Welcome Ask The Experts March 24-27, 2007 New Orleans, LA

Pretreatment with Thienopyridines C. Michael Gibson, MS, MD Associate Professor of Medicine Harvard Medical School Chief of Clinical Research Cardiology Division Beth Israel Deaconess Medical Center Boston, MA

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.

Cumulative Holter Monitor Ischemia 5 10 15 Bival & post PCI Clop (n=101) Pre vs post PCI clop Among bival pts From 4-24 hrs HR = 7.28 p = 0.04 Cumulative minutes of ischemia (minutes per patient) Bival & pre PCI Clop (n=112) Epti & post PCI Clop (n=220) Epti & pre PCI Clop (n=217) 6 12 18 24 Hours after end of PCI CM Gibson ACC 2007

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

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