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.