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Presenter Disclosure Information
Eric Bonnefoy
The following relationships exist related to this
presentation
Research grants Merck Co, Iroko
Lab Important (provided tirofiban free of
charge for the AGIR2 study) Speakers
honoraria Eli Lilly Modest
24
Comparison of Pre-hospital or Cath lab
Administration of High Dose Tirofiban in
Patients Undergoing Primary AngioplastyThe
AGIR2 Study
Eric Bonnefoy on behalf of AGIR2 investigators
and RESCUe and RESURCOR networksHospices Civils
de Lyon, France
25
Background

• In patients undergoing primary PCI,
• GPIIbIIIa inhibitors improve angiographic and
  clinical outcome
• Early administration of GPIIbIIIa inhibitors
  improved pre-procedural epicardial flow
• On top of a high loading dose of clopidogrel,
  early high-dose tirofiban improved ST segment
  resolution and clinical outcome
• The extent of the benefit of pre-hospital
  tirofiban as compared with cath lab tirofiban on
  top of a high loading dose of clopidogrel is
  unknown

26
Rationale

• If widely applied, pre-hospital initiation of
  GPIIbIIIa inhibitors would
• require a huge transfer of financial burden to
  emergency units
• increase the complexity of pre-hospital protocols
  in patients with acute ST segment elevation
  coronary syndrome (STEMI)
• Such a consequence would be particularly true in
  large emergency medicine-cardiology networks

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STEMI undergoing primary PCI
Patientcall
600 mg clopidogrel 250 mg aspirin UFH 60 U/kg
inf
MICU
Medical Dispatcher
Randomize Open Label
Pre-hospital
Tirofiban25/0.15
MICUtransportation
Cath lab
Tirofiban25/0.15
Angiography
Angiography
28
Annecy
Lyon
Mont Blanc
11 cath labs
17 MICU
6 central triage centers (randomization)
Grenoble
Valence
20 miles
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The AGIR2 investigators
RESCUe Network - Coordinator ElKhoury C
RESURCOR Network - Coordinator Belle L
MICU

• Amberieu Mann Y
• Annecy Savary D
• Belley Cognet / Florent O
• Bourg-en-Bresse Serre P
• Bourgoin Rodriguez JF
• CH Croix Rousse Guillaumee F.
• CH Ed. Herriot Capel O. / Dubien PY
• CH Lyon sud Fuster P. / David JS.
• Drôme Nord Genevey P. / Cheval B
• Grenoble Debaty G
• Montelimar Busseuil C. / Pajot F
• Privas Wahiche M
• Tarare Brilland R
• Valence Echahed K
• Vienne Matas O. / Bec JF
• Villefranche Guillemard T. / Boyer M
• Voiron Escallier C

Central Triage
SAMU 01 Maupoint R. SAMU 07 Wahiche M. SAMU
26 Echahed K. SAMU 38 Debaty G. SAMU 69 Dubien
PY. SAMU 74 Savary D.
CathLab
HCL L. Pradel Rioufol G. HCL Cx Rousse Besnard
C. St Joseph-St Luc Perret T. Clin.
Tonkin Champagnac D. Inf. Protestante Claudel
JP. Clin. Sauvegarde Hepp A. Valence Chapon
P CH Annecy Belle L. CHU Grenoble Vanzetto
G. Clin. Belledonne Guenot C. Clin.
Mutualiste Bourlard P.
AGIR2 Coordination
Coordination Bonnefoy E, Elkhoury C, Eydoux N,
A Peiretti, Statistical analysis Mercier C,
Bisery A, Ecochard R HCL Plattner V
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Study designClinicalTrials.gov Identifier
NCT00538317

• Sponsor University Hospital of Lyon (HCL),
  France
• Multicenter, randomized, open label comparison
• Statistical analysis Intention to treat
  Biostatistic Unit - HCL
• Data management clinical research center - Lyon
• Data analysis ECGs, biological and procedural
  reports but not coronary angiograms, centrally
  collected and analyzed
• Merck Co Inc and Iroko Laboratories supplied
  tirofiban free of charge to sponsor

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Enrollment Criteria

• Inclusion Criteria
• gt 18 years
• Ischemic pain gt 20 min and onset of symptoms lt 12
  hours
• ST elevation gt 1 mm in 2 contiguous limb leads
  or gt2 mm in 2 contiguous precordial leads
• Planned primary PCI
• Informed consent
• Major Exclusion Criteria
• High bleeding risk
• Fibrinolytics or GPIIbIIIa inhibitor lt 7 days
• Transfer to cath lab gt 90 min

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End Points

• Primary endpoint
• TIMI grade 2-3 flow at initial angiography
• Key secondary endpoints
• Complete (gt70) ST segment resolution one hour
  after procedure
• Troponin I and CK peaks

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Sample size calculation

• Initial sample size 300 patients with alpha risk
  5 and 80 power to detect a 16 difference in
  primary endpoint
• Patients wrongly randomized or who withdrew their
  informed consent before angiography were excluded
  from all analyses
• With regard to drop-outs, recruitment was
  increased to 337 patients, to have at least 155
  patients in each group

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Baseline characteristics
35
Angiographic procedures
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Time intervals and angiography
MICU
Cath lab
83
98
Cath lab Tirofiban
54
26
ANGIO
48
21
Pre-hospitalTirofiban
61
104
85
Times are expressed as median (min)
Plt0.05
37
TIMI grade 2-3 flow first angiography
P0.42
44.2
39.7
Pre-hospital tirofiban
Cath lab tirofiban
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ST segment resolution gt70
One hour after PCI
P0.64
55.4
52.6
On admission to Cath lab
P0.10
15.2
8.7
Cath lab tirofiban N148
Pre-hospital tirofiban N152
Cath lab tirofiban N127
Pre-hospital tirofiban N112
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ST segment resolution60 minutes
Residual ST segment 60 minutes
P0.07
P0.32
100
9.5
13.5
15.1
25
22.3
35.1
gt6 mm
32.2
20.4
4-6 mm
lt30
50
1-3 mm
39.9
30-70
30.3
0 mm
gt70
55.4
52.6
24.3
24.3
0
Cath lab tirofiban
Pre-hospital tirofiban
Cath lab tirofiban
Pre-hospital tirofiban
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Troponins and CK
42
In-hospital events
Cath lab tirofiban
Pre-Hospital tirofiban

p0.15
6
5.5
p0.15
5
3.7
4
p0.29
3.2
3
p0.26
1.9
2
1.3
1.2
0.6
0.6
1
0
Death
Severe Bleeding
Acute stent
Stroke
thrombosis
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Influence of time from onset of symptoms to
first medical contact

Cath lab tirofiban
Pre-Hospital tirofiban
lt 100 min gt median
65.7
70
56.6
60
51.2
50
48.6
50
39.7
39
37.3
40
30
P0.24
P0.25
P0.83
P0.87
20
10
0
TIMI 2-3
TIMI 2-3
ST 60 min gt70
ST 60 min gt70
P0.39
P0.26
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Influence of treatment period tirofiban to
angiography
p0.35

70
63.8
p0.11
60
54.3
49.3
46.0
45.5
50
lt10'
40
33.0
10'-45'
30
gt45'
(terciles)
20
10
0
TIMI 2-3 flow
ST 60 min gt70
45
Conclusion

• Early initiation of tirofiban in pre-hospital
  settings, prior to primary PCI and on top of a
  loading dose of clopidogrel, does not yield
  superior TIMI grade 2-3 flow in the culprit
  artery compared to initiation of tirofiban in the
  cardiac catheterization laboratory
• No beneficial effects on post-PCI angiography,
  ST-segment resolution or peak troponin levels
  were found

46
Clinical implication

• The AGIR2 study did not question benefits of
  upfront administration of GPIIbIIIa inhibitors in
  primary PCI
• Its results do not support the necessity to
  initiate tirofiban administration in pre-hospital
  settings