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

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

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

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

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

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

Complementary Benefit Coordinated Use of ReoPro and Drug Eluting Stents

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

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

Primary Endpoint- Death, MI, Urgent Intervention (30 Days) NEJM 1994; 330: NEJM 1997; 336: Lancet 1998; 352: Bolus Bolus + Infusion Placebo p = p < Placebo + Stent Abciximab + PTCA 5.3 Abciximab + Stent EPIC 1 EPILOG 2 EPISTENT p < Placebo Abciximab* Days * low-dose heparin group % of Patients with Events Coordinated Use of ReoPro and Drug Eluting Stents

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

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

Achenbach JACC 2000; 35: p = Year Survival in all Patients Following PCI With and Without Abciximab EPIC, EPILOG, and EPISTENT - Meta-Analysis Placebo Abciximab Days of Randomization Death (%) n = 2,424 n = 4,110

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

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

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

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

Enhanced Survival Benefit of Abciximab in Diabetics 1 Year Mortality in Diabetics Following PCI with and without Abciximab EPIC, EPILOG, and EPISTENT - Meta-Analysis Days of Randomization Death (%)  2.0% p = JACC 2000; 35: Placebo Abciximab n = 574 n = 888

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

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

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

Complementary Benefit Coordinated Use of ReoPro and Drug Eluting Stents

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.