2. Conflits d’intérêts Je ne suis pas un garçon intéressé… Ma femme ne travaille plus chez Lilly !
3. Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events--a novel insight into plaque rupture by scanning electron microscopy. Abela GS et al. Scanning 2006;28:1-10.
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6. Influence of Time Dynamic thrombus formation Fibrin r=0.38, p=0.01 Platelets r=-0.34, p=0.02 Silvain J et al. JACC In press
7. Avis de recherche: AAP idéal Effet rapide Effet puissant Effet constant Sans effet secondaire délétère
8. 600 500 400 300 200 100 0 0 6 12 18 24 Clopidogrel and Prasugrel: active metabolite plasma concentrations following oral loading dose Clopidogrel300 mg LD Prasugrel60 mg LD Plasma Concentration (ng/mL) Time From Dose (hours) AM=Active metabolite; LD=Loading dose Payne C et al. ThrombHaemost 2005;3(Supplement 1):P0952
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10. Inhibition of Platelet Aggregation After Loading Dose in Patients With Elective PCI 100 *** *** *** 80 Prasugrel 60 mg *** 60 IPA % (20 µM ADP) Clopidogrel 600 mg 40 20 ***p<0.0001 Prasugrel vs. Clopidogrel 0 0.5 4 8 12 16 20 24 6 2 Hours IPA=inhibition of platelet aggregation; PCI=Percutaneous coronary intervention Wiviott SD et al. Circulation 2007;116(25):2923-2932
11. Background Variability Prasugrel60 mg LD Clopidogrel300 mg LD Crossover Study in Healthy Subjects Relationship between individual responses to prasugrel and clopidogrel, (administered in crossover fashion) as measured by IPA at 24 h postdose IPA % (20 mM ADP) Brandt JT et al. Am Heart J 2007;153(1):66.e9-16
21. TRITON: Efficacy for IIb/IIIa use. Prasugrel triple AP therapy more effective and as safe as Clopidogrel triple AP Therapy Percentage of subjects reaching the Primary Endpoint The trial was not randomized against GP IIb/IIIa inhibitors. As its use was left to the discretion of the physicians, patients receiving GPI were likely to be at higher risk for ischemic events.
22. En résumé… Effet rapide >> clopidogrel Effet puissant >> clopidogrel Effet constant >> clopidogrel Risque hémorragique > clopidogrel Population à risque identifiée GP IIbIIIa possibles dans le STEMI / souhaitables ?
26. 27 Bassand JP, et al. The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. European Heart Journal 2007, 28:1598-1660
29. Clopidogrel Prasugrel 2.5 2.4 p=0.65 2.0 2.1 1.5 1.0 Proportion of patients (%) 0.5 HR=1.11 (0.70–1.77) NNH=333 Age-adjusted HR=1.19 (0.75-1.89) 0 0 100 200 300 400 Time (Days) Montalescot et al. ESC 2008 TRITON STEMI: TIMI major non-CABG bleeding
30. Clopidogrel Prasugrel p=0.75 Life threatening bleeding (%) HR=1.11 (0.59–2.10) NNH=500 Age-adjusted HR=1.20 (0.63-2.26) Time (Days) TIMI life-threatening non-CABG bleeding Montalescot et al. ESC 2008
31. TRITON: Safety for IIb/IIIa use: No differences between Prasugrel and Clopidogrel at 3 days. The Co-Administration of a GP IIb/IIIa inhibitor with the loading dose increased the risk of instrumentation related TIMI major bleeding in both prasugrel- and clopidogrel-treated subjects, particularly in the STEMI population.
For ease of ease of use and convenience we developed a website Here is an example of the user interface. After entering in the appropriate range of values for each predictor, this online calculator will immediatiely provide an output of the CRUSADE Bleeding Score and the corresponding Risk of in-hospital major bleeding.