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Published online: 2022-05-04

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The impact of mild therapeutic hypothermia on platelet reactivity in comatose survivors of cardiac arrest with acute myocardial infarction treated with ticagrelor

Julia M. Umińska1, Jakub Ratajczak2, Krzysztof Pstrągowski2, Katarzyna Buszko3, Klaudiusz Nadolny45, Tomasz Fabiszak2, Klemen Steblovnik6, Marko Noč6, Jacek Kubica2


Background: The aim of the study was to assess the antiplatelet effect of ticagrelor in patients with myocardial infarction (MI) after out-of-hospital cardiac arrest (OHCA) treated with percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) vs. MI patients without OHCA treated with PCI.

Methods: The study was designed and performed as a phase IV, single-center, investigator-initiated, prospective, observational study assessing the early pharmacodynamic effect (within first 24 h) of a ticagrelor loading dose (180 mg) in both groups of patients (MTH group vs. MI group). For assessment of ticagrelor pharmacodynamics Multiple Electrode Aggregometry (MEA) was applied.

Results: Compared with the MTH group, platelet inhibition was persistently stronger in the MI group over the entire observation period (up to 24 h), with the highest difference at 4 hours after loading with ticagrelor (25.8 ± 26.4 vs. 75.8 ± 40.9 U, p = 0.002). As a consequence, there was a higher prevalence of high platelet reactivity in the MTH group, with the most explicit difference at 6 hours after the loading dose of ticagrelor (78% vs. 7%, p < 0.001).

Conclusions: In comparison with patients treated with primary PCI for uncomplicated MI, the antiplatelet effect of ticagrelor in patients with MI complicated with OHCA, undergoing MTH and primary PCI, is attenuated and delayed.

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  1. Szczerbinski S, Ratajczak J, Lach P, et al. Epidemiology and chronobiology of out-of-hospital cardiac arrest in a subpopulation of southern Poland: a two-year observation. Cardiol J. 2020; 27(1): 16–24.
  2. Nadolny K, Bujak K, Kucap M, et al. The Silesian Registry of Out-of-Hospital Cardiac Arrest: study design and results of a three-month pilot study. Cardiol J. 2020; 27(5): 566–574.
  3. Szczerbiński S, Ratajczak J, Jasiewicz M, et al. Observational analysiS of out-of-hospital Cardiac Arrest occurRence and temporal variability patterns in subpopulation of southern POLand from 2006 to 2018: OSCAR-POL registry. Cardiol J. 2021 [Epub ahead of print].
  4. Borowicz A, Nadolny K, Bujak K, et al. Paramedic versus physician-staffed ambulances and prehospital delays in the management of patients with ST-segment elevation myocardial infarction. Cardiol J. 2021; 28(1): 110–117.
  5. Kubica J, Pstrągowski K, Adamski P, et al. Mild therapeutic hypothermia for patients with acute coronary syndrome and cardiac arrest treated with percutaneous coronary intervention (UNICORN). The design and rationale for the prospective, observational, multicenter study. Med Res J. 2016; 1(1): 23–27.
  6. Kołtowski Ł, Średniawa B, Tycińska A, et al. Predicting survival in out-of-hospital cardiac arrest patients undergoing targeted temperature management: The Polish Hypothermia Registry Risk Score. Cardiol J. 2021; 28(1): 95–100.
  7. Kubica J, Adamski P, Paciorek P, et al. Treatment of patients with acute coronary syndrome: recommendations for medical emergency teams: Focus on antiplatelet therapies. Updated experts' standpoint. Cardiol J. 2018; 25(3): 291–300.
  8. Gurbel PA, Myat A, Kubica J, et al. State of the art: oral antiplatelet therapy. JRSM Cardiovasc Dis. 2016; 5: 2048004016652514.
  9. Adamski P, Sikora J, Laskowska E, et al. Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study. PLoS One. 2017; 12(10): e0186013.
  10. Ostrowska M, Kubica J, Adamski P, et al. Stratified approaches to antiplatelet therapies based on platelet reactivity testing. Front Cardiovasc Med. 2019; 6: 176.
  11. Kubica J, Kubica A, Jilma B, et al. Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors. Int J Cardiol. 2016; 215: 201–208.
  12. Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016; 37(3): 245–252.
  13. Umińska J, Koziński M, Pstrągowski K, et al. Platelet reactivity during mild therapeutic hypothermia in patients with acute myocardial infarction treated with ticagrelor: study protocol of a single-centre study. Med Res J. 2017; 1(4): 115–119.
  14. Umińska JM, Ratajczak J, Buszko K, et al. Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest. Cardiol J. 2020; 27(6): 780–788.
  15. Ibrahim K, Christoph M, Schmeinck S, et al. High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation. 2014; 85(5): 649–656.
  16. Kander T, Dankiewicz J, Friberg H, et al. Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study. Crit Care. 2014; 18(5): 495.
  17. Schoergenhofer C, Hobl EL, Staudinger T, et al. Prasugrel in critically ill patients. Thromb Haemost. 2017; 117(8): 1582–1587.
  18. Penela D, Magaldi M, Fontanals J, et al. Hypothermia in acute coronary syndrome: brain salvage versus stent thrombosis? J Am Coll Cardiol. 2013; 61(6): 686–687.
  19. Tilemann LM, Stiepak J, Zelniker T, et al. Efficacy of enteral ticagrelor in hypothermic patients after out-of-hospital cardiac arrest. Clin Res Cardiol. 2016; 105(4): 332–340.
  20. Rosencher J, Gouffran G, Bougouin W, et al. Optimal antiplatelet therapy in out-hospital cardiac arrest patients treated by primary percutaneous coronary intervention. Resuscitation. 2015; 90: e7–e8.
  21. Jiménez-Brítez G, Freixa X, Flores-Umanzor E, et al. Out-of-hospital cardiac arrest and stent thrombosis: ticagrelor versus clopidogrel in patients with primary percutaneous coronary intervention under mild therapeutic hypothermia. Resuscitation. 2017; 114: 141–145.
  22. Bjelland TW, Hjertner Ø, Klepstad P, et al. Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation. 2010; 81(12): 1627–1631.
  23. Prüller F, Milke OL, Bis L, et al. Impaired aspirin-mediated platelet function inhibition in resuscitated patients with acute myocardial infarction treated with therapeutic hypothermia: a prospective, observational, non-randomized single-centre study. Ann Intensive Care. 2018; 8(1): 28.
  24. Bednar F, Kroupa J, Ondrakova M, et al. Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction. J Thromb Thrombolysis. 2016; 41(4): 549–555.
  25. Moudgil R, Al-Turbak H, Osborne C, et al. Superiority of ticagrelor over clopidogrel in patients after cardiac arrest undergoing therapeutic hypothermia. Can J Cardiol. 2014; 30(11): 1396–1399.
  26. Steblovnik K, Blinc A, Mijovski MB, et al. Ticagrelor versus clopidogrel in comatose survivors of out-of-hospital cardiac arrest undergoing percutaneous coronary intervention and hypothermia: a randomized study. Circulation. 2016; 134(25): 2128–2130.
  27. Tomala MT, Trąbka-Zawicki A, Machnik A, et al. Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia. Cardiol J. 2021 [Epub ahead of print].
  28. Kubica J, Kozinski M, Navarese EP, et al. Cangrelor: an emerging therapeutic option for patients with coronary artery disease. Curr Med Res Opin. 2014; 30(5): 813–828.
  29. Kubica A, Kozinski M, Navarese EP, et al. Intracoronary versus intravenous abciximab administration in STEMI patients: overview of current status and open questions. Curr Med Res Opin. 2011; 27(11): 2133–2144.
  30. Kubica J, Koziński M, Navarese EP, et al. Updated evidence on intracoronary abciximab in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials. Cardiol J. 2012; 19(3): 230–242.
  31. Navarese EP, Kozinski M, Obonska K, et al. Clinical efficacy and safety of intracoronary vs. intravenous abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention: a meta-analysis of randomized trials. Platelets. 2012; 23(4): 274–281.
  32. Siller-Matula JM, Specht S, Kubica J, et al. Abciximab as a bridging strategy to overcome morphine-prasugrel interaction in STEMI patients. Br J Clin Pharmacol. 2016; 82(5): 1343–1350.
  33. Tantry U, Chaudhary R, Kubica J, et al. Cangrelor for the treatment of patients with arterial thrombosis. Expert Opin Pharmacother. 2018; 19(12): 1389–1398.
  34. Adamski P, Koziński M, Ostrowska M, et al. Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors. Thromb Haemost. 2014; 112(2): 224–242.
  35. Adamski P, Adamska U, Ostrowska M, et al. New directions for pharmacotherapy in the treatment of acute coronary syndrome. Expert Opin Pharmacother. 2016; 17(17): 2291–2306.
  36. Adamski P, Adamska U, Ostrowska M, et al. Evaluating current and emerging antithrombotic therapy currently available for the treatment of acute coronary syndrome in geriatric populations. Expert Opin Pharmacother. 2018; 19(13): 1415–1425.