PRasugrel IN Comparison to Clopidogrel for Inhibition of
PRasugrel IN Comparison to Clopidogrel for Inhibition of PLatelet Activation and Aggr. Egation (PRINCIPLE) – TIMI 44 Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
Study Design Loading Phase N=201 Planned Elective PCI Baseline Laboratory Measures Clopidogrel 600 mg Clopidogrel naïve No planned GP IIb/IIIa use Prasugrel 60 mg 0. 5 h Post-Loading Dose Labs Coronary Angiography Post-Angiography Labs Maintenance Phase PCI No PCI 6 h* Labs, 18 -24 h Labs 6 h* Labs, 15 d Events N=100 Clopidogrel 150 mg x 14 d Prasugrel 10 mg x 14 d 15 d Clinical Events, Labs, † CROSSOVER 29 d Clinical Events, Labs† Prasugrel 10 mg x 14 d Clopidogrel 150 mg x 14 d 1º EPs: *Loading = 6 h IPA (20 µM ADP); †Maintenance = 15 d or 29 d IPA (20 µM ADP) Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
PRIMARY EP Acute Phase: IPA 20 u. M ADP IPA (%; 20 m. M ADP) P<0. 0001 for each Prasugrel 60 mg Hours Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
MPA (%; 20 m. M ADP) Maximal Platelet Aggregation (MPA) P<0. 0001 for each Prasugrel 60 mg Hours Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
VASP Phosphorylation Ratio P<0. 0001 for each Prasugrel 60 mg Hours Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
PRIMARY EP Chronic Phase: IPA 20 u. M ADP Difference Between Treatments: 14. 9 [95% CI 10. 6 – 19. 3], P<0. 0001 Prasugrel 10 mg IPA (%; 20 m. M ADP) Prasugrel 10 mg Days Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
Maximal Platelet Aggregation (MPA) MPA (%; 20 m. M ADP) Difference Between Treatments: 11. 3 [95% CI 8. 1 – 14. 5], P<0. 0001 Clopidogrel 150 mg Prasugrel 10 mg Days Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
VASP Phosphorylation Ratio Difference Between Treatments: 20. 1 [95% CI 14. 5 – 25. 7], P<0. 0001 Clopidogrel 150 mg Prasugrel 10 mg Days Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association Clopidogrel 150 mg
Thienopyridine Hyporesponsiveness: IPA 20 u. M ADP < 20% Percent of Subjects P =0. 0008 Clopidogrel Prasugrel P <0. 0001 P =0. 0005 P =0. 0002 P =0. 06 P =0. 18 Hours Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
Implications PRINCIPLE – TIMI 44 extends the pharmacologic superiority of the TRITON – TIMI 38 dose of prasugrel (60 mg/10 mg) to higher doses of clopidogrel (600 mg/150 mg) in PCI. TRITON – TIMI 381 tested hypothesis that an agent that with higher and more consistent IPA than standard approved clopidogrel (300 mg/ 75 mg) will improve clinical outcomes 1 Wiviott SD, Braunwald E, Mc. Cabe CH et al NEJM 2007 Wiviott SD et al, Circulation 2007 Copyright © 2007 American Heart Association
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