Post on 03-Jan-2016
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”
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
Chairman: Germano Di Sciascio
(%)
ARMYDA-2 RESULTSPrimary end-point30-day Death, MI, TVR
Circulation 2005;111:2099-2106
P=0.041
4%
12%
0
3
6
9
12
15
600 mg
300 mg
Antiplatet effects of a 600 mg load on chronic clopidogrel Rx Antiplatet effects of a 600 mg load on chronic clopidogrel Rx
0
20
40
60
80
100
AD
P (
5 A
DP
(5 m
ol/L
)-in
du
ced
agg
rega
tion
, %m
ol/L
)-in
du
ced
agg
rega
tion
, %
600 mg clopidogrel600 mg clopidogrelBefore loadBefore load Before loadBefore loadAfter loadAfter load After loadAfter load
No prior clopidogrelNo prior clopidogrel N=20N=20
Chronic clopidogrelChronic clopidogrel N=20N=20
P<0.001P<0.001
P<0.001P<0.001
P<0.001P<0.001
Kastrati et al. Circulation 2004Kastrati et al. Circulation 2004
PCI “reload” arm
N= 180
464 Patients on clopidogrel
therapy with Stable angina
or NSTE ACS
undergoing coronary angiography
Primary end point: Death, MI*, TVR
2nd and 3rd blood sample at 8 and 24 hours
30 days
Ran
dom
izat
ion
Angiography
Clopidogrel600 mg
re-loading ‡ N= 230
1st blood samplebefore PCI
- CK-MB, troponin-I, myoglobin, CRP
ARMYDA-4: Study designARMYDA-4: Study design
Placebo ‡N= 234
PCI - placebo arm
N= 180
4 -8 Hours pre-PCI
* MI = >3 times UNL CK-MB‡ On top of chronic therapy
Medical RxN= 62
CABGN= 42
N= 360
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
ARMYDA-4ARMYDA-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
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
Age (yrs)Male sex (%) Diabetes mellitus (%)Hypertension (%)Hypercolesterolemia (%)Current smokers (%)
Previous MI (%)Previous PCI (%)Previous CABG (%)Clinical pattern (%) Non STE ACS Multivessel disease (%)
LVEF (%)Aspirin (%)Statins (%)
600 mgClopidogrel
reload N=180
Placebo
N=180
P
65±10140 (78) 56 (31)
136 (75)142 (79)36 (20)
54 (30)88 (49)16 (9)
67 (37)
78 (43)
55±7180 (100)171 (95)
65±10139 (77) 59 (33)
149 (83)142 (79)34 (19)
57 (31)77 (43)13 (7)
70 (39)
67 (37)
55±7180 (100)168 (93)
10.99 0.820.12
10.82
0.820.290.69
0.83
0.83
0.2811
ARMYDA-4Clinical Characteristics
N=360 pts
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 (%)
5 (2)82 (40) 46 (22) 70 (34)
5 (2)
18 (10)
13 (7)
123 (59)
28 (15)
18 (10) 162 (90)
76 (42)
4 (2)86 (40) 47 (22) 67 (31)
8 (3)
10 (5)
13 (7)
130 (61)
33 (18)
14 (8) 166 (92)
78 (43)
0.970.92 0.92 0.710.60
0.17
1
0.92
0.57
0.58 0.58
0.91
600 mgClopidogrel
reload N=180
Placebo
N=180
ARMYDA – 4 Trial Procedural features
0
3
6
9
12
Placebo
Reload
ARMYDA-4 TrialComposite primary end-point (30-day death, MI, TVR)
%
78
P=0.96
ARMYDA-4 TrialIndividual events at 30 days
600 mg Clopidogrel reloadPlacebo
0
2
4
6
8
10
Death MI TVR
7
8%
ARMYDA-4 Trial Secondary end points
Post-procedural elevation of markers of myocardial injury above UNL%
of
pat
ien
ts
600 mg Clopidogrel
re loadPlacebo
0
10
20
30
40
50
CK-MB Troponin-I
P=0.98
P=0.584546
2730
ARMYDA-4 Trial Secondary end points
Post-PCI peak levels of markers of myocardial injury (CK-MB and Troponin-I)
600 mg Clopidogrel
reloadPlacebo
Pea
k v
alu
e o
f C
K-M
B (
ng
/ml)
Pea
k v
alu
e o
f T
n-I
(n
g/m
l)
5.6±7.5 5.3±12
0.52±2.20.39±0.87
0
2
4
6
8
CK-MB
P=0.90
CK-MB
0
0,2
0,4
0,6
0,8
1 P=0.55
600 mg Clopidogrel
reloadPlacebo
Troponin-I
0.39±1.1
ARMYDA-4 Trial Secondary end points
Bleeding rates
0
2
4
6
Major bleeding Minor bleeding
600 mg Clopidogrelreload
Placebo
% 4 4
0 0
211±66
166±60
217±66
183±68177±71
153±65
208±68
173±69199±64
178±62174±65
146±63
Base Study PCI 2 hrs 6 hrs 24 hrs
Drug
100
120
140
160
180
200
220
240
Pla
tele
t re
acti
on u
nits
(P
RU
)ARMYDA-4: Platelet aggregometry*
P=0.2
* By Accumetrics
Placebo
Clopidogrel
600 mg
Placebo
Further load
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
CONCLUSIONS
• 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.
BACKGROUND