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Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial

Prasugrel, a novel P2Y(12) receptor antagonist, has been shown to be more effective than clopidogrel for preventing cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. We investigated the dose–response antiplatelet effects of prasugrel compa...

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Autores principales: Yamaguchi, Takenori, Shirai, Toshiaki, Yoshiba, Satoshi, Abe, Kenji, Ikeda, Yasuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954144/
https://www.ncbi.nlm.nih.gov/pubmed/31643039
http://dx.doi.org/10.1007/s11239-019-01926-6
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author Yamaguchi, Takenori
Shirai, Toshiaki
Yoshiba, Satoshi
Abe, Kenji
Ikeda, Yasuo
author_facet Yamaguchi, Takenori
Shirai, Toshiaki
Yoshiba, Satoshi
Abe, Kenji
Ikeda, Yasuo
author_sort Yamaguchi, Takenori
collection PubMed
description Prasugrel, a novel P2Y(12) receptor antagonist, has been shown to be more effective than clopidogrel for preventing cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. We investigated the dose–response antiplatelet effects of prasugrel compared with clopidogrel in Japanese patients with non-cardioembolic stroke. The influence of cytochrome P450 (CYP) polymorphisms on the antiplatelet effects of both drugs was also compared. In this multicenter randomized active-control comparative study, patients were randomized to receive prasugrel 2.5 mg, 5 mg, or 7.5 mg (double blind) or clopidogrel 75 mg (open label) once daily for 14 days. The primary endpoint was inhibition of platelet aggregation (IPA) in response to adenosine diphosphate 20 μM within 8 h of study drug administration on day 14. Of the 66 patients randomized, data from 63 (prasugrel 2.5 mg, 5 mg, and 7.5 mg groups, n = 14, 16, and 18, respectively; clopidogrel group, n = 15) were used in the pharmacodynamic assessment. IPA (arithmetic mean ± SD) after prasugrel administration increased dose-dependently (33 ± 9%, 44 ± 11%, and 53 ± 14%, at 2.5 mg, 5 mg, and 7.5 mg, respectively) and was higher in these groups than after clopidogrel (23 ± 16%). In a subgroup of CYP2C19 intermediate metabolizers, IPA was higher in the prasugrel 5 mg and 7.5 mg groups than in the clopidogrel group. No death or serious adverse events were reported. Prasugrel was well tolerated at doses up to 7.5 mg/day and had antiplatelet effects higher than those of clopidogrel 75 mg/day. CYP2C19 polymorphisms may have reduced clopidogrel-induced IPA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-019-01926-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-69541442020-01-23 Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial Yamaguchi, Takenori Shirai, Toshiaki Yoshiba, Satoshi Abe, Kenji Ikeda, Yasuo J Thromb Thrombolysis Article Prasugrel, a novel P2Y(12) receptor antagonist, has been shown to be more effective than clopidogrel for preventing cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. We investigated the dose–response antiplatelet effects of prasugrel compared with clopidogrel in Japanese patients with non-cardioembolic stroke. The influence of cytochrome P450 (CYP) polymorphisms on the antiplatelet effects of both drugs was also compared. In this multicenter randomized active-control comparative study, patients were randomized to receive prasugrel 2.5 mg, 5 mg, or 7.5 mg (double blind) or clopidogrel 75 mg (open label) once daily for 14 days. The primary endpoint was inhibition of platelet aggregation (IPA) in response to adenosine diphosphate 20 μM within 8 h of study drug administration on day 14. Of the 66 patients randomized, data from 63 (prasugrel 2.5 mg, 5 mg, and 7.5 mg groups, n = 14, 16, and 18, respectively; clopidogrel group, n = 15) were used in the pharmacodynamic assessment. IPA (arithmetic mean ± SD) after prasugrel administration increased dose-dependently (33 ± 9%, 44 ± 11%, and 53 ± 14%, at 2.5 mg, 5 mg, and 7.5 mg, respectively) and was higher in these groups than after clopidogrel (23 ± 16%). In a subgroup of CYP2C19 intermediate metabolizers, IPA was higher in the prasugrel 5 mg and 7.5 mg groups than in the clopidogrel group. No death or serious adverse events were reported. Prasugrel was well tolerated at doses up to 7.5 mg/day and had antiplatelet effects higher than those of clopidogrel 75 mg/day. CYP2C19 polymorphisms may have reduced clopidogrel-induced IPA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-019-01926-6) contains supplementary material, which is available to authorized users. Springer US 2019-10-23 2020 /pmc/articles/PMC6954144/ /pubmed/31643039 http://dx.doi.org/10.1007/s11239-019-01926-6 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Yamaguchi, Takenori
Shirai, Toshiaki
Yoshiba, Satoshi
Abe, Kenji
Ikeda, Yasuo
Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
title Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
title_full Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
title_fullStr Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
title_full_unstemmed Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
title_short Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
title_sort pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954144/
https://www.ncbi.nlm.nih.gov/pubmed/31643039
http://dx.doi.org/10.1007/s11239-019-01926-6
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