Department of Geriatric, Collegium Medicum, Nicolaus Copernicus University, Ul. M.Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Ul. M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
Cardiol J. 2020;27(6):780-788. doi: 10.5603/CJ.a2019.0024. Epub 2019 Feb 25.
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.
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.
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).
Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA.
ClinicalTrials.gov Identifier: NCT02611934.
院外心脏骤停（OHCA）常发生在急性心肌梗死（MI）的早期。幸存者需要经皮冠状动脉介入治疗（PCI），同时进行双联抗血小板治疗。对于复苏后的昏迷患者，应应用目标温度管理，包括亚低温（MTH）。然而，观察到低温患者支架血栓形成的风险增加。本研究旨在评估 MTH 对接受 MTH 和 PCI 治疗的 MI 后心脏骤停幸存者中替格瑞洛药代动力学的影响。
在一项前瞻性、观察性、单中心研究中，评估了 41 例 MI 患者（包括 11 例 OHCA 后接受 MTH 的患者（MTH 组）和 30 例无 OHCA 且未接受 MTH 的 MI 患者（非 MTH 组））的替格瑞洛药代动力学。在替格瑞洛 180mg 负荷剂量给药前、给药后 30 分钟、1、2、4、6、12 和 24 小时抽取血样。
在接受 MTH 治疗的患者中，负荷剂量后 12 小时内替格瑞洛的总暴露量和替格瑞洛的最大血浆浓度明显低于非 MTH 组（AUC（0-12）：3403 ± 2879 vs. 8746 ± 5596ng·h/mL，差异：61%，p = 0.01；Cmax：475 ± 353 vs. 1568 ± 784ng/mL，p = 0.0002）。替格瑞洛达到最大血浆浓度的时间也在 MTH 组延迟（替格瑞洛 tmax：12[6-24] vs. 4[2-12]h，p = 0.01）。
OHCA 后接受 MTH 治疗的 MI 患者替格瑞洛的生物利用度明显降低且延迟。
ClinicalTrials.gov 标识符：NCT02611934。
