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The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel: A retrospective analysis of the FEATHER study
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2014 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 134, no 3, 552-557 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Patients treated with clopidogrel who have higher body size exhibit greater platelet reactivity than patients with lower body size. In a retrospective analysis of the FEATHER trial, we examined the relationship between platelet response to thienopyridines clopidogrel 75 mg (Clop-75), prasugrel 5 mg (Pras-5), and prasugrel 10 mg (Pras-10) using 3 body size indices: body weight (BW), body mass index (BMI), and body surface area (BSA). Relationships were assessed as continuous variables and as 4 incremental body size groups. Materials and Methods: Aspirin-treated patients with stable coronary artery disease (N = 72) and a BW range of 45-134 kg received Clop-75, Pras-5, and Pras-10 in a 3-period, blinded, cross-over study. Platelet assays included maximum platelet aggregation (MPA) to 20 mu M ADP by light transmission aggregometry, VerifyNow-P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation platelet reactivity index (PRI). Exposure to active metabolites (AMs) was also assessed. Results: Body size was a determinant of AM exposure and residual platelet reactivity regardless of type and dose of thienopyridine. BW and BSA demonstrated marginally stronger correlations with platelet reactivity; VASP-PRI demonstrated a stronger correlation with the body size than the other tests. Correlation coefficients ranged from a high of 0.64 (BW vs. PRI on Pras-5) to a low of 0.34 (BMI vs. MPA on Pras-10), but all were statistically significant (p < 0.01). Conclusions: Using a comprehensive selection of body size indices, AM exposures, platelet function tests, and thienopyridine doses, we demonstrated a consistent inverse relationship between body size and response to clopidogrel and prasugrel. (C) 2014 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
2014. Vol. 134, no 3, 552-557 p.
Keyword [en]
Body mass index, Clopidogrel, Pharmacodynamics, Pharmacokinetics, Prasugrel
National Category
Hematology Clinical Medicine
URN: urn:nbn:se:uu:diva-233579DOI: 10.1016/j.thromres.2014.05.019ISI: 000341310000006OAI: oai:DiVA.org:uu-233579DiVA: diva2:754959
Available from: 2014-10-13 Created: 2014-10-07 Last updated: 2014-10-13Bibliographically approved

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James, Stefan K.
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UCR-Uppsala Clinical Research Center
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