1. TIMI 30: The PROTECT Trial High-risk UA/NSTEMI for PCI of a native coronary artery with either DM; or + Troponin; or ST   0.5 mm; or TRS > 3 Bivalirudin 0.75 mg/kg IVB + 1.75 mg/kg/h Eptifibatide 180/180  g/kg + 2  g/kg/min Low Dose UFH 50 U/kg IVB ACT 200-250 + Low Dose Enoxaparin 0.5 mg/kg IV + TRANSFER TO CATH LAB, DIAGNOSTIC ANGIOGRAM CONFIRM ELIGIBLE FOR PCI OF CULPRIT IN NATIVE ARTERY N = 857 Randomization stratified by Clopidogrel pretreatment >6 h and ≤6 h If not pretreated, then 300 mg Clopidogrel immediately prior to stenting. All tx’d with ASA If not pretreated, then 300 mg Clopidogrel immediately prior to stenting. All tx’d with ASA

2. n=55 p < 0.001 Mean Duration of Ischemia (minutes) Death or MI No Death or MI n=732 n=76 Death or MI (%) n=711 Ischemic event on Holter No Ischemic Event on Holter p < 0.001 Association of Holter Monitor Findings with Death / MI HSC Symposium ACC 2005

3. Time from First Eptifibatide Bolus to Major or Minor Bleeding Time from first bolus to bleed (hours) Median time from first bolus to bleed = 7.0 hrs, IQ 3.1-14.0 N=16 bleeds Kirtane, Murphy, and Gibson HSC Symposium ACC 2005

4. CrCl (ml/min) Relation of Creatinine Clearance to Major or Minor Bleeding with Eptifibatide p=0.01 Kirtane, Murphy, and Gibson Bleed: Median CrCl 74.6, IQ 55.3-100.1 No bleed: Median CrCl 95.5, IQ 72.1-121.0 n=18 n=548 HSC Symposium ACC 2005

5. Serum Creatinine (mg/dL) Bleed: Median Creatinine 1.0 IQ 0.9-1.2 No bleed: Median Creatinine 1.0, IQ 0.8-1.1 Relation of Serum Creatinine to Major or Minor Bleeding with Eptifibatide p=0.49 Kirtane, Murphy, and Gibson n=18 n=548 HSC Symposium ACC 2005

6. Age Relation of Age to Major or Minor Bleeding with Eptifibatide Kirtane, Murphy, and Gibson Bleed: Median age 69 years No bleed: Median age 59 years p=0.002 n=18 n=555 HSC Symposium ACC 2005

7. Frequency of Non-Cr Cl Dose Adjusted Infusion Among Patients with Reduced Renal Function in PROTECT P=0.51 Per the protocol, the infusion dose was to be reduced for patients with CrCl  50 ml/min (Eptifibatide) or CrCl<60 ml/min (Bivalirudin) Kirtane, Murphy, and Gibson N=35 N=32 HSC Symposium ACC 2005

8. Relation of Dose Adjustment of Eptifibatide Infusion to Bleeding Outcomes Major/Minor Bleeding Transfusion P=0.028 P=0.009 No bleeding events or transfusions occurred among patients with CrCl  50 ml/min who received a reduced-dose infusion Kirtane, Murphy, and Gibson CrCl>50 CrCl  50 CrCl>50 N=530 N=530 % Major / Minor Bleeding % Transfusion HSC Symposium ACC 2005 N=17 N=17 N=18 N=18 N=530 N=530 N=17 N=17 N=18 N=18

9. Bleeding in PROTECT Half the bleeds occurred after 6 hours of infusion Half the bleeds occurred after 6 hours of infusion Increasing age and a failure to dose-adjust the eptifibatide infusion in patients with reduced Creatinine Clearance (CrCl)  50 mg/dL (not Cr or weight) were the strongest independent correlates of bleeding events Increasing age and a failure to dose-adjust the eptifibatide infusion in patients with reduced Creatinine Clearance (CrCl)  50 mg/dL (not Cr or weight) were the strongest independent correlates of bleeding events A failure to adjust the eptifibatide dose for CrCl rather than Cr occurred in 17/35 (48.5%) of patients with reduced CrCl, and this was associated with a five-fold greater incidence of bleeding events (17.7% vs. 2.7%, p=0.014) A failure to adjust the eptifibatide dose for CrCl rather than Cr occurred in 17/35 (48.5%) of patients with reduced CrCl, and this was associated with a five-fold greater incidence of bleeding events (17.7% vs. 2.7%, p=0.014) HSC Symposium ACC 2005