Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial
Department of Pediatrics
Acute Coronary Syndrome; Adenosine Diphosphate; Angioplasty, Balloon, Coronary; Cell Adhesion Molecules; Female; Humans; Male; Microfilament Proteins; Middle Aged; Myocardial Infarction; Phosphoproteins; Phosphorylation; Piperazines; Platelet Aggregation Inhibitors; Thiophenes; Ticlopidine
Hematology | Oncology | Pediatrics
AIMS: To examine the extent of platelet inhibition by prasugrel vs. clopidogrel in a TRITON-TIMI 38 substudy.
METHODS AND RESULTS: TRITON-TIMI 38 randomized acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) to prasugrel or standard dose clopidogrel. Selected sites prospectively enrolled TRITON-TIMI 38 patients to evaluate adenosine diphosphate (ADP)-attenuated phosphorylation of platelet vasodilator-stimulated phosphoprotein (VASP) (n = 125 patients) and, in a subset (n = 31 patients), ADP-stimulated platelet aggregation. VASP platelet reactivity index (PRI) was lower in prasugrel-treated patients than in clopidogrel-treated patients at 1-2 h post-PCI (>or=1 h after loading dose) (P andlt; 0.001) and at 30 days (P andlt; 0.001). Maximal platelet aggregation to 20 microM ADP was lower in prasugrel-treated patients than in clopidogrel-treated patients at 1-2 h (P = 0.004) and 30 days (P = 0.03). Results were similar with 5 microM ADP. Thienopyridine hyporesponsiveness, prespecified as VASP PRI >50%, was more frequent in clopidogrel-treated patients than in prasugrel-treated patients at 1-2 h (P andlt; 0.001) and 30 days (P = 0.03).
CONCLUSIONS: The TRITON-TIMI 38 platelet substudy shows that prasugrel results in greater inhibition of ADP-mediated platelet function in ACS patients than clopidogrel, supporting the hypothesis that greater platelet inhibition leads to a lower incidence of ischaemic events and more bleeding both early and late following PCI.
DOI of Published Version
Eur Heart J. 2009 Jul;30(14):1753-63. Epub 2009 May 12. doi 10.1093/eurheartj/ehp159
European heart journal
Michelson AD, Frelinger AL, Braunwald E, Downey WE, Angiolillo DJ, Xenopoulos NP, Jakubowski JA, Li Y, Murphy SA, Qin J, McCabe CH, Antman EM, Wiviott SD. (2009). Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Hematology/Oncology. https://doi.org/10.1093/eurheartj/ehp159. Retrieved from https://escholarship.umassmed.edu/peds_hematology/117