Emerging Data Regarding the Potential Benefits of Early Initiation of Clopidogrel Among ACS Patients C. Michael Gibson, M.S., M.D.

Inhibition of Platelet Aggregation Following Clopidogrel Administration Hochholzer W et al. Circulation. 2005;111

Clopidogrel Loading Dose Timing and Risk of MACE Log Odds of Death, MI or UTVR at 28 Days Placebo - 2 Clopidogrel P = 0.020 for treatment / timing interaction - 3 - 4 - 5 - 6 5 10 15 20 25 30 Hours Prior to PCI of Study Drug Loading Dose J Am Coll Cardiol 2006;47:939–43.

30 Day Primary Endpoint Adverse Events Influence of Thienopyridine Exposure – PCI pts 30 Day Primary Endpoint Adverse Events RR [95%CI] 0.81 (0.68-0.96) RR [95%CI] 0.96 (0.77-1.20) RR [95%CI] 0.50 (0.37-0.67) RR [95%CI] 1.07 (0.83-1.39) RR [95%CI] 1.37 (1.00-1.88) RR [95%CI] 0.61 (0.39-0.97) Thienopyridine Exposed Not Thienopyridine Exposed

CURE: Major Bleeding in CABG Patients Major or life-threatening bleeding w/in 7 days of CABG P=0.07 P=0.53 Clopidogrel stopped <5 days prior to CABG >5 days K.Fox et al, ESC 2002

ACUITY: Primary Outcomes in CABG Patients Patients with and without a thienopyridine administered in-hospital prior to CABG P=0.066 P=0.013 P=0.362 *Heparin=unfractionated or enoxaparin

30 Day Outcomes – CABG Patients by Thienopyridine Status Patients with and without a thienopyridine administered in-hospital prior to CABG Thieno (+) n=718 Thieno (-) n=820 P-value Resource Utilization Total LOS, median 12.1 9.0 <0.001 Pre-CABG LOS, median 4.6 2.5 Post-CABG LOS, median 6.9 5.8 Bleeding Endpoints Post CABG Major Bleeding 50.0% 50.5% 0.85 Post CABG Blood transfusions 38.2% 38.0% 0.96 24hr Chest Tube Output (median) 600.0 ml 550.0 ml 0.22