ESPRIT Clinical Trial Commentary Dr Eric Topol Chairman and Professor, Department of Cardiology Director of the Joseph J Jacobs Center for Thrombosis and Vascular Biology at the Cleveland Clinic Dr Robert Califf Professor of Cardiology Associate Vice Chancellor for Clinical Research at Duke University

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ESPRIT trial Enhanced Suppression Of Platelet Receptor GP IIb-IIIa using INTEGRILIN Therapy GP IIb-IIIa inhibitors have repeatedly shown to be beneficial in percutaneous intervention these drugs have been used in less than half of all eligible patient in the past few years difference between small molecule GP IIb-IIIa inhibitors (eg:eptifibatide) and antibody inhibitors (eg:abciximab) was apparent ESPRIT trial designed after the IMPACT 2 study showed modest benefit with eptifibatide

ESPRIT trial early suspension “COR Therapeutics Inc and Schering-Plough Corporation today announced they would suspend enrollment in the ongoing ESPRIT trial after interim analysis showed a significantly lower rate - about 50% - of death and MI among patients randomized to receive eptifibatide (Integrilin), a IIb-IIIa inhibitor, during stenting procedures … ” heartwire / February 4, 2000 / ESPRIT study halted…

ESPRIT trial Enhanced Suppression Of Platelet Receptor GP IIb-IIIa using INTEGRILIN Therapy Lead investigator Dr James Tcheng, Duke University Patients undergoing nonurgent percutaneous coronary intervention with stenting were randomized to eptifibatide or placebo. Eptifibatide was given as a 180 µg/kg bolus, followed by a 2 µg/kg/min infusion, followed 10 minutes later by a second 180 µg/kg bolus. The infusion was continued for up to 24 hours.

ESPRIT trial “The preliminary results of ESPRIT not only ratify [the benefits of GP IIb-IIIa blockade], they do it with several exclamation marks.“ Dr Eric Topol Chairman and Professor Department of Cardiology Cleveland Clinic

ESPRIT trial Enhanced Suppression Of Platelet Receptor GP IIb-IIIa using INTEGRILIN Therapy Primary endpoint combined incidence of death, MI, urgent repeat intervention, need for bail-out GP IIb-IIIa inhibitor therapy at 48 hours Secondary endpoints composite endpoint and composite endpoint of death, MI, or urgent repeat revascularization at 12 hours, 24 hours, 7 days and 30 days original randomization to include 2400 patients

ESPRIT trial Enhanced Suppression Of Platelet Receptor GP IIb-IIIa using INTEGRILIN Therapy n= day endpoint Integrilin vs placebo p value Combined incidence of death and MI ~ 50% lower

ESPRIT trial significant results obtained for 30 day endpoint and as early as 48 hours after the procedure no excess of severe bleeding events with eptifibatide modest elevation in the rate of moderate bleeding, mostly femoral artery bleeding eptifibatide (Integrilin) costs $ , compared to abciximab (Reopro), which costs $

ESPRIT trial this trial is not a direct comparison of GP IIb- IIIa inhibitors 6-month and 1-year mortality data are unknown for unequivocal comparisons, would need a head-to-head randomized trial cost analyses should include benefit as a function of the length of infusion, since eptifibatide is a short-acting molecule

ESPRIT trial “The results of this study reinforce our conviction that GP IIb-IIIa inhibitors should be the standard of care for patients undergoing intracoronary stenting.” Dr Robert Califf Professor of Cardiology Associate Vice Chancellor for Clinical Research at Duke University heartwire / February 4, 2000 / ESPRIT study halted…

ESPRIT trial “The evidence was so strong before ESPRIT and now it goes to a whole other level. But it’s disenchanting at the very least to think that still more than half the patients aren’t getting the benefits of the therapy. So this trial has a phenomenal step in the right direction.“ Dr Eric Topol Chairman and Professor Department of Cardiology Cleveland Clinic

ESPRIT trial hospital pharmacy budgets are increasing substantially due to FDA approval of good drugs at record rates an avalanche of new drugs is anticipated with combinatorial chemistry and the human genome project choice of therapies and devices is an area where evidence based medicine, such as the ESPRIT trial, becomes increasingly important

EPISTENT trial mortality at 1 year Days from Randomization Days from randomization stent + placebo, n = 809 stent + abciximab, n = 794 balloon + abciximab, n = 796 % of Pts, Death % of pts, death 2.4% 2.1% 1.0% 57% p = 0.037