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S. Chiu Wong MD, FACC Associate Professor of Medicine Weill Medical College of Cornell University Director, Cardiac Catheterization Laboratories The New York Presbyterian Hospital-Cornell Campus,The ACC Symposium at the Great Wall Meeting, Beijing China October 17, 2004,Thrombolysis or Primary PCI in the Treatment of Acute MI,Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs. Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMI,Thrombolysis or PCI in AMI Summary,Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs. Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMI,Thrombolysis or PCI in AMI,Circulation, Volume XLV, January 1972. Page 215-230,Coronary Arteries in Fatal Acute Myocardial Infarction By WILLIAM C. ROBERTS, M.D. SUMMARY The coronary arteries are diffusely involved by atherosclerotic plaques in fatal acute myocardial 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 (6 hours) from cardiac disease with or without myocardial necrosis. Coronary thrombi occur in about 10% of patients who die suddenly or in whom necrosis is limited to the left ventricular subendocardium, and in about 50% of patients with transmural myocardial necrosis. Coronary thrombi usually indicate the presence of shock or congestive heart failure or both during die development of myocardial necrosis. The infrequency of coronary thrombi in patients dying suddenly of cardiac disease and in those with transmural necrosis who never have shock or congestive heart failure suggests that the thrombi may be consequences rather than causes of AMI.,Thrombolysis or PCI in AMI Patho-Anatomy of AMI,Thrombolysis or PCI in AMI Patho-Anatomy of AMI,Thrombolysis or PCI in AMI Patho-Anatomy of AMI,Thrombolysis or PCI in AMI Pathophysiology of ST-Elevation MI,Results from stabilization of a platelet aggregate at site of plaque rupture by fibrin mesh,platelet,RBC,fibrin mesh,GP IIb-IIIa,MI generally caused by a completely occlusive thrombus in a coronary artery,Incidence and Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs. Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMI,Thrombolysis or PCI in AMI,Thrombolysis or PCI in AMI ISIS-2 (Second international study of infarct survival),Randomized trial comparing 1MU of iv streptokinase over 1 hr, oral aspirin, both, or neither among 17,187 pts with suspected AMI up to 24 hrs after onset of symptom. Significant reduction of mortality at 35 days was demonstrated for aspirin or streptokinase, and an additive beneficial effect with the 2 combined agents was noted.,ISIS-2 Collaborative Group. Lancet 1988;332:349360,Thrombolysis or PCI in AMI Thrombolytic Agents for AMI,Comprehensive overview of thrombolytic therapy on AMI on early (5-week) mortality from randomized trials of more than 1000 pts by the fibrinolytic collaborative group,FCG The lancet 1994;343:311-22,Thrombolytics are beneficial across a broad spectrum of AMI pts with STE or BBB perhaps with the exception in pts who were 75 yrs and treated 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,Thrombolysis or PCI in AMI Limitations of Thrombolysis in AMI Patients,Thrombolysis or PCI in AMI Contraindications for fibrinolytics in AMI,Adapted from Ryan TJ, et al. ACC/AHA guidelines for the management of patients with AMI. J Am Coll Cardiol 1996;28:13281428,Adapted from Ryan TJ, et al. ACC/AHA guidelines for the management of patients with AMI. J Am Coll Cardiol 1996;28:13281428,Thrombolysis 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 therapy 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 agents.,Thrombolysis or PCI in AMI Eligibility for Thrombolysis in AMI Patients,Karlson 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 AMI pts with TIMI 3 flow following thrombolysis is less than ideal,Thrombolysis or PCI in AMI Limitations of Thrombolysis in AMI Patients,Thrombolysis or PCI in AMI GUSTO V: Primary and Secondary Endpoints,16,588 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 patient 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 Patients,The 90 Minute Wall:,60% Rates of TIMI Grade 3 Flow,% TIMI 3 Flow,Incidence and Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs. Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMI,Thrombolysis or PCI in AMI,Grines, C. L. et al. N Engl J Med 1993;328:673-679,Thrombolysis or PCI in AMI PAMI: In-Hospital Reinfarction and Death,395 Pts were enrolled in 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. Thrombolysis,Keeley et al, Lancet 2003;361:13-20,Summary 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. Thrombolysis,Incidence and Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs. Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMI,Thrombolysis or PCI in AMI,Thrombolysis or PCI in 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 infarction,Montalescot G et al NEJM 2001;344:1895-1903,Thrombolysis or PCI in AMI ADMIRAL: Frequency of TIMI III FLOW,P=0.01,P=0.04,P=0.33,P=0.04,Montalescot G et al NEJM 2001;344:1895-1903,Thrombolysis or PCI in AMI ADMIRAL: Composite Endpoint 6 month,P=0.13,Montalescot G et al NEJM 2001;344:1895-1903,P=0.32,P=0.049,P=0.02,Reopro improves coronary patency before stenting, and clinical outcome at 30 days and 6 months,N=149,N=151,Thrombolysis or PCI in AMI CAPTIM: Study Design,Primary Composite Endpoint- 30-day Death, Reinfarction, Disabling Stroke,Bonnefoy E, et al. Lancet 2002;360:825-9,Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction,Thrombolysis or PCI in AMI CAPTIM: Study Design,P=0.61,P=0.13,P=0.12,P=0.29,Bonnefoy E, et al. Lancet 2002;360:825-9,Primary PTCA was not better than pre-hospital thrombolysis with transfer for possible rescue PTCA in pts with 6 hr onset of AMI,High-risk ST elevation MI patients (4 mm elevation), Sx 12 hrs 5 PCI centers (n=443) and 22 referring hospitals (n=1,129), transfer in 3 hrs,Lytic therapy Front-loaded tPA 100 mg (n=782),Death / Re-MI / Stroke at 30 Days,Thrombolysis or PCI in AMI DANAMI-2: Study Design,Primary PCI with transfer (n=567),Primary PCI without transfer (n=223),Stopped early by safety and efficacy committee,Anderson HR et al NEJM 2003;349:733-42,Death / MI / Stroke (%),Lytic,Primary PCI,P=0.0003,P=0.002,Combined,Transfer Sites,P=0.048,Non-Transfer Sites,Thrombolysis or PCI in AMI DANAMI-2: Primary Results,RRR 45%,Lytic,Primary PCI,Lytic,Primary PCI,RRR 40%,RRR 45%,Anderson HR et al NEJM 2003;349:733-42,Lytic,Primary PCI,P=0.35,Death,Thrombolysis or PCI in AMI DANAMI-2: Results,Lytic,Primary PCI,P=0.15,Stroke,Lytic,Primary PCI,P0.0001,Recurrent MI,Anderson HR et al NEJM 2003;349:733-42,96% OF PTS WERE TRANSFERRED FROM REFERRAL HOSP. TO INVASIVE CETNER WITHIN 2 HRS,Thrombolysis or PCI in AMI Prague 2: Long distant transfer vs. Thrombolysis in AMI,Multicenter 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;24:94-104,Thrombolysis or PCI in AMI Prague 2: Long distant transfer vs. Thrombolysis in AMI,P=0.12,P=NS,P0.02,P0.003,For pts within 3 hrs of symptoms, thrombolysis or transfer for PCI is comparable strategy. However, for pts present 3 hrs of symptom onset, PCI results in better clinical outcome despite long distance transfer.,Widimsky P et al Eur Heart J 2003;24:94-104,Thrombolysis or PCI in AMI C-port: Key Findings,P=0.72,P=0.04,P=0.28,P=0.03,Aversano T et al JAMA 2002;287:1943-51,Time to Perfusion Volume of Hospital and experience of Operator,Thrombolysis or PCI in AMI What Else is Important in AMI Treatment Strategy?,Additional important parameters to maximize quality of care in the treatment of AMI patients,N=27,080, P 0.00001,Thrombolysis or PCI in AMI NRMI-2: Primary PCI Door-to-Balloon time vs. Mortality,Door-to-Balloon Time (minutes),Thrombolysis or PCI in AMI Mortality rates with primary PCI as a function of PCI-related time delay,Circle sizes = sample size of the individual study Solid line = weighted meta-regression,62 min,Benefit Favors PCI,Harm Favors Lysis,For Every 10 min delay to PCI: 1% reduction in mortality difference towards lytics,Meta-analysis of 23 studies with 7419 pts,Time to Perfusion Volume of Hospital and experience of Operator,Thrombolysis or PCI in AMI What Else is Important in AMI Treatment Strategy?,Additional important parameters to maximize quality of care in the treatment of AMI patients,Thrombolysis or PCI in AMI NRMI-2:Hospital Volume of Primary PCI vs. Mortality,N=4,740 14,078 8,262,P=0.033,P=0.0001,0.86,0.67,Incidence and Patho-anatomy of AMI Fibrinolysis for AMI Fibrinolysis Vs. Primary PCI Adjunct Pharmacology and Strategies Current Recommendations in Treatment of AMI,Thrombolysis or PCI in AMI,Thrombolysis or PCI in AMI Importance of Early Reperfusion Therapy in STEMI,Outcomes Dependent Upon: Time to treatment-TIME IS STILL MUSCLE Early and full restoration in coronary blood flow Sustained restoration of flow,Thrombolysis or PCI in AMI Pharmacological Reperfusion,Available Resources Class I 1. STEMI patients presenting to a facility without the capability for expert, prompt intervention with primary PCI within 90 minutes of first medical contact should undergo fibrinolysis unless contraindicated. (Level of Evidence: A),Antman et al. JACC 2004;44:682.,Thrombolysis or PCI in AMI Fibrinolytic Therapy,Class I In the absence of contraindication, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours & ST elevation 2. In the absence of contraindications, fibrinolytic therapy should 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 Coronary Intervention,Class 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),Antman et al. JACC 2004;44: 682.,Thrombolysis or PCI in AMI Primary Percutaneous Coronary Intervention,Class 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. 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 Evidence: 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;44:684,Primary Percutaneous Coronary Intervention Facilitated PCI,Class IIb 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/IIIa,Class III 1. Comb

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