1. Do Tirofiban And ReoPro Give Similar Efficacy Outcomes Trial Presented at AHA Scientific Sessions Nov. 15, 2000

2. 2 GP IIb/IIIa Inhibition in PCI Consistent reduction in adverse events Optimal outcome when combined with stents No comparative data between agents Presented at AHA Scientific Sessions Nov. 15, 2000

3. 3 Background EPIC2099Abciximab 8.3 12.8 EPILOG2792Abciximab 5.3 11.7 EPISTENT1603Abciximab 5.3 10.8 (stent arms only) IMPACT-II4010Eptifibatide 9.5 11.4 ESPRIT2064Eptifibatide 6.8 10.4 RESTORE2141Tirofiban 8.0 10.5 Odds Ratio Trial N AgentIIb/IIIaControl(95% CI) Trial N AgentIIb/IIIaControl(95% CI) 30-Day Death, MI, Urgent Revascularization % 0.00.51.02.0 Presented at AHA Scientific Sessions Nov. 15, 2000

4. 4 Characteristics of Tirofiban and Abciximab Tirofiban non-peptide 495 dalton MW recovery of platelet function: hours specific for IIb/IIIa receptor Abciximab monoclonal antibody 47,615 dalton MW recovery of platelet function: days binds to IIb/IIIa, MAC-1,  v  3 Presented at AHA Scientific Sessions Nov. 15, 2000

5. 5 Primary Hypothesis Tirofiban will have comparable efficacy to abciximab in reducing the incidence of adverse cardiac ischemic events during the first 30 days after intracoronary stent placement. Presented at AHA Scientific Sessions Nov. 15, 2000

6. 6 Statistical Considerations Sample size provides 88% power to declare tirofiban non-inferior to abciximab, based on the relative efficacy of abciximab to placebo in EPISTENT* * the upper bound of the 1-sided 95% C.I. for the odds ratio (tirofiban relative to abciximab) must be below 1.47. Presented at AHA Scientific Sessions Nov. 15, 2000

7. 7 Primary Endpoint 30 day composite of: – death – myocardial infarction CK-MB > 3x ULN in two samplesCK-MB > 3x ULN in two samples new Q wavesnew Q waves – urgent TVR PCI or CABG Presented at AHA Scientific Sessions Nov. 15, 2000

8. 8 Inclusion Criteria stable CAD or ACS, scheduled to undergo PCI in native vessel and/or graft with planned stent primary or rescue PCI for ST elevation MI increased risk of bleeding allergy, intolerance, or recent exposure to study medications creatinine > 2.5 mg/dl cardiogenic shock Exclusion Criteria Study Design Presented at AHA Scientific Sessions Nov. 15, 2000

9. 9 Tirofiban or Pbo Abciximab or Pbo Bolus + 18-24 hr infusion Bolus + 12 hr infusion PCI 30 Days Study Design ASA Clopidogrel* Heparin * Investigator’s discretion Primary Endpoint 6 Mos Long term follow up 1 Yr Presented at AHA Scientific Sessions Nov. 15, 2000

10. 10 Concomitant Medications Clopidogrel* –300 mg 2-6 hours pre-PCI (or immediately pre- PCI in patients with unknown anatomy) –75 mg daily for 29 days Heparin –70 U/kg IV bolus –ACT target of 250 seconds Aspirin * Investigator’s discretion Presented at AHA Scientific Sessions Nov. 15, 2000

11. 11 Study Drug Administration Study drug boluses administered at start of procedure Study drug infusions started immediately after completion of study drug boluses Presented at AHA Scientific Sessions Nov. 15, 2000

12. 12 Enrollment December 30, 1999 - August 25, 2000 151 sites; 18 countries 5308 patients randomized 4812 patients randomized and treated Presented at AHA Scientific Sessions Nov. 15, 2000

13. 13 Participating Sites Presented at AHA Scientific Sessions Nov. 15, 2000

14. 14 Baseline Demographics US (n)19501963 Ex-US (n)448451 age (yr)62.0 62.6 gender (M/F, %) 73/2774/26 diabetes (%)2524 hypertension (%) 6465 dyslipidemia (%) 7372 smoking (%) 6464 prior MI (%) 3939 prior PCI (%) 2930 prior CABG (%) 1717 Tirofiban Abciximab n = 2398n = 2414 Presented at AHA Scientific Sessions Nov. 15, 2000

15. 15 Indication for Procedure ACS (%)6363 Stable Angina (%)2221 Positive Stress Test (%)1112 Other (%)45 Tirofiban Abciximab n = 2398n = 2414 Presented at AHA Scientific Sessions Nov. 15, 2000

16. 16 Procedural Characteristics Patients with stent placed (%)9595 Stents/Patient1.31.3 Patients with thrombus present(%)109 Vein grafts (%)55 Restenotic lesion(%)55 Maximum ACT (median)281282 Tirofiban Abciximab n = 2398n = 2414 Presented at AHA Scientific Sessions Nov. 15, 2000

17. 17 Medications ASA pre-procedure (%)9999 Mean Heparin dose (U)63556461 Clopidogrel any pre-procedure (%)93.492.2 300 mg load pre-procedure(%)87.285.6 Study drug infusion duration (hrs)18.212.0 Tirofiban Abciximab n = 2398n = 2414 Presented at AHA Scientific Sessions Nov. 15, 2000

18. 18 Primary Endpoint 30 day Death, MI, Urgent TVR Upper bound of 95% confidence interval = 1.52 Non-inferiority boundary RR = 1.26 1.47 1.00 Abciximab better Tirofiban better p=0.037 RR = 1.26 Presented at AHA Scientific Sessions Nov. 15, 2000 Tirofiban Abciximab 30 day Death, MI, Urgent TVR (%)

19. 19 Primary Endpoint D/MI/Urgent TVR 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 0 2 4 6 8 10 Time (Days) Tirofiban Abciximab % Patients 7.55% 6.01% Presented at AHA Scientific Sessions Nov. 15, 2000

20. 20 Primary Endpoint Analysis p = 0.037 CompositeDeathMIDeath/MIUrgent TVR p = 0.04 p = 0.043 Presented at AHA Scientific Sessions Nov. 15, 2000 p = NS Event Rate %

21. 21 Primary Endpoint Analysis Primary composite endpoint Death/MI MI Death Urgent TVR Tirofiban Abciximab RR CI % % 1 Tirofiban betterAbciximab better 7.556.011.261.05,1.52 7.175.721.261.01,1,58 6.885.431.271.01,1.60 0.500.411.210.52, 2.81 0.830.661.260.65, 2.44 Presented at AHA Scientific Sessions Nov. 15, 2000

22. 22 Time to MI MIs within the first 72 hrs 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 Tirofiban Abciximab Time (Hours) 0 2 4 6 8 10 % Patients Presented at AHA Scientific Sessions Nov. 15, 2000

23. 23 Subgroup Analysis Diabetes No Diabetes Age < 65 Age > 65 Male Female 1 Tirofiban betterAbciximab better Tirofiban Abciximab RR CI % % 6.255.381.170.72, 1.90 7.946.201.291.01, 1.64 6.614.601.451.05, 2.01 8.717.841.110.82, 1.50 7.166.491.110.86, 1.43 8.664.691.851.19, 2.89 Presented at AHA Scientific Sessions Nov. 15, 2000

24. 24 Subgroup Analysis Pre-procedure Clopidogrel Yes No ACS non-ACS U.S. Ex-U.S. Tirofiban Abciximab RR CI % % 7.195.751.261.00, 1.58 12.669.041.400.73, 2.68 9.316.271.491.15, 1.94 4.525.560.820.54, 1.24 7.696.721.150.91, 1.45 6.922.882.431.27, 4.64 1 Tirofiban betterAbciximab better Presented at AHA Scientific Sessions Nov. 15, 2000

25. 25 Planned Stenting in Non-ACS Death / MI / Urgent TVR 30 Days In patients with planned stenting or non-ACS patients ReoPro and Aggrastat have shown similar event rates. % of Patients with Event Presented at AHA Scientific Sessions Nov. 15, 2000; EPISTENT Investigators; ESPRIT - Presented ACC March, 2000

26. 26 Substudy of U.S. vs International Primary Endpoint Results The separation between Tirofiban and Abciximab in the U.S. was 18 events in 3913 patients treated The separation outside the US was 18 events in the 899 patients treated Death / MI / Urgent TVR at 30 Days % of Patients with Event Presented at AHA Scientific Sessions Nov. 15, 2000

27. 27 U.S. - Primary Endpoint Presented at AHA Scientific Sessions Nov. 15, 2000 30 day Death, MI, Urgent TVR U.S. Cohort Upper bound of 95% confidence interval = 1.44 Non-inferiority boundary RR = 1.14 1.47 1.00 Abciximab better Tirofiban better

28. 28 Safety Analysis TIMI Major Bleeding IC hemorrhage TIMI Minor Bleeding Any TIMI bleeding Thrombocytopenia (< 100,000) RBC Transfusion Platelet Transfusion Tirofiban Abciximab P % % 1.170.95 0.4670.04 3.545.59 0.001 4.596.50 0.542.44 <0.001 1.421.49 0.460.50 Presented at AHA Scientific Sessions Nov. 15, 2000

29. 29 Conclusions Abciximab was superior to tirofiban in reducing the incidence of the primary endpoint of the trial: The composite endpoint of death / MI / urgent target vessel revascularization at 30 days after intracoronary stent placement. There were no differences in rates of TIMI major bleeding, but significant differences in minor bleeding and thrombocytopenia were observed favoring tirofiban. Presented at AHA Scientific Sessions Nov. 15, 2000

30. 30 Preliminary Cost Analysis The cost differential of Abciximab vs Tirofiban is on the average $1000 more per patient to use abciximab Based on TARGET –No difference in mortality, no cost per year of life saved, although trial not adequately powered to assess mortality –3 MIs are prevented per 200 patients with use of abciximab –Additional cost of treating 200 patients with abciximab instead of Aggrastat would be $200,000 –Cost per MI prevented: $66,666 (I.e. $200,000 / 3 pts)