1. 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 Investigator: Giuseppe Patti Investigators: Vincenzo Pasceri, Giuseppe Colonna, 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

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

3. ARMYDA-5 PRELOAD: 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

4. PCI 600 mg Preload N= 204 536 Patients with - Stable angina or - NSTE ACS undergoing coronary angiography Primary end point: cardiac death, MI, TVR 30 days Angiography Clopidogrel 600 mg given 4-8 hrs before angio N= 267 ARMYDA-5 PRELOAD: Study design Clopidogrel 600 mg at the time of PCI N= 269 PCI 600 mg in-lab N= 205 Medical Rx N= 72 CABG N= 55 N= 409 Randomization  CK-MB  Troponin-I  PRU 1 st blood sample Baseline 2 nd, 3 rd, 4 th and 5 th blood samples At the time of PCI 2 hrs after PCI 8 and 24 hrs after PCI  PRU  CK-MB  Troponin-I  PRU

5. ARMYDA-5: STUDY END POINTS Primary end point  30-day incidence of cardiac death, MI, target vessel revascularization (MI definition: post-procedural increase of CK-MB >3 times above UNL in patients with normal baseline levels of CK-MB; subsequent elevation 50% the baseline value of CK-MB in patients with ACS and raised baseline CK-MB levels) Secondary end points Post-procedural increase of markers of myocardial injury above UNL (CK- MB, troponin I, myoglobin) Occurrence of any vascular/bleeding complications (Safety secondary end point) “Point of care” measurement of platelet reactivity at different time points in the two arms

6. 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 PRELOAD

7. Age (years) Male sex Systemic hypertension Diabetes mellitus Hypercolesterolemia Current smokers Clinical pattern: Non-STE ACS Troponin positive Previuos MI Previous PCI Previous CABG Multivessel coronary disease LV ejection fraction 66±9 82% 74% 33% 69% 21% 43% 45% 34% 24% 9% 43% 55±9% 65±10 81% 75% 36% 75% 22% 36% 47% 33% 32% 6% 36% 56±8% 0.29 0.82 0.89 0.56 0.21 0.92 0.18 0.59 0.81 0.10 0.45 0.18 0.22 Pre-load N=204 In-lab treatment N=205 P ARMYDA-5 PRELOAD Clinical characteristics N = 409 pts

8. Vessel treated: Left main LAD LCx Right coronary SVG 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 1% 44% 25% 29% 1% 10% 53% 15% 1.14±0.7 3.15±0.6 20±9 35% 14.8± 2 22±12 34% 19% 2% 43% 26% 28% 1% 11% 54% 16% 1.12±0.6 3.14±0.5 19±10 39% 35% 14.9± 2.1 20±11 34% 20% 0.69 0.96 0.97 0.81 0.69 0.99 0.96 0.91 0.75 0.84 0.28 0.50 0.95 0.62 0.08 0.97 0.82 ARMYDA-5 PRELOAD Procedural features Pre-load N=204 In-lab treatment N=205 P

9. 0 4 8 12 16 20 In-lab loadPreload P=0.72 5 1015202530 Days after PCI Cumulative incidence of MACE (%) ARMYDA-5 PRELOAD: Primary end point Adverse events at 30 days (Clopidogrel in-lab load vs preload)

10. 0 4 8 12 16 20 DeathMITVR In-lab load Preload % of patients 9.3 9.3 8.8 8.8 ARMYDA-5 PRELOAD Individual components of the primary end point at 30 days 0.5 0.5 0 0

11. Creatine kinase-MB (%) P=0.83 Troponin-I (%) P=0.85 ARMYDA-5 PRELOAD: Secondary end point 0 10 20 30 40 In-lab loadPreload 0 15 30 45 60 75 In-lab loadPreload 1-3 times >3 times 1-3 times >3 times

12. 0 4 8 12 16 20 Major bleeding In-lab load Preload % of patients ARMYDA-5 PRELOAD: Safety secondary end point 0 7.8 7.8 5.4 5.4 P=0.42 Minor bleeding 0

13. In-lab load Preload 140 165 190 215 240 265 290 315 Study entryPCI2 hrs8 hrs24 hrs P2Y12 reaction Units (PRU) P=0.043 0 P=0.01 ARMYDA-5 PRELOAD: Platelet reactivity curves Clopidogre l600 mg Clopidogrel 600 mg 276±63 250±75 245±72 212±72 209±70 206±73 182±72 224±74 227±71 174±74

14. CONCLUSIONS ARMYDA-5 PRELOAD 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.