Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review

Abstract

Out‐of‐hospital cardiac arrest is among the most frequent causes of death worldwide. Immediate intervention, as well as dual antiplatelet therapy consisting of acetylsalicylic acid and a P2Y12 inhibitor is often recommended. In line with the growing number of reports on cardiac arrest treatment, therapeutic hypothermia (TH) has been proposed for unconscious patients to improve neurological outcomes. Nevertheless, studies report controversial and often discrepant results on the effect of hypothermia on blood coagulability and platelet reactivity. In this review, we summarize the knowledge on platelet function under diverse hypothermic conditions. Additionally, we review the current literature on the effect of systemic hypothermia on pharmacokinetic and pharmacodynamic properties of antiplatelet agents. It has been shown that TH can alter the effectiveness of antiplatelet agents, including P2Y12 inhibitors, through multiple mechanisms, hence, special attention should be paid while implementing antiplatelet therapy in patients under TH conditions.

Ticagrelor and prasugrel are independent predictors of improved long‐term survival in ACS patients

“…With increasing severity of the disease (STEMI > NSTEMI > unstable angina), the effect of clopidogrel decreased, which was demonstrated as elevated platelet reactivity in the MEA. These findings may be explained by HTPR on clopidogrel due to insufficient inhibition, occurring in about 20%‐30% of patients 37‐41 . Ticagrelor and prasugrel are superior to clopidogrel in reducing HTPR 42‐44 .…”

“…These findings may be explained by HTPR on clopidogrel due to insufficient inhibition, occurring in about 20%-30% of patients. [37][38][39][40][41] Ticagrelor and prasugrel are superior to clopidogrel in reducing HTPR. [42][43][44] HTPR on clopidogrel due to increasing severity of CAD would provide a possible explanation for the gradual rise in Long-term mortality 67 (10) 24 18) 20 (823 (7) .001…”

Role of P2Y Receptors in Platelet Extracellular Vesicle Release

“…The pleiotropic properties of P2Y12 inhibitors have been demonstrated in numerous studies and are summarized elsewhere [ 34 , 35 , 36 , 37 , 38 ]. These pleiotropic effects may be at least partly due to inhibition of PEV release.…”

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

“…Therefore, it is particularly important to assess the effectiveness of antiplatelet therapy in patients undergoing MTH after PCI. In this 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 [17][18][19][20][21]. The VerifyNow-P2Y12 (VN-P2Y12) test we used measures the extent of platelet aggregation in the presence of ticagrelor; its reliability in platelet aggregation assessment in patients with MTH has been previously established [19].…”