1. Xemilofiban 10 mg TID Xemilofiban 20 mg TID Placebo TID RandomizationRandomization Xemilofiban 20 mg Placebo PCI 30 to 90 min prior to PTCR Stented patients were assigned to receive either ticlopidine (if assigned to the placebo arm) or ticlopidine placebo (if assigned to an active therapy arm ) for 2 to 4 weeks. ASA was taken by all patients at doses between 80-325 mg per day 6 Month Follow-up The EXCITE Trial

2. Primary Efficacy Analysis (Death, MI, and Urgent Revascularization)

3. Comparison Among Oral Agents Roxifiban Orbofiban Sibrafiban Xemilofiban Trial Rocket OPUS-TIMI16SymphonyEXCITE IIb/IIIa selective ++++++++++++ Binding Tightly CompetitiveCompetitive Competitive bound “Off rate” 7 mins secondssecondsseconds Peak of Onset 3-6h4-6h4-6h2-3h Half-life 24 h8-10h 11h 4-5h Excretion Plt. Dissoc.RenalRenalRenal Dosing QD BIDBIDTID Low Peak/trough +++ +++++ Intra-pt variability +++++++ Inter-pt variability ++++++++ Plts < 50,000 <0.5% 0.6%<0.5%0.5% Plts Pro-aggreg. NoYes- Yes Roxifiban Orbofiban Sibrafiban Xemilofiban Trial Rocket OPUS-TIMI16SymphonyEXCITE IIb/IIIa selective ++++++++++++ Binding Tightly CompetitiveCompetitive Competitive bound “Off rate” 7 mins secondssecondsseconds Peak of Onset 3-6h4-6h4-6h2-3h Half-life 24 h8-10h 11h 4-5h Excretion Plt. Dissoc.RenalRenalRenal Dosing QD BIDBIDTID Low Peak/trough +++ +++++ Intra-pt variability +++++++ Inter-pt variability ++++++++ Plts < 50,000 <0.5% 0.6%<0.5%0.5% Plts Pro-aggreg. NoYes- Yes 2nd Generation1st Generation Oral IIb/IIIa inhibitors CP Cannon 2000

4. Oral Antiplatelet Therapy in the New Millennium l Future Directions - Oral IIb/IIIa inhibitors: 1. Need to optimize dosing è Mimic stable effect of IV drugs è Reduce inter- and intra-patient variability è ? Use bedside platelet test to adjust dose 2. Test “second generation” drugs (tight IIb/IIIa binding) l ASA and ADP antagonists l Proven benefit in large trials l Both decrease platelet activation l Combination ASA/Clopidogrel being tested l Future Directions - Oral IIb/IIIa inhibitors: 1. Need to optimize dosing è Mimic stable effect of IV drugs è Reduce inter- and intra-patient variability è ? Use bedside platelet test to adjust dose 2. Test “second generation” drugs (tight IIb/IIIa binding) l ASA and ADP antagonists l Proven benefit in large trials l Both decrease platelet activation l Combination ASA/Clopidogrel being tested CP Cannon 2000