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

Jean G. Diodati; Jorge F. Saucedo; Tracy E. Cardillo; Joseph A. Jakubowski; Carsten Henneges; Mark B. Effron; Fred R. Lipkin; Joseph R. Walker; Suman Duvvuru; Scott S. Sundseth; Harold N. Fisher; Dominick J. Angiolillo

doi:10.1160/TH13-09-0747

Thrombosis and Haemostasis, Table of Contents

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

¹Division of Cardiology, Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada

,

Jorge F. Saucedo

²Division of Cardiology, NorthShore University Health System, Evanston, Illinois, USA

,

Tracy E. Cardillo

³Eli Lilly and Company, Indianapolis, Indiana, USA

,

Joseph A. Jakubowski

³Eli Lilly and Company, Indianapolis, Indiana, USA

,

Carsten Henneges

⁴Eli Lilly and Company, Bad Homburg, Germany

,

Mark B. Effron

³Eli Lilly and Company, Indianapolis, Indiana, USA

,

Fred R. Lipkin

⁵Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

,

Joseph R. Walker

⁵Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

,

Suman Duvvuru

³Eli Lilly and Company, Indianapolis, Indiana, USA

,

Scott S. Sundseth

⁶Cabernet Pharmaceuticals, Inc., Durham, North Carolina, USA

,

Harold N. Fisher

⁷Eli Lilly and Company, Toronto, Ontario, Canada

,

Dominick J. Angiolillo

⁸Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

› Author Affiliations

Abstract

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

Full Text

References

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