1. Richard Melsheimer Director, Medical Affairs Europe Centocor Eli Lilly and Company Coordinated Use of ReoPro and Drug Eluting Stents: Rationale and Evidence

2. Mechanism and timing of action Clinical effect/benefit Indicated patients NICE guidelines Finances On-going trials Coordinated - How? Coordinated Use of ReoPro and Drug Eluting Stents

3. Timing of Complications Associated with Percutaneous Coronary Interventions Coordinated Use of ReoPro and Drug Eluting Stents Restenosis Leading to TVR Late Myocardial Infarction Abrupt Closure Side Branch Occlusions Myocardial Infarction Early Mortality Subacute Thrombosis Late Mortality 0 – 7 days30 days to 1 year and beyond

4. Abciximab vs Stents What is ReoPro meant to do? Prevent thrombus formation Dissolve platelet-rich thrombus Improve procedural success Reduce peri-procedural MIs Cut the rate of ischemic events by 50% Reduce late mortality after PCI VS Coordinated Use of ReoPro and Drug Eluting Stents

5. Abciximab vs Stents What are stents meant to do? VS Secure a dissection Reduce restenosis by reducing elastic recoil Coordinated Use of ReoPro and Drug Eluting Stents

6. Abciximab vs Stents What are stents meant to do? VS Secure a dissection Reduce restenosis by reducing elastic recoil Reduce restenosis by reducing SMC proliferation Coordinated Use of ReoPro and Drug Eluting Stents

7. Complementary Benefit Coordinated Use of ReoPro and Drug Eluting Stents

8. In-Hospital Events Associated with DES Cypher Stent vs Bare Stent % of Patients p = NS p = 0.379 n = 1055 n = 238 Coordinated Use of ReoPro and Drug Eluting Stents

10. Physiological responses to trauma have not changed –Inflammation –Distal embolization –LV function –Side branch occlusions –Microvascular flow –Thrombus formation Other Complications and Considerations Coordinated Use of ReoPro and Drug Eluting Stents

11. Primary Endpoint- Death, MI, Urgent Intervention (30 Days) 30 10.8 6.9 1 NEJM 1994; 330:956-61 2 NEJM 1997; 336:1689-96 3 Lancet 1998; 352:87-92 0 16 12 8 4 0 030 Bolus Bolus + Infusion Placebo p = 0.008 12.8 8.3 16 12 8 4 0 0 p < 0.001 Placebo + Stent Abciximab + PTCA 5.3 Abciximab + Stent EPIC 1 EPILOG 2 EPISTENT 3 16 12 8 4 0 30 p < 0.001 Placebo 11.7 5.2 Abciximab* Days * low-dose heparin group % of Patients with Events Coordinated Use of ReoPro and Drug Eluting Stents

13. Clinical Outcomes - Target Lesion Revascularization 7 month*6 month 9 month RAVELSIRIUSTAXUS SRTAXUS MR p = ??p =0.043p = 0.006p < 0.001 0% TLR in CYPHER arm through RAVEL 1 YEAR F/U % of Patients 100%  75%  79%  62%  Coordinated Use of ReoPro and Drug Eluting Stents

14. Clinical Outcomes - Death 12 months6 month 9 month RAVELSIRIUSTAXUS SRTAXUS MR p = NS % of Patients 1.7 Coordinated Use of ReoPro and Drug Eluting Stents

15. 032599.1 Achenbach 15 3.1 2.0 JACC 2000; 35:922-28 p = 0.010 1 Year Survival in all Patients Following PCI With and Without Abciximab EPIC, EPILOG, and EPISTENT - Meta-Analysis Placebo Abciximab 050100150200250300350 0 1 2 3 4 Days of Randomization Death (%) n = 2,424 n = 4,110

16. Death through 3 years by Tertile of Risk Risk Tertile % Patients EPIC, EPILOG and EPISTENT Combined  0%  1.5%  2.3% LowModerateHigh

17. ReoPro –all patients undergoing PCI CYPHER Stent –patients with symptomatic ischemic disease, de novo lesion < 30 mm with reference diameter between 2.25 mm and 5.00 mm Indicated Patients? Coordinated Use of ReoPro and Drug Eluting Stents

18. ReoPro - usage reflects new NICE guidelines –50% of PCI - mainly high risk Cypher Stent –Predominantly high risk of restenosis –Diabetics –Long lesions –Diffuse disease –Restenotic lesions –Bifurcations –Left main Actual Use in Patients? Coordinated Use of ReoPro and Drug Eluting Stents

19. No. Complementary financially? Coordinated Use of ReoPro and Drug Eluting Stents

20. Enhanced Survival Benefit of Abciximab in Diabetics 1 Year Mortality in Diabetics Following PCI with and without Abciximab EPIC, EPILOG, and EPISTENT - Meta-Analysis 030120150210270300360 0 1 2 3 4 Days of Randomization Death (%) 5 6 6090180240330  2.0% p = 0.031 4.5 2.5 JACC 2000; 35:922-28 Placebo Abciximab n = 574 n = 888

21. 1-year Mortality in Diabetics Who Underwent Multivessel Intervention % of Patients Death 1-year Bhatt et al. JACC 2000;35:922-8 7.7 0.9 n = 65n = 108 p = 0.018 88 % reduction

22. Ongoing or Upcoming Trials Coordinated Use of ReoPro and Drug Eluting Stents

23. ACE –carbo-stent vs carbo-stent+ReoPro in primary PCI CARDIA CLEAREST Trials Coordinated Use of ReoPro and Drug Eluting Stents

26. Complementary Benefit Coordinated Use of ReoPro and Drug Eluting Stents

27. Conclusions Coordinated Use of ReoPro and Drug Eluting Stents 1. Reasons for using ReoPro in PCI have not changed. 2. Reasons for using (DE) stents have not changed. 3. These reasons are different. 4. Everything suggests these two therapies are complementary. 5. (As expected), drug-eluting stents have demonstrated dramatic reductions in TVR. 6. (As expected), ReoPro reduces early ischemic events and late mortality.