1. 1 Advanced Angioplasty London, England 27 January, 2006 Jörg Michael Rustige,MD Medical Director Lilly Critical Care Europe, Geneva

2. 2 Results: Inhibition of Platelet Aggregation (IPA) at 24 Hours -20.0 0.0 20.0 40.0 60.0 80.0 100.0 Inhibition of Platelet Aggregation (%) Response to Drug 1 Drug 1 Responder Drug 1 Non-responder *Responder =  25% IPA at 4 and 24 h

3. 3 -20.0 0.0 20.0 40.0 60.0 80.0 100.0 Inhibition of Platelet Aggregation (%) Response to Drug 2 Response to Drug 1 *Responder =  25% IPA at 4 and 24 h Results: Inhibition of Platelet Aggregation (IPA) at 24 Hours

4. 4 -20.0 0.0 20.0 40.0 60.0 80.0 100.0 Inhibition of Platelet Aggregation (%) Response to Drug 2 Response to Drug 2 *Responder =  25% IPA at 4 and 24 h Results: Inhibition of Platelet Aggregation (IPA) at 24 Hours

5. 5 Comparative IPA (20  M ADP), 4 h Post Loading Dose n = 66

6. 6 0 20 40 60 80 100 024681012 Time (Hr) % IPA (20  M ADP) Thienopyridines: Speed of onset of action Eli Lilly and Company, Data on file Drug 1Drug 1 RespDrug 1 Non-Resp Drug 1 Drug 2 Drug 2 in 1 Resp Drug 2 in 1 Non-resp Drug 2

7. 7 1 0 EP: Significant Non-CABG Bleeding 30 D P= NS 3/25411/650 3/1994/2004/251 R/N P = 0.77 Prasugrel LD/MD Treatment Group Dose Ranging Clop. vs Prasugrel

8. 8 MACE: Time to Event Death, MI, CTVT, Stroke, and Recurrent Ischemia CLOPIDOGREL PRASUGREL Kaplan-Meier Estimate 0% 2% 4% 6% 8% 10% Time since PCI (days) 05101520253035 p = 0.26 9.4% 7.2% RR=0.77 [0.5, 1.2]

9. 9 STUDY DESIGN ACS (STEMI or UA/NSTEMI) & Planned PCI PRASUGREL 60 mg LD/ 10 mg MD PRASUGREL CLOPIDOGREL 300 mg LD/ 75 mg MDCLOPIDOGREL 1 o endpoint: CV death, MI, Stroke 2 o endpoints:CV death, MI, Stroke, Rehosp-Rec Isch CV death, MI, UTVR Median duration of therapy 12 months

10. 10 Early invasive treatment in NSTE-ACS

11. 11 NSTE-ACS Trop T pos Death, MI, or ACS Abciximab during all PCI procedures Selective invasive Early invasive Aspirin Enoxaparin Clopidogrel Statins CAG Medical Rx PCI / CABG Medical Rx CAG / PCI / CABG ETT Chest pain - 24 hrs Random. 0 hrs Refractory angina - + 24-48 hrs 1 year ICTUS Study Design

12. 12 10% 20% 30% 100200300 Early invasive Selective invasive Death, MI*, Rehospitalisation for ACS 21.7% 20.4% Relative Risk: 1.06 95% CI: 0.85 – 1.32 P = 0.59 Time (days) *Peak CK-MB > 1 x ULN; serial sampling every 6 hrs In patients with elevated CK-MB at randomization, at least 50% decrease with subsequent rise > 1 x ULN 1-year results of ICTUS

13. 13 Benefit of GP 2b/3a Agents in ACS Trials Meta-analysis of 6 major trials: Combined n = 31,402 Boersma et al Lancet 2002

14. 14 Trials of 2b/3a inhibition in PCI

15. 15 Kong D, et al. Am J Cardiol. 2003; 92:651-655. Placebo BetterIIb/IIIa Better TrialControl Treatment N 0.1110 RESTORE1.1%0.9% 12,940 EPILOG1.2%0.9% 4891 RAPPORT1.3%1.0% 5374 CAPTURE1.3%1.0% 6639 EPIC1.7%1.5% 2099 1.3%IMPACT I1.0% 6789 1.2%IMPACT II0.9% 10,799 ESPRIT1.0%0.8% 17,403 ISAR-21.1%0.8% 17,804 ADMIRAL1.2%0.8% 18,104 EPISTENT1.1%0.8% 15,339 1.3% CADILLAC 0.9% 20,186 Odds Ratio and 95% CI 0.73 (0.55, 0.96) P=0.024 Meta-analysis of Survival with Platelet GP IIb/IIIa Antagonists for PCI

16. 16 Mortality in Primary PCI Trials n = 400 ACE Circ 2004; 109:1704 % of Patients AHA2002, Oral Presentation CADILLAC Registry: In-hospital Mortality 8.3% without Abx; 4.7% with Abx Circ 1998; 98:734 n = 483 RAPPORT JACC 2000; 35:915 n = 401 ISAR-2 NEJM 2001; 41:1895 n = 300 ADMIRAL n = 2082 CADILLAC NEJM 2002; 346:957 6 Month1 Year6 Month 1 Year p = 0.82 p = 0.13p = 0.23p = 0.04p = NS Primary PCI for AMI

17. 17 FINESSE: Study Design Abciximab bolus ASA, unfractionated heparin 40U/kg (max 3000u) or enoxaparin (0.5 mg/kg IV + 0.3 mg/kg SC) – substudy only Abciximab bolusCombo Rx Primary PCI; Begin Abciximab Infusion Primary endpoint at 90 days: all-cause mortality, resuscitated VF occurring > 48H, cardiogenic shock, or readmission/ED visit for HF Door to Balloon (including transfer) > 60 min but < 4 hours Primary PCI with concomittant Abx Reteplase / Abciximab “facilitated PCI” Pre-PCI Abciximab “facilitated PCI” Acute MI patients with ST Elevation or New LBBB, < 6 hours of pain to qualifying ECG (N = 3000); Randomized 1:1:1