et al NEJM 2003;349:733-4296%OF PTS WERE TRANSFERRED FROM REFERRAL HOSP.TO INVASIVE CETNER WITHIN 2 HRSThrombolysis or PCI in AMI Prague 2:Long distant transfer vs.Thrombolysis in AMI Mul
28、ticenter Czech study involving 850 pts with ST elevation MI within 12 hrs of symptom onset.Primary end point was 30-day moratlity,and composite secondary end points were:death,re-MI,stroke at 30 days.Widimsky P et al Eur Heart J 2003;24:94-104Thrombolysis or PCI in AMI Prague 2:Long distant transfer
29、 vs.Thrombolysis in AMIP=0.12P=NSP0.02P 3 hrs of symptom onset,PCI results in better clinical outcome despite long distance transfer.Widimsky P et al Eur Heart J 2003;24:94-104Thrombolysis or PCI in AMI C-port:Key FindingsP=0.72P=0.04P=0.28P=0.03Aversano T et al JAMA 2002;287:1943-51 Time to Perfusi
30、on Volume of Hospital and experience of OperatorThrombolysis or PCI in AMIWhat Else is Important in AMI Treatment Strategy?Additional important parameters to maximize quality of care in the treatment of AMI patientsN=27,080,P 0.00001Thrombolysis or PCI in AMINRMI-2:Primary PCI Door-to-Balloon time v
31、s.MortalityDoor-to-Balloon Time(minutes)Thrombolysis or PCI in AMI Mortality rates with primary PCI as a function of PCI-related time delayP=0.006020406080100PCI-Related Time Delay(door-to-balloon-door to needle)-5051015Circle sizes=sample size of the individual studySolid line=weighted meta-regress
32、ion Nallamothu BK,Bates ER.Am J Cardiol.2003;92:824-662 minBenefitFavors PCIHarmFavors LysisFor Every 10 min delay to PCI:1%reduction in mortality difference towards lyticsMeta-analysis of 23 studies with 7419 pts Time to Perfusion Volume of Hospital and experience of OperatorThrombolysis or PCI in
33、AMIWhat Else is Important in AMI Treatment Strategy?Additional important parameters to maximize quality of care in the treatment of AMI patientsThrombolysis or PCI in AMINRMI-2:Hospital Volume of Primary PCI vs.Mortality N=4,740 14,078 8,262P=0.033P=0.00010.860.67 Incidence and Patho-anatomy of AMI
34、Fibrinolysis for AMI Fibrinolysis Vs.Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMIThrombolysis or PCI in AMI Thrombolysis or PCI in AMI Importance of Early Reperfusion Therapy in STEMIOutcomes Dependent Upon:Time to treatment-TIME IS STILL MUSCLE Early a
35、nd full restoration in coronary blood flow Sustained restoration of flow Thrombolysis or PCI in AMI Pharmacological ReperfusionAvailable ResourcesClass I1.STEMI patients presenting to a facility without the capability for expert,prompt intervention with primary PCI within 90 minutes of first medical
36、 contact should undergo fibrinolysis unless contraindicated.(Level of Evidence:A)Antman et al.JACC 2004;44:682.Thrombolysis or PCI in AMI Fibrinolytic TherapyClass I In the absence of contraindication,fibrinolytic therapyshould be administered to STEMI patients with symptom onset within the prior 12
37、 hours&ST elevation2.In the absence of contraindications,fibrinolytic therapyshould be administered to STEMI patients with symptom onset within the prior 12 hours and new or presumably new LBBB.(Level of Evidence:A)Antman et al.JACC 2004;44:682-3.Thrombolysis or PCI in AMI Primary Percutaneous Coron
38、ary InterventionClass I 1.General considerations:The procedure should be supported by experienced personnel in an appropriate laboratory environment(performs more than 200 PCI procedures per year,of which at least 36 are primary PCI for STEMI,and has cardiac surgery capability).(Level of Evidence:A)
39、Antman et al.JACC 2004;44:682.Thrombolysis or PCI in AMI Primary Percutaneous Coronary InterventionClass I 2.Specific Considerations:a.Primary PCI should be performed as quickly as possible,with a goal of a medical contactto-balloon or door-to-balloon time of within 90 minutes.(Level of Evidence:B)b
40、.If the symptom duration is within 3 hours and the expected door-to-balloon time minus the expected door-to-needle time is:i)within 1 hour,primary PCI is generally preferred.(Level of Evidence:B)ii)greater than 1 hour,fibrinolytic therapy(fibrin-specific agents)is generally preferred.(Level of Evide
41、nce:B)c.If symptom duration is greater than 3 hours,primary PCI is generally preferred and should be performed with a medical contactto-balloon or door-to-balloon time as brief as possible,with a goal of within 90 minutes.(Level of Evidence:B)Antman et al.JACC 2004;44:684Primary Percutaneous Coronar
42、y Intervention Facilitated PCIClass IIb1.Facilitated PCI might be performed as a reperfusion strategy in higher-risk patients when PCI is not immediately available and bleeding risk is low.(Level of Evidence:B)Antman et al.JACC 2004;44:686.Fibrinolytic Therapy Combination Therapy with GP IIb/IIIaCla
43、ss III1.Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase should not be given to patients aged greater than 75 years because of an increased risk of ICH.(Level of Evidence:B)Antman et al.JACC 2004;44:683.Adapted from Figure 3;Antman et al.JACC 2004;44:682
44、If presentation is 75 PPCI cases per year/Team experience 36 PPCI cases per year Delay to invasive strategyProlonged transport(Door-to Balloon)(Door-to-needle)time is 1 HRMedical contact-to-balloon time is than 90 minThrombolysis or PCI in AMIWhich Strategy to Choose?Adapted from Figure 3;Antman et
45、al.JACC 2004;44:682An invasive strategy is generally preferred if:Skilled PCI laboratory available with surgical backup Medical contact-to-balloon time is than 90 min(Door-to Balloon)(Door-to-needle time)is 1 hr High risk from STEMICardiogenic shockKillip class greater than or equal to 3 Contraindications to fibrinolysis,including increasedrisk of bleeding and ICH Late presentationSymptom onset was more than 3 hours ago Diagnosis of STEMI is in doubtThrombolysis or PCI in AMIWhich Strategy to Choose?
