Name of the speaker: Germano DiSciascio I have the following potential conflicts of interest to...
-
Upload
barnaby-floyd -
Category
Documents
-
view
212 -
download
0
Transcript of Name of the speaker: Germano DiSciascio I have the following potential conflicts of interest to...
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
ACC 2008 – Disclosure Slide
ARMYDA (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study group
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
Antiplatet effects of a 600 mg load in pts Antiplatet effects of a 600 mg load in pts with or without chronic clopidogrel Rx with or without 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
ARMYDA - Reload: BACKGROUND
The ARMYDA-2 trial confirmed improved PCI outcome in patients pretreated (mean 6 hrs) with 600 mg clopidogrel loading , vs a 300 mg dose
In patients already receiving clopidogrel, concerns about bleeding (with reloading), and/or adequacy of antiplatelet effect (without additional loading)
GOAL OF THE STUDY
To evaluate safety and effectiveness of a strategy of 600 mg clopidogrel reload in patients undergoing PCI on chronic clopidogrel therapy, and to evaluate difference in outcome in patients with ACS vs stable angina
Stable angina N=269
568 Patients on
chronic Clopidogrel
therapy (>10 days)
with
Primary endpoint:- Death- MI- TVR
4 - 8 hrs 30 days
Ran
dom
izat
ion
Placebo ‡N=283
Angiography
Medical Rx (N=75)
CABG (N=57)
Clopidogrel600 mg reload ‡N= 285
NSTE ACSN=167
- NSTE ACS or - Stable angina
Creatine kinase-MB Troponin-I PRU
1st blood sample
Baseline
2nd, 3rd and 4th blood samples
At the time of PCI
2 hrs after PCI
8 and 24 hrsafter PCI
PRU Creatine kinase-MB Troponin-I PRU
PRU
ARMYDA-RELOAD: Study design
PCI ReloadN=130
PCI PlaceboN=139
PCI ReloadN=89
PCI PlaceboN=78
‡ On top of chronic therapy
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)
Occurrence of any vascular/bleeding complications “Point of care” evaluation of platelet reactivity at different time points in the
two arms
Inclusion criteria
Pts on chronic therapy with clopidogrel (> 10 days) with stable angina or non-STE ACS undergoing PCI(22% of PCI patient population in the recruiting centers)
Exclusion criteria
- Primary PCI- Platelet count <70x103/ml- Pts with high risk of bleeding- Coronary by-pass surgery in the previous 3 months
ARMYDA-RELOADARMYDA-RELOAD
Age (yrs)Male sex (%) Diabetes mellitus (%)Hypertension (%)Hypercholesterolemia (%)Current smokers (%)
Previous MI (%)Previous PCI (%)Previous CABG (%) Multivessel disease (%)
LVEF (%)Aspirin (%)Statins (%)
600 mgClopidogrel
reload N=130
Placebo
N=139
P
ARMYDA-RELOAD TrialClinical Characteristics
Stable populationN=269
66±1090 (69) 39 (30)92 (71)
104 (80)26 (20)
40 (31)66 (51)14 (11)
45 (35)
53±7130 (100)127 (98)
67±1194 (68) 41 (30)98 (71)
105 (76)28 (20)
43 (31)61 (44)10 (7)
44 (32)
54±8139 (100)130 (94)
0.440.88 0.970.930.460.90
0.920.310.42
0.70
0.28-
0.17
Age (yrs)Male sex (%) Diabetes mellitus (%)Hypertension (%)Hypercholesterolemia (%)Current smokers (%)
Troponin +ve (%)
Previous MI (%)Previous PCI (%)Previous CABG (%) Multivessel disease (%)
LVEF (%)Aspirin (%)Statins (%)
600 mgClopidogrel
reload N=89
Placebo
N=78
P
ARMYDA-RELOAD TrialClinical Characteristics
ACS populationN=167
64±1080 (90) 31 (35)77 (87)70 (79)15 (17)
40 (45)
24 (27)43 (48)9 (10)
26 (29)
53±789 (100)82 (92)
65±1070 (90) 30 (39)75 (96)67 (86)17 (22)
36 (46)
26 (33)30 (39)
6 (8)
26 (33)
54±878 (100)70 (90)
0.520.82 0.750.060.310.54
0.99
0.470.260.78
0.69
0.39-
0.79
P
Vessel treated (%) Left main LAD LCx RCA SVG
Chronic total occl. (>3 mo.)(%)
Restenotic lesions (%)
Lesion type B2/C (%)
Multivessel intervention (%)
Type of intervention (%) Balloon only Stent DES (%)
IIb/IIIa inhibitors (%)
600 mgClopidogrel
reload N=130
Placebo
N=139
ARMYDA–RELOAD Trial Procedural features Stable population
N=269
4 (2)63 (39) 38 (24) 54 (34)
2 (1)
18 (14)
18 (14)
70 (54)
30 (23)
15 (12) 115 (88)
70 (54)
7 (5)
4 (2)78 (46) 37 (22) 50 (29)2 (1)
12 (9)
12 (9)
71 (51)
31 (22)
11 (8) 128 (92)
65 (47)
6 (4)
0.790.28 0.77 0.470.66
0.25
0.25
0.74
0.99
0.42 0.42
0.30
0.90
P
Vessel treated (%) Left main LAD LCx RCA SVG
Chronic total occl. (>3 mo.)(%)
Restenotic lesions (%)
Lesion type B2/C (%)
Multivessel intervention (%)
Type of intervention (%) Balloon only Stent DES (%)
IIb/IIIa inhibitors (%)
600 mgClopidogrel
reload N=89
Placebo
N=78
ARMYDA–RELOAD Trial Procedural features
ACS population N=167
2 (2)41 (42) 20 (20) 29 (29)
7 (7)
-
4 (5)
51 (57)
10 (11)
5 (6) 84 (94)
20 (22)
18 (20)
2 (2)37 (42) 17 (19) 25 (28)8 (9)
-
3 (4)
50 (64)
11 (14)
5 (6) 73 (94)
20 (26)
16 (21)
0.690.90 0.99 0.980.83
0.86
0.46
0.75
0.91 0.91
0.77
0.88
0
3
6
9
12
Placebo
Reload
ARMYDA-RELOAD TrialComposite primary endpoint (30-day death, MI, TVR)
Overall population N=436
% 9
7
P=0.70
0
5
10
15
20
ARMYDA-RELOAD TrialComposite primary endpoint (30-day death, MI, TVR)
%
4
8
P=0.23
0
5
10
15
20
%
600 mg Clopidogrel reloadPlacebo
Stable ACS
P=0.03518
7
ARMYDA-RELOAD TrialIndividual events at 30 days
600 mg Clopidogrel reloadPlacebo
0
2
4
6
8
10
Death MI TVR
6.8
9
%
0.5
ARMYDA-RELOAD TrialIndividual components of primary endpoint
600 mg Clopidogrel reloadPlacebo
0
5
10
15
20
Death MI TVR
4
7
%
0
5
10
15
20
Death MI TVR
18
7
%
Stable ACS
1
0 1 2
Odds Ratios for 30-day MACE
ACS
No ACS
Diabetes mellitus
3 4 5
No diabetes
MV intervention
0.36 (0.29-0.92)
1.2 (0.95-1.4)
0.75 (0.18-4.7)
0.90 (0.38-2.2)
1.2 (0.22-7.8)
No MV intervention 0.80 (0.35-1.9)
ARMYDA-RELOAD
ARMYDA-RELOAD Secondary endpoint
Any post-procedural elevation of markers of myocardial injury above UNL
% o
f p
atie
nts
600 mg Clopidogrel reloadPlacebo
0
10
20
30
40
50
60
CK-MB Troponin-I
25
% o
f p
atie
nts
0
10
20
30
40
50
60
CK-MB Troponin-I
41
23
55
46
P=0.016
P=0.31
21
50
45
P=0.48
P=0.41
Stable ACS
ARMYDA-RELOAD Trial Secondary endpoint:
Bleeding rates in the overall population
0
2
4
6
Major bleeding Minor bleeding
600 mg Clopidogrel reloadPlacebo
%
5 5
0 0
ARMYDA-RELOAD Trial Secondary endpoint:
Bleeding rates
0
2
4
6
Major bleeding Minor bleeding
600 mg Clopidogrel reloadPlacebo
%
2 2
0 0
0
3
6
9
12
Major bleeding Minor bleeding
%10 10
0 0
Stable ACS
N=3 N=3 N=8 N=9
EVENT CURVES
30-day MACE and Benefit with Reload
ACS Placebo
Stable Angina Reload
ACS Reload
Stable Angina Placebo
ARMYDA-RELOAD
0
4
8
12
16
20
5 10 15 20 25 30
Days after randomization
Dea
th/M
I/Rep
eat
reva
scu
lari
zati
on
(%
)
P=0.035 (ACS Placebo vs ACS Reload)
211±66
162±58
215±65
185±65
178±69
148±65
208±68
170±70199±58
190±66
172±61
142±61
Estimated Study PCI 2 hrs 8 hrs 24 hrs
baseline ** Drug
100
120
140
160
180
200
220
240
Pla
tele
t re
acti
on u
nits
(P
RU
)ARMYDA-RELOAD: Platelet aggregometry* Overall population
P=0.01
* By VerifyNow TM
Placebo
Clopidogrel
600 mg
Placebo
Reload
** Using baseline TRAP channel
ARMYDA-RELOAD: Platelet aggregometry*
* By VerifyNow TM
Placebo Reload
203±62
156±62
210±57
193±59184±63
159±63
201±67
162±71
200±61
189±65
168±71
148±66
Estimated Study PCI 2 hrs 8 hrs 24 hrs
baseline ** Drug
100
120
140
160
180
200
220
240
Pla
tele
t re
acti
on u
nit
s (P
RU
) P=0.12
Placebo
Clopidogrel
600 mg
** Using baseline TRAP channel
Stable ACS
218±62
171±61
227±85
180±79
172±83
126±61
215±69
176±71205±55
192±63
186±61
132±51
Estimated Study PCI 2 hrs 8 hrs 24 hrs
baseline ** Drug
100
120
140
160
180
200
220
240
Pla
tele
t re
acti
on u
nit
s (P
RU
) P=0.046
Placebo
Clopidogrel
600 mg
The ARMYDA-Reload trial indicates that a significant proportion of patients undergoing PCI are on chronic clopidogrel therapy
Patients with stable angina who are already taking clopidogrel can safely undergo PCI without need of further reload
In patients with ACS, a 600 mg reload strategy can significantly improve outcome
Point of care aggregometry testing shows differences in platelet reactivity consistent with clopidogrel status and clinical syndrome
No major bleeding, and no increased bleeding risk are observed in the “reload” approach in either stable or ACS patients
Given the growing number of patients on clopidogrel undergoing PCI, those results may influence practice patterns in interventional pharmacology
CONCLUSIONS