Julia M Umińska1, Jakub Ratajczak2, Katarzyna Buszko3, Przemysław Sobczak2, Wiktor Sroka4, Michał P Marszałł4, Piotr Adamski2, Klemen Steblovnik5, Marko Noč5, Jacek Kubica2. 1. Department of Geriatric, Collegium Medicum, Nicolaus Copernicus University, Ul. M.Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland. julia.m.kubica@gmail.com. 2. Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Ul. M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland. 3. Department of Theoretical Foundations of Biomedical Science and Medical Informatics, Collegium Medicum, Nicolaus Copernicus University, ul. Jagiellońska 13-15,, 85-067 Bydgoszcz, Poland. 4. Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Ul. M.Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland. 5. Ljubljana University Medical Centre, University of Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia.
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-center 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 a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose. RESULTS: In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the 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 the 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.
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 comatosepatients 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-center 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 a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose. RESULTS: In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the 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 the 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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