Principal Investigators: Giuseppe Patti, Vincenzo Pasceri, Giuseppe Colonna

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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 Chairman: Germano Di Sciascio 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

2 ARMYDA-2 RESULTS Primary end-point 30-day Death, MI, TVR (%) P= % 12% 600 mg 300 mg 0 Circulation 2005;111:

3 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

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

5 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

6 ARMYDA-5 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

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

8 ARMYDA-5 Procedural features Pre-load N=176 In-lab treatment N=174 P Vessel treated: Left main LAD LCx Right coronary - 46% 22% 32% 1% 47% 24% 28% PCI for restenosis Lesions B2/C Multivessel Intervention 4% 57% 18% 5% 53% 19% No. of stent/patient Stent diameter (mm) Stent Length (mm) Use of DES 1.3± ± ±5.4 33% 1.3±0.5 3± ±6.5 35% Direct Stenting Stent deployment pressure (atm) Duration of stent deployment (sec) Post-dilatation 33% 13.2± ±6.1 35% 34% 13.2± ±6.5 29% Glycoprotein IIb/IIIa inhibitors 18% 19% 0.64

9 ARMYDA-5 trial Composite primary end-point (30-day death, MI, TVR) % 12 9 P= Pre-load In-lab 3 0

10 ARMYDA-5 trial Individual components of primary endpoint % Death MI TVR Pre-load In-lab

11 ARMYDA-5 trial Secondary end points Post-procedural CK-MB and Troponin-I elevation above UNL P=0.30 % of patients with elevation P= Pre-load In-lab 0 CK-MB Tn-I

12 ARMYDA-5 Trial Secondary end points Post-procedural peak levels of markers of myocardial injury CK-MB Troponin-I Peak value of CK-MB (ng/ml) P= ,8 P= ±8 8.1±95 Peak value of Tn-I (ng/ml) 1,5 1,2 0,9 0,6 0,3 0.76± ± Preload In-lab

13 ARMYDA-5 Trial Secondary end points Bleeding rates Patients with bleeding (%) Preload In-lab 0 Major bleeding Minor bleeding

14 ARMYDA-5: Platelet aggregometry* Clopidogrel 600 mg Platelet Reaction Units (PRU) ±89 223±71 Clopidogrel 600 mg 272±82 241±58 P= ±84 P= ±74 215±91 195±72 187±56 167±60 Pre-load In-lab 100 Study PCI 2 hrs 6 hrs 24 hrs entry * By VerifyNow TM

15 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.