ARMYDA-5
(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
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
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
ARMYDA-2 RESULTS
Primary end-point
15
P=0.041
12%
12
9
6
4%
600 mg
300 mg
3
0
Circulation 2005;111:2099-2106
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
ARMYDA-5: Study design
30 days
Clopidogrel
600 mg given
4-8 hrs
before angio
- Stableangina
or
- NSTE ACS
undergoing
coronary
angiography
Randomization
438 Patients with
Medical Rx
N= 53
PCI 600 mg
Preload
N= 218
Angiography
Clopidogrel
600 mg at
the time
of PCI
N= 220
N= 350
N= 174
PCI 600 mg
in-lab
CABG
N= 35
1st
blood sample
before PCI
N= 176
2nd and 3rd
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
Primary
end point:
Death, MI*,
TVR
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
ARMYDA-5
Inclusion criteria
- Clopidogrel-naïve pts 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
- Therapy with clopidogrel within 10 days
ARMYDA-5
Clinical characteristics
N = 350 pts
Pre-load
N=176
In-lab treatment
N=174
Age (years)
Male sex
66±9
83%
65±10
80%
0.34
0.55
Systemic hypertension
Diabetes mellitus
Hypercolesterolemia
Current smokers
69%
30%
67%
15%
74%
29%
73%
20%
0.43
0.44
0.25
0.29
Clinical pattern:
• non-STE ACS
• non STEMI
45%
5%
43%
9%
0.89
0.33
Previuos MI
Previous PCI
Previous CABG
34%
18%
7%
37%
28%
5%
0.71
0.03
0.60
39%
53±9%
35%
53±14%
0.50
1
Multivessel coronary disease
LV ejection fraction
P
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%
0.49
0.96
0.72
0.50
PCI for restenosis
Lesions B2/C
Multivessel Intervention
4%
57%
18%
5%
53%
19%
0.84
0.16
0.94
No. of stent/patient
Stent diameter (mm)
Stent Length (mm)
Use of DES
1.3±0.6
3.04±0.7
16.1±5.4
33%
1.3±0.5
3±0.7
16.2±6.5
35%
0.69
0.07
0.66
0.86
Direct Stenting
Stent deployment pressure (atm)
Duration of stent deployment (sec)
Post-dilatation
33%
13.2± 3.4
17±6.1
35%
34%
13.2± 3.5
16±6.5
29%
0.87
0.97
0.25
0.30
18%
19%
0.64
Glycoprotein IIb/IIIa inhibitors
ARMYDA-5 trial
Composite primary end-point (30-day death, MI, TVR)
12
11
P=0.56
%
9
6
3
0
8
Pre-load
In-lab
ARMYDA-5 trial
Individual components of primary endpoint
12
1
1
%
9
8
6
3
0
Death
Pre-load
MI
TVR
In-lab
ARMYDA-5 trial
Secondary end points
Post-procedural CK-MB and Troponin-I elevation above UNL
P=0.30
47
% of patients with elevation
50
P=0.90
40
31
39
33
30
Pre-load
In-lab
20
10
0
CK-MB
Tn-I
ARMYDA-5 Trial
Secondary end points
Post-procedural peak levels of markers of myocardial injury
Troponin-I
CK-MB
8
P= 0.46
1,8
8.1±95
Peak value of Tn-I (ng/ml)
Peak value of CK-MB (ng/ml)
10
6.4±8
6
4
2
P= 0.50
1,5
1.02±1.2
1,2
0.76±0.9
0,9
0,6
0,3
0
0
Preload
In-lab
ARMYDA-5 Trial
Patients with bleeding (%)
Secondary end points
Bleeding rates
6
5
4
4
Preload
In-lab
2
0
0
0
Major bleeding
Minor bleeding
ARMYDA-5: Platelet aggregometry*
Clopidogrel
Platelet Reaction Units (PRU)
600 mg
300
280
260
240
220
200
180
160
140
120
272±82
245±84
245±89
P=0.04
215±91
241±58
P= 0.005
223±71
Pre-load
187±56
In-lab
195±72
188±74
Clopidogrel
167±60
600 mg
100
Study
PCI
2 hrs
6 hrs
24 hrs
entry
* By
VerifyNow TM
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, inlab 600 mg clopidogrel administration can be a safe and
effective alternative to pretreatment given several hours
pre-PCI.
ARMYDA-2 RESULTS
Primary end-point
20
P=0.041
15
12%
10
5
4%
0
600 mg
300 mg
Circulation 2005;111:2099-2106