The document discusses different strategies for reperfusion in ST-elevation myocardial infarction (STEMI) patients, including primary percutaneous coronary intervention (PPCI), fibrinolysis, and PCI following fibrinolysis. It summarizes the TRANSFER-AMI trial which compared a "pharmacoinvasive" strategy of early PCI within 6 hours of fibrinolysis to standard treatment of PCI only for failed reperfusion in high-risk STEMI patients initially treated with fibrinolysis. The trial found the pharmacoinvasive strategy reduced the primary composite endpoint of death, reinfarction, or ischemia at 30 days with no increase in bleeding risks compared to standard treatment.

1. PCI after MI, When ? Ahmed Magdy, MD, FACC, FSCAI National Heart Institute, Cairo

6. Gersh, B. J. et al. JAMA 2005;293:979-986. 1)Time is myocardium 2)Infarct size is outcome Relationship Between Duration of Symptoms of MI Before Reperfusion Therapy, Mortality Reduction, and Extent of Myocardial Salvage Modified by collaterals,ischemic preconditioning,myocardial oxygen uptake, other vessels

7. Gersh, B. J. et al. JAMA 2005;293:979-986. 1)Time is myocardium 2)Infarct size is outcome Relationship Between Duration of Symptoms of MI Before Reperfusion Therapy, Mortality Reduction, and Extent of Myocardial Salvage Modified by collaterals,ischemic preconditioning,myocardial oxygen uptake, other vessels Symptom onset to hosp Arrival 2 hr Thrombolysis given, 2 ½ hr Symptom onset to balloon 3 ½ hr Thrombolysis induced reperfusion 3 ½ hr

8. Importance of Rapid Time to Treatment With Fibrinolysis in STEMI Time from onset of symptoms to treatment (hours) Absolute % difference in mortality at 35 days 3.5%  2.5%  1.8%   1.6%  0.5%  0.0 1.0 3.0 2.0 4.0 0 – 1 2 – 3 4 – 6 7 – 12 12 – 24 The Fibrinolytics Therapy Trialists’ collaborative group. Lancet . 1994; 343:311.

9. PCI In-hospital Mortality vs Door to Balloon Time Door to Balloon Time (hours) In-hosp Death Rate 0-1.4 1.5-1.9 2.0-2.9 >3.0 N= 2,322 Brodie BR, JACC 47, 2006 N=384 N=493 N=750 N=673

14. 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 P = 0.006 0 20 40 60 80 100 PCI-Related Time Delay (door-to-balloon - door to needle) Absolute Risk Difference in Death (%) -5 0 5 10 15 Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6

17. Thrombolytics are Frequently Used During Off Hours

23. Rescue PCI

25. Impact of TIMI Flow Pre-PCI on Infarct Size

26. Facilitated Angioplasty

33. Primary, secondary and bleeding end points in FINESSE End points Primary PCI (%) Abciximab +PCI%) (abcixima/ reteplase) -facilitated PCI (%) p, combined+ PCI vs primary PCI p, combin +PCIvs abciximab-facilitate Primary end point* 10.7 10.5 9.8 NS NS All-cause mortality 4.5 5.5 5.2 NS NS Complications of MI 8.9 7.5 7.4 NS NS Death 4.5 5.5 5.2 NS NS TIMI major bleeding 2.6 4.1 4.8 0.025 NS TIMI minor bleeding 4.3 6.0 9.7 <0.001 0.006

36. (Earlier ) Delayed PCI

37. OAT Occluded Artery Trial

38. OAT Occluded Artery Trial

39. Disadvantages of OAT

51. Post-Lysis PCI studies GRACIA-1 SIAM III CAPITAL MI CARESS P=0.001 P=0.0008 P=0.04 P=0.001 N=1436

53. T rial of R outine AN gioplasty and S tenting after F ibrinolysis to E nhance R eperfusion in A cute M yocardial I nfarction The TRANSFER-AMI trial Warren J. Cantor, David Fitchett, Bjug Borgundvaag, Michael Heffernan, Eric A. Cohen, Laurie J. Morrison, John Ducas, Anatoly Langer, Shamir Mehta, Charles Lazzam, Brian Schwartz, Vladimir Dzavik, Amparo Casanova, Paramjit Singh, Shaun G. Goodman on behalf of the TRANSFER-AMI Investigators

56. PCI Centre Cath Lab Community Hospital Emergency Department Cath / PCI within 6 hrs regardless of reperfusion status Cath and Rescue PCI  GP IIb/IIIa Inhibitor TNK + ASA + Heparin / Enoxaparin + Clopidogrel “ Pharmacoinvasive Strategy” Urgent Transfer to PCI Centre Assess chest pain, ST  resolution at 60-90 minutes after randomization ‘ High Risk’ ST Elevation MI within 12 hours of symptom onset Failed Reperfusion* Successful Reperfusion Elective Cath  PCI > 24 hrs later “ Standard Treatment” * ST segment resolution < 50% & persistent chest pain, or hemodynamic instability Repatriation of stable patients within 24 hrs of PCI Randomization stratified by age (≤75 vs. > 75) and by enrolling site

57. Procedures Cardiac Cath performed (%) Time- TNK to Cath (hrs) PCI performed (%) Stent used (% of PCI cases) Time- TNK to PCI (hrs) PCI within 6 hrs of TNK (%) PCI within 12 hrs of TNK (%) GP IIb/IIIa inhibitor use (%) Time- TNK to GP IIb/IIIa inhib. (hrs) IABP use (%) CABG performed (%) Standard Treatment (n=508) 82 27 (4, 69) 62 98 18 (4, 73) 38 47 53 11 (4, 63) 6 8 Pharmacoinvasive Strategy (n=522) 97 3 (2, 4) 84 98 4 (3, 5) 89 97 73 4 (3, 5) 7 6 PRELIMINARY

58. Selected Medications Used ASA 1 st 6 hrs Clopidogrel 1 st 6 hrs * Heparin Enoxaparin Beta Blocker 1 st 6 hrs ASA at discharge Clopidogrel at discharge Beta Blocker at discharge ACE Inhibitor at discharge Lipid Lowering at discharge Standard Treatment (n=508) 97 69 57 55 61 85 73 79 74 80 Pharmacoinvasive Strategy (n=522) 98 87 57 51 55 85 79 81 73 81 * p< 0.05 PRELIMINARY

59. 0 2 4 6 8 10 12 14 16 18 0 5 10 15 20 25 30 10.6 16.6 Days from Randomization % of Patients n=496 n=508 422 468 415 466 415 463 414 461 414 460 412 457 Primary Endpoint: 30-Day Death, re-MI, CHF, Severe Recurrent Ischemia, Shock PRELIMINARY OR=0.537 (0.368, 0.783); p=0.0013 Standard PCI > 24 hrs (n=496) Invasive < 6 hrs (n=508)

60. Components of Primary Endpoint Death Reinfarction Recurrent Ischemia Death/MI/Ischemia New / worsening CHF Cardiogenic Shock Standard Treatment (n=498) 3.6 6.0 2.2 11.7 5.2 2.6 Pharmacoinvasive Strategy (n=512) 3.7 3.3 0.2 6.5 2.9 4.5 P-Value 0.94 0.044 0.019 0.004 0.069 0.11 PRELIMINARY

61. Safety Endpoints - Bleeding Intracranial hemorrhage TIMI scale Major Major (non-CABG-related) GUSTO scale Moderate Severe Severe (non-CABG-related) Transfusions Standard Treatment (n=498) 1.2 4.6 3.2 2.2 1.4 1.2 5.5 Pharmacoinvasive Strategy (n=512) 0.2 4.3 2.2 3.5 0.6 0.6 7.1 P-Value 0.066 0.88 0.33 0.26 0.22 0.34 0.31 PRELIMINARY

67. PCI for AMI Strategies

68. In summary: European GL

69. Egypt COMBATMI 2010 March 24-26, Cairo Sheraton Hotel

70. 2010 4 th . Acute Cardiac Care Course EGYPT COMBAT MI 2010 Cairo Sheraton, March 24-26, 2010