The ESPRIT Trial 6 Month and 1 Year Results James E. Tcheng, MD, FACC, FSCAI Duke Clinical Research Institute Duke University Medical Center Durham, NC

Eptifibatide Integrilin® (COR Therapeutics) Mpr - Har - Gly - Asp - Trp - Pro - Cys - C - NH2 constrained KGD cyclic heptapeptide Mpr = mercaptopropionyl, Har = homoarginyl derived from venom of Sistrurus m barbouri IV agent, blocks GP IIb/IIIa integrin half-life of 2–2.5 hours

Study Design eptifibatide 180+180 µg/kg bolus placebo ASA, thienopyridine <24°; randomization in cath lab eptifibatide 180+180 µg/kg bolus (boluses 10 min apart) 2.0 µg/kg-min infusion x18-24° + heparin 60 U/kg bolus (ACT 200-300 sec) placebo + heparin 60 U/kg bolus (ACT 200-300 sec) vs. elective (non-urgent) stent PCI 48 hour, 30 day, 6 month, 1 year follow-up primary endpoint: 48° death, MI, urgent TVR, thrombotic bailout key secondary endpoint (30d): death, MI, urgent TVR key secondary endpoint (6m, 1y): death, MI

Eptifibatide with ADP / PPACK Inhibition of Platelet Aggregation Study Drug Infusion IMPACT II % baseline aggregation 135 / 0.75 PURSUIT 180 / 2.0 20% 180 / 2.0 / 180 ESPRIT time

Key 6-Month Endpoint Cumulative Death, MI to 6 Months cumulative event rate (%) P=0.0015 37% log-rank statistic

cumulative event rate (%) 6 Month Death, MI, all TVR cumulative event rate (%) 18.5% p=0.0072 26% RRR 14.3% days

cumulative event rate (%) 1 Year Death, MI cumulative event rate (%) 37% RRR p=0.0010 12.4% 8.0% months

cumulative event rate (%) 1 Year Death, MI cumulative event rate (%) 37% RRR p=0.0010  = 0.9%  = 0.6% 30d-1yr =2.2% =1.7% 12.4% 11.5% 7.4% 10.2% 6.3%  = 1.3%  = 1.1% 8.0% months

cumulative event rate (%) 1 Year Death, MI, all TVR cumulative event rate (%) 22.1% 17.5% 24% RRR p=0.0068 months

cumulative event rate (%) 1 Year TVR by Diabetes 18.1% cumulative event rate (%) =2.0% 10% RR p=NS 16.1% 11.6% =1.2% 11% RR p=NS 10.4% months

ESPRIT Long-Term Follow-up Significant  in primary (48 hr) and key (30 day) composite endpoints consistent RRR across all components, subgroups Significant  in composite 6 mo and 1 yr endpoints Early (48 hr, 30 day) benefits sustained over time continued separation of curves of composite endpoints between 30 days and 1 year separation of curves driven by reductions in death and TVR (MI curves remain parallel) Early mortality benefit maintained to 1 year Effects consistent between diabetics, non-diabetics