1. ARMYDA-4
(Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study
Germano Di Sciascio, MD, FACC, FESC Professor & Chairman of Cardiology Director, Department of Cardiovascular Sciences Institute Campus Biomedico University of Rome Rome, Italy  

2. TCT 2007 – Disclosure Slide 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

3. in patients on chronic therapy - “ARMYDA-Reload”
ARMYDA-4 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study
Prospective, multicenter, randomized, double blind trial investigating influence on PCI outcome of additional 600 mg clopidogrel load
in patients on chronic therapy - “ARMYDA-Reload”
Chairman: Germano Di Sciascio
Principal Investigators: Giuseppe Patti, Vincenzo Pasceri, Giuseppe Colonna
Investigators: Antonio Montinaro, Leonardo Lassandro Pepe, Antonio Tondo, Laura Gatto, Fabio Mangiacapra, Francesco Ciccirillo, Andrea D’Ambrosio, Annunziata Nusca, Giordano Dicuonzo, Gennaro Sardella, Bibi NGuyen 3

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

5. Antiplatet effects of a 600 mg load in pts
with or without chronic clopidogrel Rx
No prior clopidogrel
N=20
Chronic clopidogrel
N=20
P<0.001
100
P<0.001 80
P<0.001
ADP (5 mol/L)-induced aggregation, % 60 40 20
Before load
After load
Before load
After load
600 mg clopidogrel
Kastrati et al. Circulation 2004

6. ARMYDA-4: Study design N= 360 N= 230 N= 180 N= 180 N= 234
Hours pre-PCI 30
days
Medical Rx
N= 62
Clopidogrel
600 mg
re-loading ‡
N= 230
N= 360
464 Patients on
clopidogrel
therapy with
PCI
“reload” arm
N= 180
Primary
end point:
Death, MI*,
TVR ü
Stable
angina or
Angiography
Randomization ü
NSTE ACS
PCI - placebo arm
N= 180 ü
undergoing
Placebo ‡
N= 234
coronary
angiography
CABG
N= 42
1st
blood sample
before PCI
2nd and 3rd
blood sample at
8 and 24 hours
- CK-MB, troponin-I, myoglobin, CRP
‡ On top of chronic therapy
* MI = >3 times UNL CK-MB

7. ARMYDA-4: STUDY ENDPOINTS
Primary endpoint
30-day incidence of death, MI, TVR
(MI definition: post-procedural increase of CK-MB >3 times above UNL in patients with normal baseline levels of creatine kinase-MB)
Secondary endpoints
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” evaluation of platelet reactivity at different time points in the two arms

8. ARMYDA-4
Inclusion criteria - Pts on chronic therapy with clopidogrel (> 10 days) with stable angina or non-STE ACS undergoing PCI Exclusion criteria - Primary PCI - Platelet count <70x103/ml - Pts at high risk of bleeding - Coronary by-pass grafting in the previous 3 months

9. Clinical Characteristics
ARMYDA-4
Clinical Characteristics
N=360 pts
600 mg
Clopidogrel
reload
N=180
Placebo
N=180 P
Age (yrs)
Male sex (%)
Diabetes mellitus (%)
Hypertension (%)
Hypercolesterolemia (%)
Current smokers (%)
Previous MI (%)
Previous PCI (%)
Previous CABG (%)
Clinical pattern (%)
Non STE ACS
Non STEMI
Multivessel disease (%)
LVEF (%)
Aspirin (%)
Statins (%)
65±10
140 (78)
56 (31)
136 (75)
142 (79)
36 (20)
54 (30)
88 (49)
16 (9)
67 (37)
22 (12)
78 (43)
55±7
180 (100)
171 (95)
65±10
139 (77)
59 (33)
149 (83)
142 (79)
34 (19)
57 (31)
77 (43)
13 (7)
70 (39)
14 (8)
67 (37)
55±7
180 (100)
168 (93) 1
0.99
0.82
0.12
0.29
0.69
0.83
0.51
0.28

10. ARMYDA – 4 Trial Procedural features
600 mg
Clopidogrel
reload
N=180
Placebo
N=180 P
Vessel treated (%)
Left main
LAD
LCx
Right coronary
SVG
Chronic total occl. (>3 mo.) (%)
Restenotic lesions (%)
Lesion type B2/C (%)
Multivessel intervention (%)
Type of intervention (%)
Balloon only
Stent
DES (%)
IIb/IIIa inhibitors
5 (2)
82 (40)
46 (22)
70 (34)
18 (10)
13 (7)
123 (59)
28 (15)
162 (90)
76 (42)
20 (11)
4 (2)
86 (40)
47 (22)
67 (31)
8 (3)
10 (5)
13 (7)
130 (61)
33 (18)
14 (8)
166 (92)
78 (43)
0.97
0.92
0.71
0.60
0.17 1
0.57
0.58
0.91
0.45

11. Composite primary end-point (30-day death, MI, TVR)
ARMYDA-4 Trial
Composite primary end-point (30-day death, MI, TVR)
P=0.96 % 8 7

12. Individual components of composite primary endpoint
ARMYDA-4 Trial
Individual components of composite primary endpoint % 8 7
600 mg Clopidogrel reload
Placebo

13. Post-procedural elevation of markers of myocardial injury above UNL
ARMYDA-4 Trial
Secondary end points
Post-procedural elevation of markers of myocardial injury above UNL
P=0.98 46 45
P=0.58 30 27
% of patients
600 mg Clopidogrel
re load
Placebo

14. ARMYDA-4 Trial Secondary end points
Post-PCI peak levels of markers of myocardial injury (CK-MB and Troponin-I)
CK-MB
Troponin-I
P=0.55
P=0.90
5.6±7.5
5.3±12
0.52±2.2
0.39±1.1
Peak value of Tn-I (ng/ml)
Peak value of CK-MB (ng/ml)
600 mg Clopidogrel
re load
Placebo

15. ARMYDA-4 Trial Secondary end points Bleeding rates % 4 4
600 mg Clopidogrel
reload
Placebo

16. ARMYDA-4: Platelet aggregometry*
240
211±66
217±66
220
Clopidogrel
600 mg
200
208±68
183±68
199±64
173±69
177±71
Placebo
Reload
180
178±62
Platelet reaction units (PRU)
174±65
153±65
160
166±60
140
146±63
120
Placebo
100
Estimated Study PCI hrs hrs hrs
baseline ** Drug
** Using baseline TRAP channel
* By VerifyNow TM

17. CONCLUSIONS
The ARMYDA-4 trial indicates that a pre-PCI 600 mg loading does not confer additional clinical benefit in patients already receiving chronic therapy with clopidogrel
Point of care aggregometry testing shows no significant differences in platelet reactivity in the 2 arms
No increased bleeding risk is observed in the “reload” approach
Patients on chronic clopidogrel therapy can safely undergo PCI without need of further reload

18. BACKGROUND
Several studies have demonstrated beneficial clinical effects of a 600 mg clopidogrel loading dose in patients undergoing percutaneous coronary intervention (PCI).
Laboratory evidence suggests that an additional pre-PCI 600 mg loading further decreases platelet aggregation in patients already on chronic treatment with clopidogrel. However, there are no clinical data on the safety and efficacy of this strategy.

19. Antiplatet effects of a 600 mg load on chronic clopidogrel Rx
No prior clopidogrel
N=20
Chronic clopidogrel
N=20
P<0.001
100
P<0.001 80
P<0.001
ADP (5 mol/L)-induced aggregation, % 60 40 20
Before load
After load
Before load
After load
600 mg clopidogrel
Kastrati et al. Circulation 2004