European Heart Journal Advance Access published online on May 12, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp159
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Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial
1 Center for Platelet Research Studies, Division of Hematology/Oncology, Department of Medicine, Children's Hospital Boston, 300 Longwood Avenue, Karp 08213, Boston, MA 02115, USA
2 Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3 Department of Pediatrics, Center for Platelet Function Studies, University of Massachusetts Medical School, Room S5-846, 55 Lake Avenue North, Worcester, MA 01655, USA
4 Department of Medicine, Center for Platelet Function Studies, University of Massachusetts Medical School, Worcester, MA, USA
5 Department of Pathology, Center for Platelet Function Studies, University of Massachusetts Medical School, Worcester, MA, USA
6 TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, USA
7 LeBauer Cardio Research, Greensboro, NC, USA
8 University of Florida College of Medicine, Jacksonville, FL, USA
9 Cardiovascular Specialists, Louisville, KY, USA
10 Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN, USA
11 Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA, USA
Received 18 November 2008; revised 1 March 2009; accepted 20 March 2009 * Corresponding author. Tel: +1 617 919 2697, Fax: +1 617 730 0934, Email: michelson{at}platelets.org
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 (
1 h after loading dose) (P < 0.001) and at 30 days (P < 0.001). Maximal platelet aggregation to 20 µM 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 µM 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 < 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.
Key Words: Platelets • Prasugrel • Clopidogrel • Clinical trials • Platelet function
These authors contributed equally to this manuscript.
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