Transcript ARMYDA-4 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study

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
ARMYDA-2 RESULTS
Primary end-point
30-day Death, MI, TVR
15
P=0.041
12%
12
9
6
4%
600 mg
300 mg
3
0
Circulation 2005;111:2099-2106
ADP (5 mol/L)-induced aggregation, %
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
60
40
20
0
Before load
After load Before load After load
600 mg clopidogrel
Kastrati et al. Circulation 2004
ARMYDA-4: Study design
4 -8 Hours pre-PCI
Clopidogrel
600 mg
re-loading ‡
clopidogrel
therapy with

Stable angina
or
 NSTE ACS
undergoing
coronary
angiography
Randomization
464 Patients on
30 days
Medical Rx
N= 62
PCI
“reload” arm
N= 230
Angiography
N= 180
PCI - placebo
arm
Placebo ‡
N= 234
N= 360
CABG
N= 42
1st
blood sample
before PCI
Primary
end point:
Death, MI*,
TVR
N= 180
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
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
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
 Any postprocedural increase of markers of myocardial injury above UNL
(CK-MB, troponin I, myoglobin)
 Mean peak values of CK-MB, troponin I and myoglobin after intervention
 Occurrence of any vascular/hemorragic complications
 “Point of care” evaluation of platelet reactivity at different time points in the
two arms
ARMYDA-4
Clinical Characteristics
N=360 pts
600 mg
Clopidogrel
reload
N=180
Placebo
P
N=180
Age (yrs)
Male sex (%)
Diabetes mellitus (%)
Hypertension (%)
Hypercolesterolemia (%)
Current smokers (%)
65±10
140 (78)
56 (31)
136 (75)
142 (79)
36 (20)
65±10
139 (77)
59 (33)
149 (83)
142 (79)
34 (19)
1
0.99
0.82
0.12
1
0.82
Previous MI (%)
Previous PCI (%)
Previous CABG (%)
Clinical pattern (%)
Non STE ACS
54 (30)
88 (49)
16 (9)
57 (31)
77 (43)
13 (7)
0.82
0.29
0.69
67 (37)
70 (39)
0.83
Multivessel disease (%)
78 (43)
67 (37)
0.83
55±7
180 (100)
171 (95)
55±7
180 (100)
168 (93)
0.28
1
1
LVEF (%)
Aspirin (%)
Statins (%)
ARMYDA – 4 Trial
Procedural features
600 mg
Clopidogrel
reload
N=180
Placebo
Vessel treated (%)
Left main
LAD
LCx
Right coronary
SVG
5 (2)
82 (40)
46 (22)
70 (34)
5 (2)
4 (2)
86 (40)
47 (22)
67 (31)
8 (3)
0.97
0.92
0.92
0.71
0.60
Chronic total occl. (>3 mo.)(%)
18 (10)
10 (5)
0.17
Restenotic lesions (%)
13 (7)
13 (7)
1
Lesion type B2/C (%)
123 (59)
130 (61)
0.92
Multivessel intervention (%)
28 (15)
33 (18)
0.57
Type of intervention (%)
Balloon only
Stent
18 (10)
162 (90)
14 (8)
166 (92)
0.58
0.58
DES (%)
76 (42)
78 (43)
0.91
P
N=180
ARMYDA-4 Trial
Composite primary end-point (30-day death, MI, TVR)
12
P=0.96
%
9
6
3
0
7
8
Placebo
Reload
ARMYDA-4 Trial
Individual events at 30 days
10
%
8
8
7
6
4
2
0
Death
Placebo
MI
TVR
600 mg Clopidogrel
reload
ARMYDA-4 Trial
Secondary end points
Post-procedural elevation of markers of myocardial injury above UNL
P=0.98
50
46
45
P=0.58
% of patients
40
30
27
30
20
10
0
CK-MB
Placebo
Troponin-I
600 mg Clopidogrel
re load
ARMYDA-4 Trial
Secondary end points
Post-PCI peak levels of markers of myocardial injury (CK-MB and Troponin-I)
Troponin-I
CK-MB
8
5.6±7.5
5.3±12
6
4
2
0
CK-MB
Placebo
600 mg
Clopidogrel
reload
Peak value of Tn-I (ng/ml)
Peak value of CK-MB (ng/ml)
P=0.90
P=0.55
1
0,8
0,6
0.39±1.1
0.52±2.2
0.39±0.87
0,4
0,2
0
Placebo
600 mg
Clopidogrel
reload
ARMYDA-4 Trial
Secondary end points
Bleeding rates
6
%
4
4
4
2
0
0
0
Major bleeding
Placebo
Minor bleeding
600 mg Clopidogrel
reload
ARMYDA-4: Platelet aggregometry*
P=0.2
Platelet reaction units (PRU)
240
220
200
211±66
217±66
Clopidogrel
600 mg
208±68
173±69
180
199±64
183±68
177±71
178±62
160
174±65
153±65
Placebo
Further load
166±60
140
146±63
Placebo
120
100
Base
Study
PCI
2 hrs
6 hrs
24 hrs
Drug
* By Accumetrics
CONCLUSIONS
 Results of the ARMYDA-4 trial indicate that a pre-PCI 600 mg
loading dose 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