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, Alan D.; Frelinger, Andrew L. III; Braunwald, Eugene; Downey, William E.; Angiolillo, Dominick J.; Xenopoulos, Nicholas P.; Jakubowski, Joseph A.; Li, YouFu; Murphy, Sabina A.; Qin, Jie; McCabe, Carolyn H.; Antman, Elliott M.; and Wiviott, Stephen D., "Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial" (2009). Hematology/Oncology. 117.