1. TIMI 10A Protocol Design TNK- tPA Bolus ASA + IV Heparin (APTT 55-85) Follow-up Hosp. Discharge to 30 days Pt. with Acute MI < 12h End Points: Pharmacokinetics Coagulation parameters TIMI grade 3 flow at 90' TIMI frame count Major hemorrhage Allergic Events 8 Ascending TNK-tPA Doses: 5, 7.5, 10, 15, 20, 30, 40, 50 mg Cannon CP et al. Circulation 1995;92:I-415.

2. TIMI 10A TIMI Flow Grade at 90 Minutes Primary Results Cannon CP, TIMI 10A Investigators. Circulation 1997;95:351-6 TNK-tPA Dose

3. ASA, IV Heparin Randomize 30 Day Follow-up TNK-tPA 30mg Patient with Acute ST Elevation MI < 12 hours TNK-tPA 40mg TNK-tPA 50mg* t-PA 100 mg Angio 60, 75, 90 Mins *Stopped early Replaced with 40 mg TIMI 10B Protocol Design

4. TIMI 10B TIMI Flow Grade at 90 Minutes Primary Results Cannon CP for the TIMI 10B Investigators. Circulation 1998;98:2805-14 * 77% 79% 88% 82% N = 311 304 146 76

5. ASA, IV Heparin Randomize 30 Day Follow-up TNK-tPA 30mg Patient with Acute ST Elevation MI < 12 hours TNK-tPA 40mg TNK-tPA 50mg* *Stopped early Replaced with 40 mg ASSENT I Protocol Design

6. ASSENT I Primary Results Incidence of Stroke at 30 Days Van de Werf F, Cannon CP for the ASSENT 1 Investigators Am Heart J 1999;137:786-91

7. p = 0.046 p = 0.4 p = 0.01 Giugliano RP, Circ 1997;96:I-535 (abstract) TIMI 10B/ASSENT I ICH Pre/post Reduction in Heparin Adjunctive Therapy