Name of the speaker: Germano DiSciascio

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ACC 2008 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

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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 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 DAmbrosio,
Annunziata Nusca, Giordano Dicuonzo, Gennaro
Sardella, Bibi NGuyen
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Antiplatet effects of a 600 mg load in pts with
or without chronic clopidogrel Rx
No prior clopidogrel N20
Chronic clopidogrel N20
Plt0.001
100
Plt0.001
80
Plt0.001
ADP (5 ?mol/L)-induced aggregation,
60
40
20
0
Before load
After load
After load
Before load
600 mg clopidogrel
Kastrati et al. Circulation 2004
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ARMYDA - Reload BACKGROUND

• The ARMYDA-2 trial confirmed improved PCI
  outcome with 600 mg clopidogrel loading vs a
  300 mg dose in clopidogrel naïve patients
• 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 while on chronic
  clopidogrel therapy, and to evaluate difference
  in outcome in patients with ACS vs stable angina

5
ARMYDA-Reload Study design
30
days
4
-
8
hrs
PCI Reload N130
Medical Rx (N75)
Stable angina N269
Clopidogrel 600 mg reload N 285
568 Patients on chronic Clopidogrel therapy (gt10
days) with
PCI Placebo N139

• Primary
• endpoint
• Death
• MI
• TVR

Randomization
219 Reload 217 Placebo
PCI 436
Angiography
PCI Reload N89
- NSTE-ACS or
Stable angina
Placebo N283
NSTE-ACS N167
CABG (N57)
PCI Placebo N78

Baseline blood sample
PCI
2 hrs
8 and 24 hrs

• CK-MB
• Troponin-I
• PRU

• PRU

• CK-MB
• Troponin-I
• PRU

• PRU

On top of chronic therapy
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ARMYDA-ReloadSTUDY ENDPOINTS

• Primary endpoint
• 30-day incidence of death, MI, TVR
• MI definition Consensus statement of the
  Joint ESC/ACCF/AHA/WHF Task Force, as a post
  procedural increases of cardiac biomarkers
  (troponin or CK-MB) greater than 3 x 99th
  percentile of the upper reference limit in
  patients with normal baseline levels of CK-MB,
  and as a subsequent elevation of more than
  three-fold in CK-MB from baseline value in
  patients with raised baseline levels of CK-MB
• Secondary endpoints
• Post-procedural increase of markers of myocardial
  injury above UNL (CK-MB, troponin I)
• Occurrence of any vascular/bleeding complications
• Point of care testing of platelet reactivity
  (PRU) at different time points in the reload and
  placebo arms

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Inclusion criteria Patients on chronic (gt 10
days) therapy with clopidogrel (22 of PCI pts
population in the recruiting centers) with stable
angina or non-STE ACS undergoing PCI
Exclusion criteria- Primary PCI- Platelet
count lt70x103/ml- Pts with high risk of
bleeding- Coronary by-pass surgery in the
previous 3 months
ARMYDA-Reload
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ARMYDA-Reload Trial Clinical Characteristics
Stable population N269
600 mg Clopidogrel reload N130
Placebo N139
P
Age (yrs) Male gender () Diabetes mellitus
() Hypertension () Hypercholesterolemia
() Current smokers () Previous MI () Previous
PCI () Previous CABG () Multivessel
disease () LVEF () Aspirin () Statins ()
6610 90 (69) 39 (30) 92 (71) 104 (80) 26
(20) 40 (31) 66 (51) 14 (11) 45 (35) 537 130
(100) 127 (98)
6711 94 (68) 41 (30) 98 (71) 105 (76) 28
(20) 43 (31) 61 (44) 10 (7) 44 (32) 548 139
(100) 130 (94)
0.44 0.88 0.97 0.93 0.46 0.90 0.92 0.31 0.42 0.
70 0.28 - 0.17
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ARMYDA-Reload Trial Clinical Characteristics ACS
population N167
600 mg Clopidogrel reload N89
Placebo N78
P
6410 80 (90) 31 (35) 77 (87) 70 (79) 15
(17) 40 (45) 24 (27) 43 (48) 9 (10) 26
(29) 537 89 (100) 82 (92)
6510 70 (90) 30 (39) 75 (96) 67 (86) 17
(22) 36 (46) 26 (33) 30 (39) 6 (8) 26
(33) 548 78 (100) 70 (90)
0.52 0.82 0.75 0.06 0.31 0.54 0.99 0.47 0.26 0.
78 0.69 0.39 - 0.79
Age (yrs) Male gender () Diabetes mellitus
() Hypertension () Hypercholesterolemia
() Current smokers () Troponin ve
() Previous MI () Previous PCI () Previous
CABG () Multivessel disease () LVEF
() Aspirin () Statins ()
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ARMYDA-Reload Trial Composite primary endpoint
(30-day death, MI, TVR) Overall population N436
P0.70
9

7
11
ARMYDA-Reload Trial Composite primary endpoint
(30-day death, MI, TVR)
Stable
ACS
18
P0.23
P0.035


8
7
4
600 mg Clopidogrel reload
Placebo
12
ARMYDA-Reload Trial Individual components of
primary endpoint
Stable
ACS
18


7
7
4
1
600 mg Clopidogrel reload
Placebo
13
ARMYDA-Reload Secondary endpoints Post-procedura
l elevation of markers of myocardial injury above
UNL
Stable
ACS
P0.31
P0.41
55
P0.016
50
46
45
41
P0.48
25
23
21
of patients
of patients
600 mg Clopidogrel reload
Placebo
14
ARMYDA-Reload Trial Secondary endpoints Bleeding
rates in the overall population
5
5

0
0
600 mg Clopidogrel reload
Placebo
15
ARMYDA-Reload Trial Secondary endpoint Bleeding
rates
Stable
ACS
10
10


2
2
0
0
0
0
N3 N3
N8 N9
600 mg Clopidogrel reload
Placebo
P0.03
16
ARMYDA-Reload Platelet aggregometry
Stable
ACS
P0.046
P0.12
240
240
22785
21862
21057
20362
220
220
Clopidogrel 600 mg
Clopidogrel 600 mg
19263
19359
200
200
21569
18463
18661
20167
20555
20061
17671
180
180
18965
16271
Platelet reaction units (PRU)
Platelet reaction units (PRU)
15963
18079
160
160
17161
16871
17283
15662
13251
140
140
14866
Placebo
120
120
Placebo
12661
100
100
Estimated Study PCI 2
hrs 8 hrs 24 hrs baseline
Drug
Estimated Study PCI 2
hrs 8 hrs 24 hrs baseline
Drug
Placebo
Reload
Using baseline TRAP channel
By VerifyNow TM
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ARMYDA-Reload
Odds Ratios for 30-day MACE
0
1
2
3
5
4
ACS
0.36 (0.29-0.92)
No ACS
1.2 (0.95-1.4)
Diabetes mellitus
0.75 (0.18-4.7)
No diabetes
0.90 (0.38-2.2)
MV intervention
1.2 (0.22-7.8)
No MV intervention
0.80 (0.35-1.9)

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ARMYDA-Reload
EVENT CURVES 30-day MACE and Benefit with
Reload
ACS Placebo
ACS Reload
Stable Angina Placebo
Stable Angina Reload
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CONCLUSIONS

• 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 reloading
  strategy can significantly improve outcome (64
  RR of MACE)
• Serial point of care aggregometry studies show
  platelet reactivity curves consistent with
  clopidogrel status and clinical syndrome, and may
  correlate with outcome
• No major bleeding, and no increased bleeding
  risk are observed in the reload approach vs
  placebo in either stable or ACS patients
• Given the growing number of patients undergoing
  PCI while on clopidogrel, those results may
  influence practice patterns in interventional
  pharmacology

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(No Transcript)
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ARMYDA-Reload Trial Individual events at 30 days
9

6.8
0.5
600 mg Clopidogrel reload
Placebo
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ARMYDA-RELOAD
30-day MACE and Benefit with Reload (600 mg
Clopidogrel)
ACS Placebo
Stable Angina Reload
ACS Reload
Stable Angina Placebo
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ARMYDAReload Trial Procedural features Stable
population N269
600 mg Clopidogrel reload N130
Placebo N139
P
Vessels treated () Left main LAD LCx
RCA SVG Chronic total occl. (gt3
mo.)() Restenotic lesions () Lesion type B2/C
() Multivessel intervention () Type of
intervention () Balloon only Stent
DES () IIb/IIIa inhibitors ()
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)
0.79 0.28 0.77 0.47 0.66 0.25
0.25 0.74 0.99 0.42 0.42 0.30 0.90
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ARMYDAReload Trial Procedural features ACS
population N167
600 mg Clopidogrel reload N89
Placebo N78
P
Vessels treated () Left main LAD LCx
RCA SVG Chronic total occl. (gt3
mo.)() Restenotic lesions () Lesion type B2/C
() Multivessel intervention () Type of
intervention () Balloon only Stent
DES () IIb/IIIa inhibitors ()
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)
0.69 0.90 0.99 0.98 0.83 0.86 0.46 0.75
0.91 0.91 0.77 0.88
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ARMYDA-Reload Platelet aggregometry
Overall population
P0.01
240
21565
21166
220
Clopidogrel 600 mg
200
19066
20868
17869
19958
17070
180
18565
Platelet reaction units (PRU)
14865
160
17261
16258
140
14261
Placebo
120
100
Estimated Study PCI
2 hrs 8 hrs 24 hrs
baseline Drug
By VerifyNow TM
Using baseline TRAP channel