N=483 Abciximab in the ER or cath lab

30-day MACE Any drug Int to treat(n=409) (n=483)

Control 12.0 11.2Abciximab 4.6 5.8P value 0.005 0.038

6-month MACE: no difference

Early vs. late : RAPPORT

Brenner & al. Am J Cardiol. 1999;84:728-30.

ReoPro in Acute myocardial infarction and Primary PTCA Organization Randomized Trial

Early vs. late : ON-TIME

43,0%

34,2%

0%

20%

40%

Early Late or No

• Early tirofiban administration was significantly associated with a greater frequency of TIMI 3 flow in the infarct-related artery before PCI.

• Similarly, incidence of myocardial perfusion grade 2-3 before PCI was significantly higher in the early treatment group (p=0.04).

• There were no differences in the two treatment arms in TIMI 3 flow after PCI, ST segment resolution, or 30-day clinical endpoints including death, reinfarction, stroke, and major bleeding.

TIMI 2-3 Flow in Culprit Artery Pre-PCIp = 0.04

Van’tHof & al. Eur Heart J 2004;25:807

Early vs. late : INTAMI

34,0%

10,2%

0%

5%

10%

15%

20%

25%

30%

35%

Early Late or No

• Early eptifibatide administration was significantly associated with a greater frequency of TIMI 3 flow in the infarct-related artery before PCI.

• Similarly, incidence of TIMI myocardial perfusion grade 3 before PCI was significantly higher in the early treatment group (p=0.01).

• There were no differences in the two treatment arms in TIMI 3 flow after PCI, ST segment resolution, or 30-day clinical endpoints including death, reinfarction, stroke, and major bleeding.

TIMI 3 Flow in Culprit Artery Pre-PCIp = 0.01

Zeymzer & al. Eur Heart J 2005;26:1971

Early vs. late : Admiral

Montalescot & al. N Engl J Med 2001;344:1895

Early vs. late : Admiral

Montalescot & al. N Engl J Med 2001;344:1895

Corrélation délai AntiGP-PCI et Mortalité à 30jEarlier is better !

Admiral, Erami, On time, Relax, Reomobile, Tiger, Titan, Zorma & al - N=875 pts

0123456789

10

0 30 60 90Anti Gp to PCI time (min)

30

days

mort

alit

y (

%)

Corrélation délai AntiGP-PCI et Mortalité à 30jEarlier is better !

Admiral, Erami, On time, Relax, Reomobile, Tiger, Titan, Zorma & al - N=875 pts

y = 0,0007x2 - 0,0935x + 5,1097

R2 = 0.94

0123456789

10

0 30 60 90Anti Gp to PCI time (min)

30 d

ays

mort

alit

y (%

)

y = 0,0007x2 - 0,0935x + 5,1097

R2 = 0.94

0123456789

10

0 30 60 90Anti Gp to PCI time (min)

30 d

ays

mort

alit

y (%

)

4.9%

3.1%1.8%

Les questions

Chez les patients bénéficiant d’une ACT première pour IDM ST +, une administration précoce d’antiGP2b3 apporte-t-elle un bénéfice par rapport à une utilisation péri-PCI en terme de : paramètres angiographiques : OUI critères pronostiques intermédiaires : OUI MACEs (décès, ré-IDM) : OUI…probablement

RECOMMANDATIONS

ESC 2003

I : Current data support the use of abciximab in combination with low dose heparine in primary coronary angioplasty

ACC/AHA 2004

IIA : It is reasonable to start treatment with abciximab as early as possible before primary PCI (with or without stenting) in patients with STEMI

IIB : Treatment with tirofiban or eptifibatide may be considered before primary PCI (with or without stenting) in patients with STEMI

Les questions

Faut-il initier un traitement par anti GP2b3a en préhospitalier :

Dans l’infarctus ST + en association avec la thrombolyse : NON

Dans l’infarctus ST + avant angioplastie première : OUI

Dans les SCA non ST+ ?

Les questions

Faut-il initier un traitement par anti GP2b3a en préhospitalier :

Dans l’infarctus ST + en association avec la thrombolyse : NON

Dans l’infarctus ST + avant angioplastie première : OUI

Dans les SCA non ST+ ?

Bénéfice des AntiGP dans les SCA non ST+

Boersma & al.Lancet 2002; 359: 189–98

Bénéfice des AntiGP dans les SCA non ST+

Boersma & al.Lancet 2002; 359: 189–98

Stratification / Troponine

Morrow et al. JAMA 2001;286:2405–12.

Stratification / Score de risque

Lanuzzi et al. Am Heart J 2003;146:764–74.

Bénéfice des AntiGP dans les SCA non ST+

Boersma & al.Lancet 2002; 359: 189–98

RECOMMANDATIONS

ESC 2003

I : High risk patients require aggressive antiplatelet treatment with blockade of the 3 principal pathways (ASA, clopidogrel, GpIIb/IIIa) with rapid invasive strategy prepared by upstream treatment.

ACC/AHA 2002

I : A platelet GP IIb/IIIa antagonist, should be administered, in addition to aspirin and heparin, to patients in whom catheterization and PCI are planned. The GP IIb/IIIa antagonist may also be administered just prior to PCI.

IIa : A platelet GP IIb/IIIa antagonist should be administered to patients already receiving heparin, aspirin, and clopidogrel in whom catheterization and PCI are planned. The GP IIb/IIIa antagonist may also be administered just prior to PCI

Early vs. Late : EVEREST

Bolognese & al. J Am Coll Cardiol 2006;47:522– 8

Early vs. Late : EVEREST

Bolognese & al. J Am Coll Cardiol 2006;47:522– 8

Early vs. Late : EVEREST

Bolognese & al. J Am Coll Cardiol 2006;47:522– 8

Early vs. Late : EVEREST

Bolognese & al. J Am Coll Cardiol 2006;47:522– 8

This pilot study shows that in high-risk NSTE-ACS, an early

invasive strategy with upstream tirofiban is associated with

improved tissue-level perfusion and attenuated myocardial

damage, compared with an early invasive strategy with

downstream HDB tirofiban or abciximab.

Early vs. Late : Acuity Timing Trial

Population : 9207 pts with moderate- and high-risk ACS undergoing an invasive strategy Method : random assignation to routine upstream (n=4605) or downstream selective (n=4602) Gp

IIb/IIIa inhibitor administration End point : death, MI, or unplanned revascularization for ischemia

Treatments :

Stone et al. JAMA. 2007 ;297:591-602

Upstream Downstream P

Any GP2b3a (%) 98 56 < 0.001 Eptifibatide (%) 65 57Tirofiban (%) 34 4 < 0.01Abciximab (%) 1 33GP-PCI time (h) 4.1 0.6 < 0.001Duration (h) 18 13 < 0.01PrePCI ASA+CLO (%) 64 63 NS

Early vs. Late : Acuity Timing Trial

30-D results

Stone et al. JAMA. 2007 ;297:591-602

% Upstream Downstream P

Death+MI+Rev 7.1 7.9 NSDeath from any cause 1.3 1.5 NSMI 4.9 5.0 NSUnplanned revasc. 2.1 2.8 NS

Major bleeding 6.1 4.9 0.001HIC 0.04 0.09 NSRetroperitoneal 0.6 0.5 NSAccess site 2.7 2.4 NSB. requiring surgery 0.5 0.7 NSBlood transfuson 3.0 2.3 0.05

Minor bleeding 7.1 5.4 0.001

Men 0.08 65 years 0.08 ST depression 0.02 Planned PCI 0.15

Men 0.08 65 years 0.08 ST depression 0.02 Planned PCI 0.15

Early vs. Late : EARLY-ACS

To demonstrate the superiority of early eptifibatide compared to placebo (with provisional use of eptifibatide in the cath lab) in reducing the composite of death, MI, recurrent ischemia, and thrombotic bail-out within 96 hours in patients with high-risk NSTE ACS managed with an early invasive strategy (N=10500).

Les questions

Faut-il initier un traitement par anti GP2b3a en préhospitalier :

Dans l’infarctus ST + en association avec la thrombolyse : NON

Dans l’infarctus ST + avant angioplastie première : OUI

Dans les SCA non ST+ : ?

Conclusion

Pour l’angioplastie première, nous proposons l’administration d’anti-GP IIb/IIIa (ABCIXIMAB en priorité) en pré hospitalier,

associé à 300 mg de CLOPIDOGREL, 250 à 500 mg d’ASPIRINE quel que soit l’âge et l’HNF. Si un anti-GP IIb/IIIa ne peut être utilisé, nous proposons l’administration de 600 mg de CLOPIDOGREL le plus rapidement possible et

quel que soit l’âge.