Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial.
OBJECTIVE
To examine the extent of platelet inhibition by prasugrel vs. clopidogrel in a TRITON-TIMI 38 substudy.


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 < 0.001) and at 30 days (P < 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 < 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.
Department of Medicine, Children's Hospital Boston, Center for Platelet Research Studies, Division of Hematology/Oncology, Boston, MA 02115, USA. michelson@platelets.org
Alan D
AD
Michelson
Andrew L
AL
Frelinger
Eugene
E
Braunwald
William E
WE
Downey
Dominick J
DJ
Angiolillo
Nicholas P
NP
Xenopoulos
Joseph A
JA
Jakubowski
Youfu
Y
Li
Sabina A
SA
Murphy
Jie
J
Qin
Carolyn H
CH
McCabe
Elliott M
EM
Antman
Stephen D
SD
Wiviott
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000244:Adenosine Diphosphate / Q000378:metabolism; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine