Faculty Collaboration Database

Transferring from clopidogrel loading dose to prasugrel loading dose in acute coronary syndrome patients. High on-treatment platelet reactivity analysis of the TRIPLET trial. Thromb Haemost 2014 Aug;112(2):311-22

Date

04/11/2014

Pubmed ID

24718367

DOI

10.1160/TH13-09-0747

Scopus ID

2-s2.0-84905184924 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

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.

Author List

Diodati JG, Saucedo JF, Cardillo TE, Jakubowski JA, Henneges C, Effron MB, Lipkin FR, Walker JR, Duvvuru S, Sundseth SS, Fisher HN, Angiolillo DJ

Author

Jorge Saucedo MD Chief, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Coronary Syndrome
Aged
Blood Platelets
Cytochrome P-450 CYP2C19
Double-Blind Method
Drug Administration Schedule
Drug Resistance
Drug Substitution
Female
Genotype
Humans
Male
Middle Aged
Percutaneous Coronary Intervention
Phenotype
Piperazines
Platelet Aggregation Inhibitors
Platelet Function Tests
Prasugrel Hydrochloride
Thiophenes
Ticlopidine
Time Factors
Treatment Outcome