Cargando…

Prasugrel in critically ill patients

While prasugrel is indicated for the treatment of myocardial infarction, its effects in the most severely affected patients requiring intensive care is unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics of prasugrel in critically ill patients. Twenty-three patients adm...

Descripción completa

Detalles Bibliográficos
Autores principales: Schoergenhofer, Christian, Hobl, Eva-Luise, Staudinger, Thomas, Speidl, Walter S., Heinz, Gottfried, Siller-Matula, Jolanta, Zauner, Christian, Reiter, Birgit, Kubica, Jacek, Jilma, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Schattauer GmbH 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292180/
https://www.ncbi.nlm.nih.gov/pubmed/28692105
http://dx.doi.org/10.1160/TH17-03-0154
_version_ 1783380367865020416
author Schoergenhofer, Christian
Hobl, Eva-Luise
Staudinger, Thomas
Speidl, Walter S.
Heinz, Gottfried
Siller-Matula, Jolanta
Zauner, Christian
Reiter, Birgit
Kubica, Jacek
Jilma, Bernd
author_facet Schoergenhofer, Christian
Hobl, Eva-Luise
Staudinger, Thomas
Speidl, Walter S.
Heinz, Gottfried
Siller-Matula, Jolanta
Zauner, Christian
Reiter, Birgit
Kubica, Jacek
Jilma, Bernd
author_sort Schoergenhofer, Christian
collection PubMed
description While prasugrel is indicated for the treatment of myocardial infarction, its effects in the most severely affected patients requiring intensive care is unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics of prasugrel in critically ill patients. Twenty-three patients admitted to medical intensive care units, who were treated with 10 mg prasugrel once daily, were included in this prospective trial. Critically ill patients responded poorly to daily prasugrel treatment: adenosine diphosphate (ADP)-induced aggregation in whole blood classified 65 % (95 % confidence intervals (CI) 43–84 %) of patients as having high on treatment platelet reactivity, platelet function under high shear rates even 74 % (95 %CI 52–90 %). There was only limited additional inhibition provided 2 hours after the next dose of prasugrel. In contrast, insufficient inhibition of the target was only seen in 26 % (95 %CI 10–48 %) of patients as measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. Low effective plasma levels of prasugrel active metabolite were measured at trough [0.5 (quartiles 0.5–1.1) ng/ml at baseline], and 2 hours after intake [5.7 (3.8–9.8) ng/ml], but showed coefficients of variation of ~70 %. In sum, inhibition of platelet aggregation by prasugrel is not uniform but highly variable in critically ill patients, similar to clopidogrel in a general population. The pharmacokinetic measurements indicate that poor absorption/metabolism of prasugrel may partly contribute while inflammation induced heightened intrinsic platelet reactivity may also play a role. Supplementary Material to this article is available online at www.thrombosis-online.com . Note: This work was performed at the Medical University of Vienna, Austria.
format Online
Article
Text
id pubmed-6292180
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Schattauer GmbH
record_format MEDLINE/PubMed
spelling pubmed-62921802018-12-13 Prasugrel in critically ill patients Schoergenhofer, Christian Hobl, Eva-Luise Staudinger, Thomas Speidl, Walter S. Heinz, Gottfried Siller-Matula, Jolanta Zauner, Christian Reiter, Birgit Kubica, Jacek Jilma, Bernd Thromb Haemost While prasugrel is indicated for the treatment of myocardial infarction, its effects in the most severely affected patients requiring intensive care is unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics of prasugrel in critically ill patients. Twenty-three patients admitted to medical intensive care units, who were treated with 10 mg prasugrel once daily, were included in this prospective trial. Critically ill patients responded poorly to daily prasugrel treatment: adenosine diphosphate (ADP)-induced aggregation in whole blood classified 65 % (95 % confidence intervals (CI) 43–84 %) of patients as having high on treatment platelet reactivity, platelet function under high shear rates even 74 % (95 %CI 52–90 %). There was only limited additional inhibition provided 2 hours after the next dose of prasugrel. In contrast, insufficient inhibition of the target was only seen in 26 % (95 %CI 10–48 %) of patients as measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. Low effective plasma levels of prasugrel active metabolite were measured at trough [0.5 (quartiles 0.5–1.1) ng/ml at baseline], and 2 hours after intake [5.7 (3.8–9.8) ng/ml], but showed coefficients of variation of ~70 %. In sum, inhibition of platelet aggregation by prasugrel is not uniform but highly variable in critically ill patients, similar to clopidogrel in a general population. The pharmacokinetic measurements indicate that poor absorption/metabolism of prasugrel may partly contribute while inflammation induced heightened intrinsic platelet reactivity may also play a role. Supplementary Material to this article is available online at www.thrombosis-online.com . Note: This work was performed at the Medical University of Vienna, Austria. Schattauer GmbH 2017-06 2017-11-22 /pmc/articles/PMC6292180/ /pubmed/28692105 http://dx.doi.org/10.1160/TH17-03-0154 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.
spellingShingle Schoergenhofer, Christian
Hobl, Eva-Luise
Staudinger, Thomas
Speidl, Walter S.
Heinz, Gottfried
Siller-Matula, Jolanta
Zauner, Christian
Reiter, Birgit
Kubica, Jacek
Jilma, Bernd
Prasugrel in critically ill patients
title Prasugrel in critically ill patients
title_full Prasugrel in critically ill patients
title_fullStr Prasugrel in critically ill patients
title_full_unstemmed Prasugrel in critically ill patients
title_short Prasugrel in critically ill patients
title_sort prasugrel in critically ill patients
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292180/
https://www.ncbi.nlm.nih.gov/pubmed/28692105
http://dx.doi.org/10.1160/TH17-03-0154
work_keys_str_mv AT schoergenhoferchristian prasugrelincriticallyillpatients
AT hoblevaluise prasugrelincriticallyillpatients
AT staudingerthomas prasugrelincriticallyillpatients
AT speidlwalters prasugrelincriticallyillpatients
AT heinzgottfried prasugrelincriticallyillpatients
AT sillermatulajolanta prasugrelincriticallyillpatients
AT zaunerchristian prasugrelincriticallyillpatients
AT reiterbirgit prasugrelincriticallyillpatients
AT kubicajacek prasugrelincriticallyillpatients
AT jilmabernd prasugrelincriticallyillpatients