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Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest

Julia Maria Umińska, Jakub Ratajczak, Katarzyna Buszko, Przemysław Sobczak, Wiktor Sroka, Michał Piotr Marszałł, Piotr Adamski, Klemen Steblovnik, Marko Noč, Jacek Kubica
DOI: 10.5603/CJ.a2019.0024
·
Pubmed: 30799546

open access

Ahead of print
Original articles
Published online: 2019-02-20

Abstract

Background: Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI. Methods: In a prospective, observational, single-centre study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a180 mg ticagrelor loading dose, and 30 minutes, 1, 2, 4, 6, 12, and 24 hours after the loading dose. Results: In patients treated with MTH total exposure to ticagrelor during the first 12 hours after the loading dose  and maximal plasma concentration of ticagrelor  were significantly lower than in no-MTH group (AUC(0–12): 3403±2879 vs. 8746±5596 ng·h/mL, difference: 61%, p=0.01; Cmax: 475±353 vs. 1568±784 ng/mL, p=0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p=0.01). Conclusions: Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. Trial registration: ClinicalTrials.gov Identifier: NCT02611934

Abstract

Background: Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI. Methods: In a prospective, observational, single-centre study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a180 mg ticagrelor loading dose, and 30 minutes, 1, 2, 4, 6, 12, and 24 hours after the loading dose. Results: In patients treated with MTH total exposure to ticagrelor during the first 12 hours after the loading dose  and maximal plasma concentration of ticagrelor  were significantly lower than in no-MTH group (AUC(0–12): 3403±2879 vs. 8746±5596 ng·h/mL, difference: 61%, p=0.01; Cmax: 475±353 vs. 1568±784 ng/mL, p=0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p=0.01). Conclusions: Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. Trial registration: ClinicalTrials.gov Identifier: NCT02611934

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Keywords

cardiac arrest, myocardial infarction, hypothermia, ticagrelor, pharmacokinetics, platelets

About this article
Title

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest

Journal

Cardiology Journal

Issue

Ahead of print

Published online

2019-02-20

DOI

10.5603/CJ.a2019.0024

Pubmed

30799546

Keywords

cardiac arrest
myocardial infarction
hypothermia
ticagrelor
pharmacokinetics
platelets

Authors

Julia Maria Umińska
Jakub Ratajczak
Katarzyna Buszko
Przemysław Sobczak
Wiktor Sroka
Michał Piotr Marszałł
Piotr Adamski
Klemen Steblovnik
Marko Noč
Jacek Kubica

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