Key result
Mild therapeutic hypothermia significantly decreased the total exposure to ticagrelor by 61% during the first 12 hours in patients with acute myocardial infarction after out-of-hospital cardiac arrest.
Why the study?
Stent thrombosis risk is increased in patients undergoing hypothermia, prompting assessment of the impact of mild therapeutic hypothermia on the pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with PCI.
Does mild therapeutic hypothermia affect the bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest?
Observational (n=41)
No
Does mild therapeutic hypothermia affect the bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest?
Absolute Event Rate: 3403% vs 8746%
p-value: p=0.01
Mild therapeutic hypothermia significantly decreases and delays the bioavailability of ticagrelor in MI patients after out-of-hospital cardiac arrest, which may explain the increased risk of stent thrombosis in this population.
May reduce ticagrelor efficacy in hypothermic post-arrest MI patients; hypothesis-generating for adjusted dosing or alternatives to lower thrombosis risk.
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.
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Umińska et al. (2019) conducted an observational in Acute myocardial infarction after out-of-hospital cardiac arrest (n=41). Mild therapeutic hypothermia (MTH) vs. No mild therapeutic hypothermia (no-MTH) was evaluated on Area under the plasma concentration-time curve (AUC(0-12)) for ticagrelor during the first 12 hours after loading dose (p=0.01). Mild therapeutic hypothermia significantly decreased the total exposure to ticagrelor by 61% during the first 12 hours in patients with acute myocardial infarction after out-of-hospital cardiac arrest.
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