1. Name of the speaker: Germano DiSciascio I have the following potential conflicts of interest to report:  Consulting  Employment in industry  Stockholder of a healthcare company  Owner of a healthcare company  Other(s)  I do not have any potential conflict of interest TCT 2007 – Disclosure Slide

2. ARMYDA-5 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study Prospective, multicenter, randomized trial investigating influence on outcome of in-lab 600 mg clopidogrel loading vs 6-hour pre-PCI treatment – “ARMYDA-Preload” Principal Investigators: Giuseppe Patti, Vincenzo Pasceri, Giuseppe Colonna Investigators: Antonio Montinaro, Leonardo Lassandro Pepe, Francesco Ciccirillo, Laura Gatto, Fabio Mangiacapra, Antonio Tondo, Andrea D’Ambrosio, Annunziata Nusca, Giordano Dicuonzo, Gennaro Sardella, Bibi NGuyen Chairman: Germano Di Sciascio

3. 30-day Death, MI, TVR (%) ARMYDA-2 RESULTS Primary end-point Circulation 2005;111:2099-2106 P=0.041 4% 12%

4. ARMYDA-5: BACKGROUND  The ARMYDA-2 trial demonstrated a 61% RR of MACE in patients undergoing PCI pretreated (mean 6 hrs) with 600 mg clopidogrel loading, compared with a 300 mg dose  Concerns about surgical bleeding (with preloading), and/or adequacy of antiplatelet effect (with in-lab loading) GOAL OF THE STUDY  To evaluate safety and effectiveness of a strategy of 600 mg clopidogrel load given in the cath-lab, at the time of PCI, after diagnostic coronary angiography

5. PCI 600 mg Preload N= 174 438 Patients with - Stable angina or - NSTE ACS undergoing coronary angiography Primary end point: Death, MI*, TVR 2 nd and 3 rd blood sample at 8 and 24 hours 30 days Randomization Angiography Clopidogrel 600 mg given 4-8 hrs before angio N= 218 1 st blood sample before PCI - CK-MB, troponin-I, myoglobin, CRP ARMYDA-5: Study design Clopidogrel 600 mg at the time of PCI N= 220 PCI 600 mg in-lab N= 176 * MI defined as >3 times UNL post-procedural elevation of CK-MB Medical Rx N= 53 CABG N= 35 N= 350

6. ARMYDA-5: STUDY END POINTS Primary end point  30-day incidence of death, MI, target vessel revascularization (MI definition: post-procedural increase of CK-MB >3 times above UNL in patients with normal baseline levels of creatine kinase-MB) Secondary end points Post-procedural increase of markers of myocardial injury above UNL (CK- MB, troponin I, myoglobin) Peak values of CK-MB, troponin I and myoglobin after intervention Occurrence of any vascular/bleeding complications “Point of care” measurement of platelet reactivity at different time points in the two arms

7. Inclusion criteria - Clopidogrel-naïve pts with stable angina or non-STE ACS undergoing PCI Exclusion criteria - Primary PCI - Platelet count <70x10 3 /mL - Pts at high risk of bleeding - Coronary by-pass grafting in the previous 3 months - Therapy with clopidogrel within 10 days ARMYDA-5

8. Age (years) Male sex Systemic hypertension Diabetes mellitus Hypercolesterolemia Current smokers Clinical pattern: non-STE ACS non STEMI Previuos MI Previous PCI Previous CABG Multivessel coronary disease LV ejection fraction 66±9 83% 69% 30% 67% 15% 45% 5% 34% 18% 7% 39% 53±9% 65±10 80% 74% 29% 73% 20% 43% 9% 37% 28% 5% 35% 53±14% 0.34 0.55 0.43 0.44 0.25 0.29 0.89 0.33 0.71 0.03 0.60 0.50 1 Pre-load N=176 In-lab treatment N=174 P ARMYDA-5 Clinical characteristics N = 350 pts

9. Vessel treated: Left main LAD LCx Right coronary PCI for restenosis Lesions B2/C Multivessel Intervention No. of stent/patient Stent diameter (mm) Stent Length (mm) Use of DES Direct Stenting Stent deployment pressure (atm) Duration of stent deployment (sec) Post-dilatation Glycoprotein IIb/IIIa inhibitors - 46% 22% 32% 4% 57% 18% 1.3±0.6 3.04±0.7 16.1±5.4 33% 13.2± 3.4 17±6.1 35% 18% 1% 47% 24% 28% 5% 53% 19% 1.3±0.5 3±0.7 16.2±6.5 35% 34% 13.2± 3.5 16±6.5 29% 19% 0.49 0.96 0.72 0.50 0.84 0.16 0.94 0.69 0.07 0.66 0.86 0.87 0.97 0.25 0.30 0.64 ARMYDA-5 Procedural features Pre-load N=176 In-lab treatment N=174 P

10. ARMYDA-5 trial Composite primary end-point (30-day death, MI, TVR) % 8 11 P=0.56

11. ARMYDA-5 trial Individual components of primary endpoint 8 11 Pre-load In-lab %

12. % of patients with elevation ARMYDA-5 trial Secondary end points Post-procedural CK-MB and Troponin-I elevation above UNL 31 33 P=0.90 39 47 P=0.30 CK-MB Tn-I

13. ARMYDA-5 Trial Secondary end points Post-procedural peak levels of markers of myocardial injury Preload In-lab P= 0.46 P= 0.50 Peak value of CK-MB (ng/ml) Peak value of Tn-I (ng/ml) 0.76±0.9 1.02±1.2 CK-MB Troponin-I 6.4±8 8.1±95

14. ARMYDA-5 Trial Secondary end points Bleeding rates Preload In-lab Patients with bleeding (%) 4 5 0 0

15. 100 120 140 160 180 200 220 240 260 280 300 Platelet Reaction Units (PRU) Pre-load In-lab Study PCI 2 hrs 6 hrs 24 hrs entry ARMYDA-5: Platelet aggregometry* 223±71 241±58 188±74 195±72 187±56 245±89 272±82 245±84 215±91 167±60 P=0.04 P= 0.005 Clopidogrel 600 mg Clopidogrel 600 mg * By VerifyNow TM

16. CONCLUSIONS ARMYDA-5 indicates that 600 mg “in lab” clopidogrel load pre-PCI does not have unfavorable influence on outcome (vs 6 hrs preload). Differences in platelet reactivity by aggregometry (at PCI and at 2 hrs) do not translate into different event rates in the “upstream” vs the in-lab strategy. No bleeding differences and no major bleedings were observed in the 2 arms. The in-lab strategy may obviate the need of preloading before knowing patients’ anatomy: thus, when indicated, in-lab 600 mg clopidogrel administration can be a safe and effective alternative to pretreatment given several hours pre-PCI.

18. 0 5 10 15 20 600 mg300 mg Composite primary end point (%) P=0.041 ARMYDA-2 RESULTS Primary end-point 4% 12% Circulation 2005;111:2099-2106