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Thromb Haemost 2014; 112(02): 311-322
DOI: 10.1160/TH13-09-0747
Platelets and Blood Cells
Schattauer GmbH

Transferring from clopidogrel loading dose to prasugrel loading dose in acute coronary syndrome patients

High on-treatment platelet reactivity analysis of the TRIPLET trial
Jean G. Diodati
1   Division of Cardiology, Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada
,
Jorge F. Saucedo
2   Division of Cardiology, NorthShore University Health System, Evanston, Illinois, USA
,
Tracy E. Cardillo
3   Eli Lilly and Company, Indianapolis, Indiana, USA
,
Joseph A. Jakubowski
3   Eli Lilly and Company, Indianapolis, Indiana, USA
,
Carsten Henneges
4   Eli Lilly and Company, Bad Homburg, Germany
,
Mark B. Effron
3   Eli Lilly and Company, Indianapolis, Indiana, USA
,
Fred R. Lipkin
5   Daiichi Sankyo, Inc., Parsippany, New Jersey, USA
,
Joseph R. Walker
5   Daiichi Sankyo, Inc., Parsippany, New Jersey, USA
,
Suman Duvvuru
3   Eli Lilly and Company, Indianapolis, Indiana, USA
,
Scott S. Sundseth
6   Cabernet Pharmaceuticals, Inc., Durham, North Carolina, USA
,
Harold N. Fisher
7   Eli Lilly and Company, Toronto, Ontario, Canada
,
Dominick J. Angiolillo
8   Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
› Author Affiliations Financial support: This analysis was sponsored by Daiichi Sankyo, Inc. and Eli Lilly and Company.
Further Information

Publication History

Received: 09 September 2013

Accepted after major revision: 27 February 2014

Publication Date:
04 December 2017 (online)

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Summary

High on-treatment platelet reactivity (HPR) has been identified as an independent risk factor for ischaemic events. The randomised, doubleblind, 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 metaboliser [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.

Keywords

Clopidogrel - prasugrel - acute coronary syndrome - platelet function - high on-treatment platelet reactivity
 

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