1. TIMI 14 Antman et al. Circ 99: 2720,1999 Phases of Trial ControlInvestigational Accel tPA Accel tPA Accel tPA rPA (10 +10 U) rPA (10 +10 U) No lytic Abx + Abx + tPA tPA  SK Abx + 50 mg tPA + LD/VLD Heparin Abx + 50 mg tPA + LD/VLD Heparin Abx+  rPA + LD/VLD Heparin Abx+  rPA + LD/VLD Heparin tPA Phase (N= 888) (Circ 99 : 2720,1999) rPA Phase (N=299) tPA + rPA Pooled Database (N=1187)

2. TIMI 14 Antman et al. Circ 99: 2720,1999 ST , lytic eligible, < 12 h Control Full Dose Lytic: tPA 100 mg or rPA 10 + 10 U Reduced Dose Lytic  tPA, SK,rPA No Abciximab Abx: bolus 0.25 mg/kg inf 0.125  g/kg/min x 12 h Abx: bolus 0.25 mg/kg inf 0.125  g/kg/min x 12 h STD Heparin (70 U/kg ; 15 U/kg/h) ASA Low Dose Heparin (60 U/kg ; 7 U/kg/h) Very Low Dose Heparin (30 U/kg ; 4 U/kg/h) Angio (90 min), In Hospital Events, 30 day F/U Angio (90 min), In Hospital Events, 30 day F/U

3. TIMI 14 Antman et al. Circ 99: 2720,1999 TIMI 3 Flow (Core Lab) : 90 min

4. TIMI 14 Antman et al. Circ 99: 2720,1999 TIMI 3 Flow (Core Lab) : 90 min

5. TIMI 14 Antman et al. Circ 99: 2720,1999 Safety Observations: Dose Finding Phase N= 677 Major Hemorrhage* (6.6% --mostly instr.; ICH = 1.2%) tPA control 5% Abx alone3% tPA + Abx6% SK + Abx10% (dose related increase) Thrombocytopenia<100K <50K tPA Control3%0.6% Reperf. reg. with Abx7%1.4% Mortality (30 days) 4.0% --no important differences across groups Major Hemorrhage* (6.6% --mostly instr.; ICH = 1.2%) tPA control 5% Abx alone3% tPA + Abx6% SK + Abx10% (dose related increase) Thrombocytopenia<100K <50K tPA Control3%0.6% Reperf. reg. with Abx7%1.4% Mortality (30 days) 4.0% --no important differences across groups *Major Hemorrhage = ICH, Retroperitoneal, or Hg > 5 gm/dL  

6. TIMI 14 Antman et al. Circ 99: 2720,1999 Abciximab Improves the Speed and Extent of Thrombolysis: 60 + 90 min TIMI 3 Flow

7. TIMI 14 Antman et al. Circ 99: 2720,1999 Abciximab Facilitates Thrombolysis tPA Phase TIMI Frame Count- 60 min P=0.001 0 20 40 60 80 100 020406080 100 43 72 0 20 40 60 80 100 P=0.0009 tPA 100 mg TIMI 3 Flow- 60 min tPA 50 mg + Abx % Pts

8. TIMI 14 Antman et al. Circ 99: 2720,1999 TIMI 3 Flow : 90 min rPA Phase 10 + 10 U 87 88 75 5 + 5 U10 + 5 U % Pts N = rPArPA + Abx rPA dose

9. TIMI 14 Antman et al. Circ 99: 2720,1999 TIMI 3 Flow : 90 min tPA + rPA Phases 215 148 88 tPA 50 mg rPA 5 + 5 U % Pts N = Full Dose Lytic 50% Lytic+ Abx 87 tPA 100 mg rPA 10 + 10 U P=0.014

10. TIMI 14 Antman et al. Circ 99: 2720,1999 Determinants of TIMI 3 flow at 90 Min tPA + rPA pooled 0.215 TIMI 3 Flow (N=610) LAD Time (per hour) Abciximab More Likely Less Likely O.R. O.R. (95 CI) 0.93 (0.88,0.99) 1.57 (1.09,2.26) P=0.01 0.73 (0.51,1.04) Lytic Non Significant

11. TIMI 14 Antman et al. Circ 99: 2720,1999 Evaluation of Myocardial Perfusion 1. ST Resolution: Schr ö der JACC 26: 1657,1995 Complete (>70%) Partial (30-70%) None ( 70%) Partial (30-70%) None (< 30%) 2. TIMI Myocardial Perfusion Grade (MPG) 1. ST Resolution: Schr ö der JACC 26: 1657,1995 Complete (>70%) Partial (30-70%) None ( 70%) Partial (30-70%) None (< 30%) 2. TIMI Myocardial Perfusion Grade (MPG) CM Gibson Circulation 1999 TMP Grade 0TMP Grade 1TMP Grade 2TMP Grade 3 No or minimal blush Stain present. Blush persists on next injection Dye strongly persistent at end of washout. Gone by next injection Normal ground glass appearance of blush. Dye mildly persistent at end of washout

12. TIMI 14 Antman et al. Circ 99: 2720,1999 Abciximab Improves Myocardial Perfusion % Pts Complete (> 70%) ST RES--90 min P<0.001 N=125 N=221 TMPG 2/3 90 min P=0.08 N=33 N=66 de Lemos et al AHA 1999 C.M. Gibson 1999 tPA PhaserPA Phase

13. TIMI 14 Antman et al. Circ 99: 2720,1999 Conclusions Reperfusion regimens to achieve TIMI 3 flow: 1. Abciximab alone =  full dose SK alone 2. Abciximab augments rate and extent of thrombolysis with  dose lytics 60 min 90 min tPA tPA (50 mg) tPA tPA (50 mg) 100mg + Abx 100mg + Abx 60 min 90 min tPA tPA (50 mg) tPA tPA (50 mg) 100mg + Abx 100mg + Abx TIMI 3 Flow 43%  72%* 62%  77%* TIMI 3 Flow 43%  72%* 62%  77%* 3. Safety profile encouraging Reperfusion regimens to achieve TIMI 3 flow: 1. Abciximab alone =  full dose SK alone 2. Abciximab augments rate and extent of thrombolysis with  dose lytics 60 min 90 min tPA tPA (50 mg) tPA tPA (50 mg) 100mg + Abx 100mg + Abx 60 min 90 min tPA tPA (50 mg) tPA tPA (50 mg) 100mg + Abx 100mg + Abx TIMI 3 Flow 43%  72%* 62%  77%* TIMI 3 Flow 43%  72%* 62%  77%* 3. Safety profile encouraging * p=0.0009 unadjusted * p=0.01 unadjusted