open access

Vol 1, No 4 (2016)
Original article
Published online: 2017-05-19
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Platelet reactivity during mild therapeutic hypothermia in patients with acute myocardial infarction treated with ticagrelor: study protocol of a single-centre study

Julia Maria Umińska1, Marek Koziński, Krzysztof Pstrągowski, Przemysław Paciorek, Tomasz Fabiszak, Joanna Sikora, Michał Marszałł, Grzegorz Grześk, Jacek Kubica
·
Medical Research Journal 2016;1(4):115-119.
Affiliations
  1. Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

open access

Vol 1, No 4 (2016)
ORIGINAL ARTICLES
Published online: 2017-05-19

Abstract

In summary, the available data on the antiplatelet efficacy of P2Y12 receptor inhibitors suggest their less potent and/or delayed effect in patients undergoing mild therapeutic hypothermia (MTH). However, previous studies do not explain the mechanisms of the impact of MTH on platelet function. Moreover, there is a lack of evidence of any relationship between the increased prevalence of thrombotic complications in MTH patients and the anti-platelet effect of P2Y12 receptor inhibitors.

We hypothesise that MTH may interfere with the absorption of ticagrelor and consequently results in significant changes in the pharmacokinetic and pharmacodynamic profile of this P2Y12 receptor inhibitor. It cannot be ruled out that the high initial level of platelet activation in MTH patients may additionally modify the pharmacodynamics of ticagrelor. Malabsorption may slow down the desired antiplatelet effect, while high levels of platelet activation may reduce the antiplatelet effect of ticagrelor.

The aim of this study is to verify whether the use of MTH after resuscitation in out-of-hospital cardiac arrest (OHCA) patients with STEMI (ST-segment elevation myocardial infarction) treated with primary percutaneous coronary intervention (pPCI), affects the anti-platelet effect of ticagrelor. Moreover, we attempt to elucidate the mechanisms of impaired effect of ticagrelor in MTH patients based on pharmacodynamic and pharmacokinetic measurements.

To achieve the aim of the study, we planned the following: 1) comparison of the pharmacokinetic and pharmacodynamic results obtained from the study population (MTH + pPCI + ticagrelor) with results obtained from a demographically and clinically comparable population of patients with STEMI treated with primary PCI and receiving ticagrelor (pPCI + ticagrelor); and 2) analysis of the pharmacodynamic results in relation to the pharmacokinetic measurements in the target population.

Understanding the mechanisms standing behind the impact of MTH on the efficacy of platelet inhibition with P2Y12 inhibitors is pivotal in reducing the risk of thrombotic complications. The study is expected to provide information leading to improvement of the safety of MTH in STEMI patients with OHCA treated with pPCI and receiving ticagrelor.

Abstract

In summary, the available data on the antiplatelet efficacy of P2Y12 receptor inhibitors suggest their less potent and/or delayed effect in patients undergoing mild therapeutic hypothermia (MTH). However, previous studies do not explain the mechanisms of the impact of MTH on platelet function. Moreover, there is a lack of evidence of any relationship between the increased prevalence of thrombotic complications in MTH patients and the anti-platelet effect of P2Y12 receptor inhibitors.

We hypothesise that MTH may interfere with the absorption of ticagrelor and consequently results in significant changes in the pharmacokinetic and pharmacodynamic profile of this P2Y12 receptor inhibitor. It cannot be ruled out that the high initial level of platelet activation in MTH patients may additionally modify the pharmacodynamics of ticagrelor. Malabsorption may slow down the desired antiplatelet effect, while high levels of platelet activation may reduce the antiplatelet effect of ticagrelor.

The aim of this study is to verify whether the use of MTH after resuscitation in out-of-hospital cardiac arrest (OHCA) patients with STEMI (ST-segment elevation myocardial infarction) treated with primary percutaneous coronary intervention (pPCI), affects the anti-platelet effect of ticagrelor. Moreover, we attempt to elucidate the mechanisms of impaired effect of ticagrelor in MTH patients based on pharmacodynamic and pharmacokinetic measurements.

To achieve the aim of the study, we planned the following: 1) comparison of the pharmacokinetic and pharmacodynamic results obtained from the study population (MTH + pPCI + ticagrelor) with results obtained from a demographically and clinically comparable population of patients with STEMI treated with primary PCI and receiving ticagrelor (pPCI + ticagrelor); and 2) analysis of the pharmacodynamic results in relation to the pharmacokinetic measurements in the target population.

Understanding the mechanisms standing behind the impact of MTH on the efficacy of platelet inhibition with P2Y12 inhibitors is pivotal in reducing the risk of thrombotic complications. The study is expected to provide information leading to improvement of the safety of MTH in STEMI patients with OHCA treated with pPCI and receiving ticagrelor.

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Keywords

platelet reactivity, ticagrelor, hypothermia

About this article
Title

Platelet reactivity during mild therapeutic hypothermia in patients with acute myocardial infarction treated with ticagrelor: study protocol of a single-centre study

Journal

Medical Research Journal

Issue

Vol 1, No 4 (2016)

Article type

Original article

Pages

115-119

Published online

2017-05-19

Page views

1155

Article views/downloads

896

DOI

10.5603/MRJ.2016.0021

Bibliographic record

Medical Research Journal 2016;1(4):115-119.

Keywords

platelet reactivity
ticagrelor
hypothermia

Authors

Julia Maria Umińska
Marek Koziński
Krzysztof Pstrągowski
Przemysław Paciorek
Tomasz Fabiszak
Joanna Sikora
Michał Marszałł
Grzegorz Grześk
Jacek Kubica

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