Transferring from clopidogrel loading dose to prasugrel loading dose in acute coronary syndrome patients. High on-treatment platelet reactivity analysis of the TRIPLET trial.
High on-treatment platelet reactivity (HPR) has been identified as an independent risk factor for ischaemic events. The randomised, double-blind, TRIPLET trial included a pre-defined comparison of HPR in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) following a placebo/600-mg clopidogrel loading dose (LD) immediately before a subsequent prasugrel 60-mg or 30-mg LD. Platelet reactivity was assessed using the VerifyNow® P2Y12 assay (P2Y12 Reaction Units, PRU) within 24 hours (h) following the placebo/clopidogrel LD (immediately prior to prasugrel LD), and at 2, 6, 24, 72 h following prasugrel LDs. The impact of CYP2C19 predicted metaboliser phenotype (extensive metabolisers [EM] and reduced metabolisers [RM]) on HPR status was also assessed. HPR (PRU ≥240) following the clopidogrel LD (prior to the prasugrel LD) was 58.5% in the combined clopidogrel LD groups. No significant difference was noted when stratified by time between the clopidogrel and prasugrel LDs (≤6 hs vs>6 h). At 6 h following the 2nd loading dose in the combined prasugrel LD groups, HPR was 7.1%, with 0% HPR by 72 h. There was no significant effect of CYP2C19 genotype on pharmacodynamic (PD) response following either prasugrel LD treatments at any time point, regardless of whether it was preceded by a clopidogrel 600-mg LD. In conclusion, in this study, patients with ACS intended for PCI showed a high prevalence of HPR after clopidogrel 600-mg LD regardless of metaboliser status. When prasugrel LD was added, HPR decreased substantially by 6 h, and was not seen by 72 h.
Jean G. Diodati, Address: Hôpital du Sacré-Coeur de Montréal,, 5400 Gouin Boulevard West, Montreal, Quebec, H4J 1C5 Canada, Tel.: +1 514 338 2222 extension 2200, Fax: +1 514 338 3556, E-mail: jean.gino.diodati@umontreal.ca.
J G
JG
Diodati
J F
JF
Saucedo
T E
TE
Cardillo
J A
JA
Jakubowski
C
C
Henneges
M B
MB
Effron
F R
FR
Lipkin
J R
JR
Walker
S
S
Duvvuru
S S
SS
Sundseth
H N
HN
Fisher
D J
DJ
Angiolillo
D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D057915:Drug Substitution; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010641:Phenotype; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
Clopidogrel; acute coronary syndrome; high on-treatment platelet reactivity; platelet function; prasugrel