1. Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty Study (ARMYDA-2) Trial ARMYDA-2:ARMYDA-2:

2. High Loading Dose clopidogrel 600mg Pre-PCI n=126 High Loading Dose clopidogrel 600mg Pre-PCI n=126 ARMYDA-2 Trial Standard Loading Dose clopidogrel 300mg Pre-PCI  n=129 Standard Loading Dose clopidogrel 300mg Pre-PCI  n=129 255 patients with stable coronary artery disease or non-ST-elevation ACS prior to PCI Excluding those with Primary intervention for AMI, baseline levels CK-MB > upper normal limit, contraindications to antithrombotic/antiplatelet therapy, high risk bleeding, CABG in past 3 mos, or clopidogrel treatment within 10 days of randomization 23% female, mean age 64 years 13% received IIb/IIa inhibitors and 20% drug-eluting stents 255 patients with stable coronary artery disease or non-ST-elevation ACS prior to PCI Excluding those with Primary intervention for AMI, baseline levels CK-MB > upper normal limit, contraindications to antithrombotic/antiplatelet therapy, high risk bleeding, CABG in past 3 mos, or clopidogrel treatment within 10 days of randomization 23% female, mean age 64 years 13% received IIb/IIa inhibitors and 20% drug-eluting stents

3.  Primary Endpoint: Composite of death, MI, or target vessel revascularization (TVR) at 30 days  Secondary Endpoint: Post-procedural biomarker increase > upper limit of normal (CKMB>2 times upper limit of normal), peak CKMB, troponin I, and myoglobin post-procedure, occurrence of any vascular/hemorrhagic complication  Primary Endpoint: Composite of death, MI, or target vessel revascularization (TVR) at 30 days  Secondary Endpoint: Post-procedural biomarker increase > upper limit of normal (CKMB>2 times upper limit of normal), peak CKMB, troponin I, and myoglobin post-procedure, occurrence of any vascular/hemorrhagic complication ARMYDA-2 Trial

4. ARMYDA-2 Trial: Primary endpoint The primary composite endpoint of death, MI, target vessel revascularization was significantly lower in the high-dose clopidogrel group at 30 days There was one TVR in the high-dose group and no deaths in either arm Primary Composite of death, MI, and target vessel revascularization p = 0.041

5. ARMYDA-2 Trial: Secondary Endpoint p=0.038 p=0.002 The individual components of the secondary endpoint were also lower in the high-dose clopidogrel group than in the standard dose group p=0.021 3.0 4.9 Peak CKMB ng/mL Peak Troponin I ng/mL 0.33 0.81 Myoglobin ng/mL

6. ARMYDA-2 Trial: Secondary Endpoint Pre-treatment with high-dose clopidogrel was associated with a lower peri- procedural MI Peak CRP levels did not differ by treatment group Periprocedural CKMB increase > 2 times the upper limit of normal p = 0.014 Presented at ACC 2005

7. ARMYDA-2 Trial Summary Among patients with stable coronary artery disease or non- ST-elevation ACS about to undergo PCI with stenting there was a significant decrease in the primary composite endpoint of death, MI, and TVR in those who received the higher (600mg) dose of clopidogrel compared with 300 mg. The secondary composite endpoint of post-procedural biomarker increase > upper limit of normal, peak CKMB, troponin I, or myoglobin post-procedure was also lower in the high-dose clopidogrel group. Among patients with stable coronary artery disease or non- ST-elevation ACS about to undergo PCI with stenting there was a significant decrease in the primary composite endpoint of death, MI, and TVR in those who received the higher (600mg) dose of clopidogrel compared with 300 mg. The secondary composite endpoint of post-procedural biomarker increase > upper limit of normal, peak CKMB, troponin I, or myoglobin post-procedure was also lower in the high-dose clopidogrel group.

8. ARMYDA-2 Trial Summary There were no increase in the risk of major bleeding or transfusion in the high-dose clopidogrel group. There was 1 minor bleed in each dose group. This is the first randomized trial comparing high-dose clopidogrel to standard dose clopidogrel, which provides important data on a newly studied therapy. A larger trial would be necessary to fully evaluate safety and endpoints other than peri-procedural MI. There were no increase in the risk of major bleeding or transfusion in the high-dose clopidogrel group. There was 1 minor bleed in each dose group. This is the first randomized trial comparing high-dose clopidogrel to standard dose clopidogrel, which provides important data on a newly studied therapy. A larger trial would be necessary to fully evaluate safety and endpoints other than peri-procedural MI.