Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia

Abstract

Background: Mild therapeutic hypothermia (MTH) is believed to reduce the effectiveness of antiplatelet drugs. Effective dual-antiplatelet therapy after percutaneous coronary intervention (PCI) is mandatory to avoid acute stent thrombosis (ST). The effectiveness of ticagrelor in MTH-treated out-of-hospital cardiac arrest (OHCA) survivors is still a matter of debate. The aim of the study was to evaluate the impact of MTH on the platelet-inhibitory effect of ticagrelor in comatose survivors of OHCA treated with primary PCI.Methods: Eighteen comatose survivors of OHCA with acute coronary syndrome undergoing immediate PCI treated with MTH were compared with 14 patients with uncomplicated primary myocardial infarction after PCI, matched for gender and age, in a prospective, single-center, observational study. Platelet aggregation was evaluated using VerifyNow P2Y12 pointof-care testing at 3 time points: admission (T0), during MTH (T1), and 48-72 h after rewarming (T2).Results: Ticagrelor effectively inhibits platelet aggregation in OHCA patients subjected to MTH and in all patients in the control group. The effectiveness of ticagrelor did not differ between the MTH group and the control group (p = 0.581). In 2 cases in the MTH population, the platelet response to ticagrelor was inadequate, and in one of them it remained insufficient during the re-warming phase. There was no stent thrombosis in these patients. Conclusions:The present study confirmed the effectiveness of ticagrelor to inhibit platelets in myocardial infarction patients after OHCA treated with primary PCI undergoing hypothermia. The use of cooling was not associated with an increased risk of stent thrombosis.

Does ticagrelor effectively inhibit platelets in patients undergoing mild therapeutic hypothermia or it does not?

“…Tomala et al [32] reported similar findings for a time range of 12-24 hours, however in this team's observation the difference disappeared 48-72 hours after loading. This finding led the authors to a conclusion quite different from one reached by Tomala et al [33] and Umińska et al [34]. The analysis of the methods and results of both studies shows, however, that despite different conclusions, both studies are consistent, and moreover, they complement each other.…”

“…Recently, two pharmacokinetic studies with seemingly contradictory conclusions appeared in the “Cardiology Journal”. First, Tomala et al [ 33 ] confirms the effectiveness of ticagrelor to inhibit platelets in MI patients after OHCA treated with pPCI undergoing hypothermia. The other, by Umińska et al [ 34 ], states that the antiplatelet effect of ticagrelor is attenuated and delayed in MI patients undergoing MTH and pPCI due to OHCA, in comparison with patients treated with pPCI for uncomplicated MI.…”

“…The other, by Umińska et al [ 34 ], states that the antiplatelet effect of ticagrelor is attenuated and delayed in MI patients undergoing MTH and pPCI due to OHCA, in comparison with patients treated with pPCI for uncomplicated MI. As stressed in the first publication, in this clinical setting ticagrelor should be the drug of choice before clopidogrel due to its better absorption, faster metabolism, quicker onset of action, and its lack of requirement for metabolic activation [ 33 ]. However, in the previously published study [ 25 ], impaired bioavailability of ticagrelor and delayed maximal plasma concentration of the drug in patients undergoing MTH and pPCI due to OHCA were demonstrated.…”

Pre-hospital treatment of patients with acute coronary syndrome: Recommendations for medical emergency teams. Expert position update 2022

“…Due to its rapid onset of action cangrelor appears to be the optimal P2Y12 receptor inhibitor for ACS patients requiring urgent invasive treatment [44,45]. This compound may be considered in patients not pre-treated with oral P2Y12 receptor inhibitors at the time of PCI or in those who are considered unable to absorb oral agents, particularly in unconscious patients, patients with post-cardiac arrest syndrome, or patients treated with mild therapeutic hypothermia, when gastrointestinal absorption of medications is impaired [2,5,[46][47][48]. Unfortunately, up to date cangrelor is not available in Poland.…”

Opioids and oral P2Y12 receptor inhibitors: A drug–drug interaction

“…The PERSEUS study, however, does not provide a comparison with any non-opioid treatment strategy, making it impossible to truly assess the effects of fentanyl on the pharmacokinetics and pharmacodynamics of ticagrelor in AMI patients. In this specific clinical setting, despite opioid-induced decreased bioavailability of P2Y12 receptor inhibitors, some additional factors, including enhanced platelet activation and reduced gastrointestinal perfusion as well as impact of mild therapeutic hypothermia applied in cardiac arrest survivors, may also impede the effect of oral antiplatelet drugs [18][19][20][21][22][23][24].…”