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Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo.

Author:
  • David Erlinge
  • Christoph Varenhorst
  • Oscar Braun
  • Stefan James
  • Kenneth J Winters
  • Joseph A Jakubowski
  • John T Brandt
  • Atsuhiro Sugidachi
  • Agneta Siegbahn
  • Lars Wallentin
Publishing year: 2008
Language: English
Pages: 1968-1977
Publication/Series: Journal of the American College of Cardiology
Volume: 52
Issue: 24
Document type: Journal article
Publisher: Elsevier

Abstract english

OBJECTIVES: We evaluated the prevalence and mechanism of poor responsiveness to clopidogrel and prasugrel in coronary artery disease patients with and without diabetes. BACKGROUND: Low platelet inhibition by clopidogrel is associated with ischemic clinical events. A higher 600-mg loading dose (LD) has been advocated to increase responsiveness to clopidogrel. METHODS: In this study, 110 aspirin-treated patients were randomized to double-blind treatment with clopidogrel 600 mg LD/75 mg maintenance dose (MD) for 28 days or prasugrel 60 mg LD/10 mg MD for 28 days. Pharmacodynamic (PD) response was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The PD poor responsiveness was defined with 4 definitions previously associated with worse clinical outcomes. Active metabolites (AM) of clopidogrel and prasugrel were measured. Clopidogrel AM was added ex vivo. RESULTS: The proportion of patients with poor responsiveness was greater in the clopidogrel group for all definitions at all time points from 1 h to 29 days. Poor responders had significantly lower plasma AM levels compared with responders. Patients with diabetes were over-represented in the poor-responder groups and had significantly lower levels of AM. Platelets of both poor responders and diabetic patients responded fully to AM added ex vivo. CONCLUSIONS: Prasugrel treatment results in significantly fewer PD poor responders compared with clopidogrel after a 600-mg clopidogrel LD and during MD. The mechanism of incomplete platelet inhibition in clopidogrel poor-responder groups and in diabetic patients is lower plasma levels of its AM and not differences in platelet P2Y(12) receptor function.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • ISSN: 0735-1097
E-mail: oscar.braun [at] med.lu.se

Physician

Cardiology

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Research project participant

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