1. STEMI in the Cath Lab

3. Primary PCI angioplasty vs thrombolysis

5. primary PTCA vs thrombolysis randomized trials Zijlstra 1 Zijlstra 2 Ribeiro Grinfeld De Wood Grines Gibbons Ribichini Garcia GUSTO 2b 294 95 100 112 90 395 103 83 189 1138 total 2599

6. primary PTCA vs lysis in AMI PTCA n 1290 death reM I death/ reMI total stroke ICH 4.4% 2.9% 7.2% 0.7% 0.1% 6.5% 5.3% 11.9% 2.0% 1.1% lysis n 1316 0 0.5 1.5 1 2 odds ratio (95% CI) PTCA better lysis better 0.66 (0.46-0.94) 0.53 (0.34-0.80) 0.58 (0.44-0.76) 0.35 (0.14-0.77) 0.07 (0.00-0.43) 30-day outcomes WD Weaver JAMA 1997; 278: 2093-8 death 4.4% 6.5%

7. PTCA vs lysis 30 day death/reMI, subgroup analysis age <60 60-70 >70 PTCA 0.1 0.2 1 0.5 2 OR (95% CI) lysis DM yes no MI anterior non-anterior prior MI yes no 4.3% 6.3% 13.3% 9.2% 6.5% 8.2% 6.2% 9.7% 6.6% 8.2% 12.8% 23.6% 19.3% 11.8% 14.5% 12.0% 22.7% 11.5% PTCA better lysis better risk group low interm. high 2.9% 8.0% 13.1% 7.2% 12.7% 24.1% 23 15 8 10 16 13 16 8 7 27 15 8 NNT source: PCAT collaborators AHJ 2003;145:47-57

8. primary PTCA vs lysis 6-month outcomes: death/reMI 0 0.5 1.5 1 2 odds ratio (95% CI) PTCA death reMI death/ reMI lysis PTCA better lysis better 0.73(0.55-0.98) 0.46(0.34-0.64) 0.63(0.50-0.78) source: PCAT collaborators AHJ 2003;145:47-57 6.2% 4.8% 10.3% 8.2% 9.8% 16.3% death/ reMI 10.3% 16.3%

9. primary PCI vs lysis PTCA lysis p = 0.002 death p <0.001 reMI p < 0.0001 death/reMI/stroke 0 5 10 15 20 % patients EC KEELEY. JAMA 2003;361:13-20 long-term (6-18 m) outcomes 23 CRT (7739 pts)

11. Primary PCI POBA vs Stent

12. primary PTCA vs stent randomized trials FRESCO ZWOLLE GRAMI PAMI PASTA STENTIM-2 CADILLAC PSAAMI 150 227 104 900 136 211 1028 88 total 2844

13. primary PTCA vs stent 6-month outcomes 0 0.5 1.5 1 2 OR (95% CI) stent death reMI death/ reMI TVR death/reMI/TVR 3.3% 1.7% 4.9% 8.3% 13.7% 3.8% 3.0% 6.8% 18% 25.9% PTCA stent better PTCA better 0.85 (0.57-1.27) 0.58 (0.35-0.96) 0.72 (0.52-0.98) 0.41 (0.32-0.52) 0.45 (0.37-0.55) death/ reMI 4.9% 6.8%

14. number of events (death / reMI) prevented at 6-month F/U x 1000 patients treated thrombolysis STAT study JACC 2001;37:985-91 60 POBA 19 stenting POBA vs stenting vs 74

16. Survival Benefit by Time to Treatment with Lytics

18. Mortality by time to reperfusion with Primary PCI NRMI-2 Registry (27,080) C.P. CANNON. JAMA 2000;283:2941-7

27. After 12 hours??? BRAVE-2 Rationale: While thrombolysis has been shown to produce no benefit after 12 hours, no similar studies have looked at primary PCI in this group. Study: 365 patients randomized to in an invasive arm or a conservative arm. The invasive group underwent angiography and then PCI if necessary, while the conservative group was treated with conventional medical therapy. The primary end point was infarct size determined by SPECT at five to 10 days. Results: Infarct size (%LV) was significantly reduced in the invasive arm (8.0 vs 13%; p=0.002). No clinical differences. Kastrati ACC 2005

30. Role of GP 2b/3a inhibitors

32. GP IIb/IIIa Inhibitors For Primary PCI— 30-Day Death, (re)MI or Urgent Revascularization 26.1% 11.2% 9.7% 14.6% 4.5% 5.8% 2.0% 6.0% 0% 10% 20% 30% EPIC RAPPORT Neumann ADMIRAL Placebo GP IIb/IIIa p = 0.06 p = 0.03 p = 0.03 p = 0.01 N: 64 483 200 300 2082 6.8% 4.5% CADILLAC p = 0.02

35. the ADMIRAL study 61 58 64 57 61 57 abcix G. MONTALESCOT. NEJM 2001;344:1895-903 LV function at 24h 0 20 40 60 80 EF (%) placebo overall abcix placebo CCU/cath lab abcix placebo MICU/ER p<0.05 NS p<0.05

36. Eptifibatide Cutlip DE et al. Am J Cardiol 2001; 88: 62-4 Tirofiban Lee DP et al. Circulation 2003; 107: 1497-501 Other 2b/3a inhibitors

38. door-to-balloon times in primary PCI 8% 21% 24% 17% 10% 20% <60 60-90 120-150 90-120 150-180 >180 0 5 10 15 20 % of patients min C.P. CANNON. JAMA 2000;283:2941-7 NRMI-2 : 27080 consecutive patients

39. When patients present to a primary unit without interventional capabilities: Therapeutic options a) lytics b) “transfer” to a facility with a cardiac cath lab (with or without adjunctive therapy – “facilitated PCI” ). Any such “transfer” needs to be effected rapidly to take advantage of the early benefits of revascularization.

40. MAASTRICHT PRAGUE 1 DANAMI 2 PRAGUE 2 AIR PAMI thrombolysis vs transfer & primary PCI randomized trials n 150 200 1572 850 138 total 2910

41. MAASTRICHT PRAGUE 1 DANAMI 2 PRAGUE 2 AIR PAMI n 150 200 1572 850 138 lysis 6.7% 14.0% 7.6% 10.0% 12.1% PCI 6.7% 7.0% 6.6% 6.8% 8.4% 0.0 0.5 1.5 1 2.0 OR 95% CI lysis better PCI better 1.0(0.28-3.61) 0.45(0.17-1.17) 0.86(0.59-1.27) 0.65(0.40-1.07) 0.68(0.22-2.08) 30-day mortality thrombolysis vs transfer & primary PCI 0.74(0.57-0.98) p=0.03 8.8% 6.7% 2910 pooled

42. thrombolysis vs transfer & primary PCI † from admission min 50 100 150 200 t to treatment (from randomization) 0 MAASTRICHT DANAMI 2 PRAGUE 2 PRAGUE 1 AIR PAMI † thrombolysis 85 10 49 12 51 PCI 100 80 99 94 155

43. thrombolysis vs transfer & primary PCI 0 50 100 150 min 65 33 pooled thrombolysis PCI 41 106 57 90 10 CRT’s

47. ISAM, INJECT, HIT 4 data (3912 patients) partial (30- 70%) absent (<30%) complete (>70%) 30-day mortality by ST segment resolution at 180 min 2.7% 4.7% 13.5% 0 5 10 15 death % ST  seg resolution

48. Belenkie RESCUE PRAGUE Vermeer rescue PCI in acute MI randomized trials 28 151 200 149 total 528

49. rescue PCI short term outcome: death Belenkie RESCUE PRAGUE Vermeer n PCI cons. 28 151 200 149 6.3% 5.1% 7% 8.7% 33.3% 9.6% 14.0% 6.7% 0 0.5 1.5 1 2.0 odds ratio (95% CI) 0.13 (0.01-1.40) 0.51 (0.12-2.06) 0.46 (0.16-1.30) 1.24 (0.31-4.49) 0.55 (0.30-1.01) p=0.052 total 528 6.7% 11.5%

50. CAPTIM – Prehospital tPA vs 1 ° PCI 1 Year Results Bonnefoy Lancet 2002 P=0.27 Death at 1 Year Pre Hospital Lysis Primary PCI Pre Hospital Lysis Primary PCI P=0.09 Incidence of Shock

51. Studies of early angioplasty after thrombolytics GRACIA I

53. - While primary PCI appears superior to thrombolysis in direct comparison studies, few patients have prompt access to the cath. lab. rationale - treatment delays are common and likely reduce the true benefit of PCI - TIMI 3 grade flow prior to PCI is a determinant of success rate and clinical outcomes

54. Effect of Pre-procedural TIMI Flow on Cumulative Late Mortality after Primary PTCA 100% 98% 96% 94% 92% 90% 0 1 2 3 4 5 6 0.5% 2.8% 4.4% log-rank P for trend = 0.009 Grade 3 Grade 2 Grade 1 Months N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent Survival (%) Stone Circ 2001 6-Month Mortality

55. multivariate predictors of death GW STONE. Circulation 2001; 104:636-41 age (continuous) anterior MI female gender 3-vessel disease pre-PCI TIMI 0-2 flow OR (95% CI) 1.06 (1.02-1.10) 4.6 (2.1-10.0) 3.3 (1.6-6.7) 2.5 (1.2-5.6) 2.1 (1.2-37) p 0.001 0.001 0.008 0.01 0.04 pre-PCI TIMI 0-2 flow 2.1 (1.2-37) 0.04

56. TIMI 0 Complete occlusion TIMI 1 Penetration of obstruction by contrast but no distal perfusion TIMI 2 Perfusion of entire artery but delayed flow TIMI 3 Full perfusion, normal flow Mortality at 42 Days P < 0.005 TIMI 1 OPEN ARTERY THEORY: Better flow in the infarct artery improves survival Chesebro JH et al. Circulation 1987;76:142-54

57. Early TIMI 3 Flow with Combination Therapy 66 72 54 56 47 40 43 39 0 10 20 30 40 50 60 70 80 Full-Dose Lytic GP IIb/IIIa +Lytic % TIMI 3 Flow (60-90 mins) IMPACT-AMI TIMI-14 SPEED INTRO-AMI Full-Dose t-PA + t-PA + r-PA + t-PA + Eptifibatide Abciximab Abciximab Eptifibatide

58. Facilitated angioplasty studies

59. Half-Dose t-PA Before PCI: PACT Trial (n=606) 61* 34 % Patients Ross JACC 1999 * * *p < 0.001 vs placebo LVEF 58.4% 58.2% Rec Ischemia 13.5% 17.9% Reocclusion 3.7% 5.9% Major Bleed 13.5% 12.9% Death at 30d 3.3% 3.6% P = NS

61. facilitated PCI randomized trials n 6000 4000 1900 4000 200 507 100 6000 ADVANCED- MI ASSENT PCI CARESS FINESSE GRACIA 2 ON-TIME TIGER-PILOT TIGER study ½ TNK+eptif/early eptif TNK+enox/adj. GPIIb/IIIa ½ rPA+abcix • / ½rPA+abcix ½rPA + abcix/early abcix/adj.abcix TNK+enox/adj.abcix pre-hosp tirofiban/cath lab tirofiban ER tirofiban/cath lab tirofiban ½TNK+tirofiban • / ½TNK+tirofiban treatments • PCI to be performed only in case of no ST-segment resolution

62. Main Results of ADVANCE-MI Giugliano AHA 2004 P = 0.09 P = 0.02 Trial stopped after 149 patients randomized !

64. survival (%) follow up (days) 0 80 90 100 400 600 800 survival in TIMI 3 flow patients 1200 1400 JPS HENRIQUES. Circulation 2003;107:2115-9 200 MBG 2/3 n 823 1000 MBG 0/1 n 101 *p<0.001 *log rank:20.55, p>0.001

67. CRT’s of agents designed to improve tissue reperfusion result - - - - - + + - - - - - agent metoprolol prostacyclin fluosol magnesium rheoth Rx abciximab adenosine Hu 23F2G glucose/insulin/K AMP 579 pexelizumab pexelizumab TIMI 2 TIMI 4 TAMI 9 ISIS 4 CORE MUNICH AMISTAD HALT MI ECLA ADMIRE COMPLY COMMA n 1.390 50 430 58.050 2.780 200 236 420 407 311 920 814 trial

68. effect of GP IIb/IIIa inhibition on recovery of CBF and LV function •  peak CBF (cm/sec) 0 10 abcix 20 18.1 10.4 control N 80 N 72 0 0.2 0.4 abcix control N 79 N 72 0.44 0.15 F.J. NEUMANN. Circulation 1998;98:2695-2701 p=0.024 •  wall motion index (SD/chord) p=0.007 • 2 weeks F/U vs post PCI measurements

69. the AMISTAD trial infarct size KW MAHAFFEY. JACC 1999;34:1711-20 0 50 aden n 72 placebo n 72 15% 45% % of LV 20 10 30 40 anterior MI % of LV 0 10 aden n 119 20 13% 20% placebo n 117 5 15 all

70. i.c. adenosine as adjunctive to PCI CRT adenosine vs placebo (n 54) M. MARZILLI. Circulation 2001;101:2154-9 TIMI 3 grade flow 0 50 aden 100 100% 70% placebo 25 75 0 10 30 aden placebo 3.7% 26% no reflow 20

71. direct stenting n 102 angio end point slow flow (TIMI 3  2) no-flow (TIMI 0-1) distal embolization clinical outcomes (6-m F/U) death re-MI TVR direct stenting in acute MI C. LOUBEYRE et al. JACC 2002;39:15-21 11.7% 2.9% 4.9% 3.9% 0.9% 2.9% 8.8% pre- dilatation n 104 26.9% 12.5% 7.6% 6.7% 3.8% 3.8% 6.7% p=0.01 p=0.02 angio end point 11.7% 26.9% slow flow (TIMI 3  2) 2.9% 12.5%

72. endovascular cooling SR DIXON. JACC 2002;40:1928-34 COOL-MI n 400 pts % pts 0 MACE 10 0% 10% median infarct size 2% 8% % LV 5 0 10 5 cooling n 21 control n 21

73. new cathether-based techniques CRTs in AMI X-AMINE AIMI EMERALD N 200 N 500 PROMISE N 200 thrombectomy distal protection mechanism device X-SIZER • ANGIOJET PERCU-SURGE FILTER-WIRE

75. delayed PTCA for occluded IRA’s outcomes: death TAMI 6 TOMIIS Pfisterer Hori TOAT all short term 1 year F/U Pfisterer Hori TOAT all 71 44 16 66 66 263 n 16 66 66 148 8.8% 4.0% 0 0 0 3.2% PTCA 0 0 0 0 5.4% 5.0% 0 5% 0 3.6% cons. 0 5.0% 0 3.2% 0 0.5 1.5 1 2 PTCA better cons. better 1.69(0.21-15.7) 0.75(0.02-29.85) 0.0(0.0-3.64) 0.87(0.19-3.82) 0.0(0.0-3.64) OR 95% CI 0.01(0.0-4.4)

77. Apoptotic Rate in Occlued vs Open IRA Abbate A et al. Circulation 2002