armyda-5 (antiplatelet therapy for reduction of myocardial damage during angioplasty) study...
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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”
Principal Investigator: Giuseppe Patti
Investigators: Vincenzo Pasceri, Giuseppe Colonna, Antonio Montinaro, Leonardo Lassandro Pepe, Francesco Ciccirillo, Laura Gatto, Fabio Mangiacapra, Antonio Tondo, Andrea D’Ambrosio, Annunziata Nusca, Giordano Dicuonzo, Gennaro Sardella, Bibi NGuyen
Chairman: Germano Di Sciascio
3 0- d
a y D
eath
, MI,
TV
R (
%)
ARMYDA-2 RESULTSPrimary end-point
Circulation 2005;111:2099-2106
P=0.041
4%
12%
0
3
6
9
12
15
600 mg
300 mg
ARMYDA-5 PRELOAD: 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
PCI 600 mgPreloadN= 204
536 Patients with
- Stable angina or
- NSTE ACS
undergoing coronary angiography
Primary end point: cardiac death, MI, TVR
30 days
Angiography
Clopidogrel600 mg given
4-8 hrs before angio
N= 267
ARMYDA-5 PRELOAD: Study designARMYDA-5 PRELOAD: Study design
Clopidogrel600 mg at the time of PCI
N= 269
PCI 600 mg in-lab
N= 205
Medical RxN= 72
CABGN= 55
N= 409
Ran
dom
izat
ion
CK-MB Troponin-I PRU
1st blood sample
Baseline
2nd, 3rd, 4th and 5th blood samples
At the time of PCI
2 hrs after PCI
8 and 24 hrsafter PCI
PRU CK-MB Troponin-I PRU
PRU
ARMYDA-5: STUDY END POINTS
Primary end point
30-day incidence of cardiac death, MI, target vessel revascularization
(MI definition: post-procedural increase of CK-MB >3 times above UNL in patients with normalbaseline levels of CK-MB; subsequent elevation 50% the baseline value of CK-MB in patients with ACSand raised baseline CK-MB levels)
Secondary end points
Post-procedural increase of markers of myocardial injury above UNL (CK-MB, troponin I, myoglobin)
Occurrence of any vascular/bleeding complications (Safety secondary end point)
“Point of care” measurement of platelet reactivity at different time points in the two arms
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 PRELOAD
Age (years)Male sex
Systemic hypertension Diabetes mellitusHypercolesterolemia Current smokers
Clinical pattern:• Non-STE ACS• Troponin positive
Previuos MIPrevious PCIPrevious CABG
Multivessel coronary diseaseLV ejection fraction
66±982%
74% 33% 69% 21%
43%45%
34%24%9%
43%55±9%
65±1081%
75%36%75%22%
36%47%
33%32%6%
36%56±8%
0.290.82
0.890.560.210.92
0.180.59
0.810.100.45
0.180.22
Pre-loadN=204
In-lab treatmentN=205
P
ARMYDA-5 PRELOAD Clinical characteristics
N = 409 pts
Vessel treated: Left main LAD LCx Right coronary SVG
PCI for restenosisLesions B2/CMultivessel Intervention
No. of stent/patientStent diameter (mm)Stent Length (mm)Use of DES
Direct StentingStent deployment pressure (atm)Duration of stent deployment (sec)Post-dilatation
Glycoprotein IIb/IIIa inhibitors
1%44%25%29%1%
10%
53%15%
1.14±0.73.15±0.6
20±935%
35%14.8± 222±1234%
19%
2%43%26%28%1%
11%54%16%
1.12±0.63.14±0.5
19±1039%
35%14.9± 2.1
20±1134%
20%
0.690.960.970.810.69
0.990.960.91
0.750.84 0.280.50
0.950.620.080.97
0.82
ARMYDA-5 PRELOADProcedural features
Pre-loadN=204
In-lab treatmentN=205
P
0
4
8
12
16
20
In-lab load Preload
P=0.72
5 10 15 20 25 30
Days after PCI
Cu
mu
lati
ve in
cid
ence
of
MA
CE
(%
)
ARMYDA-5 PRELOAD: Primary end point
Adverse events at 30 days(Clopidogrel in-lab load vs preload)
0
4
8
12
16
20
Death MI TVR
In-lab load
Preload
% o
f p
atie
nts
9.39.3 8.88.8
ARMYDA-5 PRELOADIndividual components of the primary end point at 30 days
0.50.5 0 0 0.50.5 0 0
Cr e
a ti n
e k
i na s
e -M
B (
%) P=0.83
Tro
po n
i n- I
(%
)
P=0.85
ARMYDA-5 PRELOAD: Secondary end point
0
10
20
30
40
In-lab load Preload0
15
30
45
60
75
In-lab load Preload
1-3 times
>3 times
1-3 times
>3 times
0
4
8
12
16
20
Majorbleeding
In-lab load
Preload
% o
f p
atie
nts
% o
f p
atie
nts
ARMYDA-5 PRELOAD: Safety secondary end point
0 0
7.87.8
5.4 5.4
P=0.42
Minorbleeding
0 0
In-lab load Preload
140
165
190
215
240
265
290
315
Study entry PCI 2 hrs 8 hrs 24 hrs
P2Y
12 r
eact
ion
Un
its
(PR
U)
P=0.043
0
P=0.01
ARMYDA-5 PRELOAD: Platelet reactivity curves
Clopidogrel6
00 mg
Clopidogrel
600 mg
276±63
250±75
245±72
212±72209±70 206±73 182±72
224±74227±71
174±74
CONCLUSIONS
ARMYDA-5 PRELOAD 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.