AGIR 2 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
Embed
AGIR 2 Presenter Disclosure Information Eric Bonnefoy The following relationships exist related to this presentation: Research grantsMerck & Co, Iroko.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
AGIR2
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
AGIR2
Comparison of Pre-hospital or Cath lab Administration of High Dose Tirofiban
in Patients Undergoing Primary Angioplasty
The AGIR2 Study
Eric Bonnefoy
on behalf of AGIR2 investigators and RESCUe and RESURCOR networks
Hospices Civils de Lyon, France
RESURCORRESURCOR
AGIR2Background
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
AGIR2
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
AGIR2
MICUPatient
call
STEMI undergoing primary PCI
600 mg clopidogrel250 mg aspirinUFH 60 U/kg + inf
Tirofiban25/0.15
Tirofiban25/0.15
AngiographyAngiography
Pre-hospital
MICUtransportation
Cath lab
Randomize Open Label
Medical Dispatcher
AGIR2
RESURCORRESURCOR
11 cath labs
17 MICU
20 miles
6 central triage centers (randomization)
Lyon
Annecy
Grenoble
Mont Blanc
Valence
AGIR2
The AGIR2 investigators
Amberieu Mann YAnnecy Savary DBelley Cognet / Florent OBourg-en-Bresse Serre PBourgoin Rodriguez JFCH Croix Rousse Guillaumee F.CH Ed. Herriot Capel O. / Dubien PYCH Lyon sud Fuster P. / David JS.Drôme Nord Genevey P. / Cheval BGrenoble Debaty GMontelimar Busseuil C. / Pajot FPrivas Wahiche MTarare Brilland RValence Echahed KVienne Matas O. / Bec JFVillefranche Guillemard T. / Boyer MVoiron Escallier C
RESCUe Network - Coordinator : ElKhoury C RESURCOR Network - Coordinator : Belle L
Coordination : Bonnefoy E, Elkhoury C, Eydoux N, A Peiretti, Statistical analysis : Mercier C, Bisery A, Ecochard RHCL : Plattner V
AGIR2
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
AGIR2
Enrollment CriteriaInclusion Criteria
• > 18 years • Ischemic pain > 20 min and onset of symptoms < 12 hours• ST elevation > 1 mm in 2 contiguous limb leads
or >2 mm in 2 contiguous precordial leads• Planned primary PCI• Informed consent
Major Exclusion Criteria• High bleeding risk• Fibrinolytics or GPIIbIIIa inhibitor < 7 days• Transfer to cath lab > 90 min
AGIR2
End Points
Primary endpoint
TIMI grade 2-3 flow at initial angiography
Key secondary endpoints
• Complete (>70%) ST segment resolution one hour after procedure
• Troponin I and CK peaks
AGIR2
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
AGIR2
Baseline characteristicsCath lab tirofiban
N=156
Pre-hospital tirofiban
N=164 p
Age 62.5+12.5 64.1+13.6 0.25
Male 79.5% 75% 0.34
Diabetes 10.9% 11.0% 0.98
Anterior AMI 43.6% 51.2% 0.17
Killip class >2 8.3% 11.6% 0.33
Onset < 6hrs 90.4% 86.0% 0.61
Previous PCI 14.7% 7.9% 0.05
AGIR2
Angiographic procedures
Cath lab tirofiban
N=156
Pre-hospital tirofiban
N=163 p
Thrombus aspiration 32.7% 40.8% 0.13
Bare metal stent 72.4% 69.1% 0.52
Drug eluting stent 8.3% 8.5% 0.92
AGIR2Time intervals and angiography
Pre-hospitalTirofiban
98
10461*
21
26 *
Times are expressed as median (min)
Cath lab Tirofiban 54
48
83
85
MICU Cath lab
* P<0.05
ANGIO
AGIR2TIMI grade 2-3 flow
first angiography
Pre-hospital tirofiban
39.7%44.2%
P=0.42
Cath lab tirofiban
AGIR2
Initial TIMI grade flow
Cath lab tirofibanN=156
Pre-hospital tirofibanN=163 p
TIMI 3 30.8% 32.5%0.52TIMI 2 9.0% 11.7%
TIMI 0-1 60.3% 55.8%Final TIMI grade flow
TIMI 3 91.7% 93.3%0.98TIMI 2 6.4% 3.7%
TIMI 0-1 1.9% 3.0%
AGIR2ST segment resolution >70%
Cath lab tirofiban
N=148
Pre-hospital tirofiban
N=152
55.4% 52.6%
P=0.64
Cath lab tirofiban
N=127
Pre-hospital tirofiban
N=112
8.7% 15.2%P=0.10
On admission to Cath lab
One hour after PCI
AGIR2
0%
50%
100%
Cath lab tirofiban
Pre-hospitaltirofiban
<30%
30-70%
>70%55.4 52.6
35.1 32.2
9.5 15.1
P=0.32
24.3 24.3
39.9 30.3
22.320.4
13.525
P=0.07
>6 mm
4-6 mm
1-3 mm
0 mm
Cath lab tirofiban
Pre-hospitaltirofiban
ST segment resolution60 minutes
Residual ST segment 60 minutes
AGIR2
Troponins and CK
Cath lab tirofibanN=152
Pre-hospital tirofibanN=163
p
CK max - UI 1860+1568 2220+2202 0.10CK 24 hrs - UI 1047+907 1057+928 0.90
Troponin I max ng/ml 41.8+68.7 57.9+132.0 0.18Troponin I 24 hrs ng/ml 23.6+34.3 30.6+87.3 0.26
AGIR2
3.2
1.31.9
0.6
5.5
3.7
0.61.2
0
1
2
3
4
5
6
Death Severe Bleeding Acute stentthrombosis
Stroke
Cath lab tirofiban Pre-Hospital tirofiban% p=0.15
p=0.15
p=0.29p=0.26
In-hospital events
AGIR2
39.7
65.7
39
48.651.256.6
37.3
50
0
10
20
30
40
50
60
70
TIMI 2-3 ST 60 min >70% TIMI 2-3
Cath lab tirofiban Pre-Hospital tirofiban
Influence of time from onset of symptoms to first medical contact
< 100 min >
median
P=0.24 P=0.25 P=0.83 P=0.87
%
P=0.26 P=0.39
ST 60 min >70%
AGIR2Influence of treatment period tirofiban to angiography
p=0.35
p=0.11
33.0
63.8
46.049.3
45.5
54.3
0
10
20
30
40
50
60
70
TIMI 2-3 flow ST 60 min >70%
<10'10'-45'>45'
%
(terciles)
AGIR2
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
AGIR2Clinical 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