P4261Ticagrelor- and prasugrel-mediated platelet inhibition is not affected by mild therapeutic hypothermia generated in vitro in patients with an acute myocardial infarction

Abstract

Background: Mild hypothermia at 32‐34°C for 12‐24 hours is recommended by guidelines in comatose patients after cardiac arrest in addition to standard treatment, which includes antiplatelet therapy and percutaneous coronary intervention (PCI) in case of an acute myocardial infarction (AMI). Reduced responsiveness to clopidogrel has been reported under mild hypothermia conditions. However, the effect of hypothermia on platelet inhibition mediated by more potent P2Y12 inhibitors, such as ticagrelor and prasugrel, has not been fully elucidated. Purpose: To evaluate the effect of mild hypothermia induced in vitro on platelet inhibition in AMI patients treated with ticagrelor or prasugrel. Methods: Prospective in vitro pharmacodynamic (PD) study with paired data conducted in AMI patients undergoing PCI that received dual antiplatelet therapy with aspirin and ticagrelor or aspirin and prasugrel as per clinical indication. Venous samples from each patient were extracted within 24 hours after PCI and placed in two separate waterbaths, one of them previously warmed at 37 °C and other at 33 °C. After incubation for one hour, platelet function tests were performed, including: a) Multiple electrode aggregometry (MEA) using ADP as agonist, defining high on‐treatment platelet reactivity (HTPR) as >468 AU∗min; and b) VerifyNow (VN) P2Y12 assay, defining HTPR as >208 P2Y12 reaction units (PRU). Comparisons between platelet reactivity at 37°C and 33°C were performed with ANOVA for repeated measures using a general linear model. Results: Forty patients were recruited, 20 treated with ticagrelor and 20 treated with prasugrel. One poor‐quality sample had to be discarded in ticagrelor group, thus, 39 patients with complete PD data were included in the analysis. No significant differences in platelet reactivity between samples at 37°C or 33°C were observed in patients treated with ticagrelor with either MEA (156.2±20 vs. 131.2±16.2 AU∗min; p=0.067 [Figure, panel A]) or VN (48.5±15.8 vs. 40.3±13.8 PRU; p=0.074). Likewise, no differences were found in samples of patients treated with prasugrel when analyzed with MEA (97.6±7.75 vs. 99.1±8.57 AU∗min; p=0.852 [Figure, panel B]) or VN (26.5±9.43 vs. 24.2±9.6 PRU; p=0.374). No patient treated with either ticagrelor or prasugrel had HTPR at 37°C or 33°C. Conclusions: Mild therapeutic hypothermia generated in vitro has no significant impact on platelet response to potent P2Y12 inhibitors, such as ticagrelor and prasugrel, in AMI patients. Ex vivo studies are warranted in order to confirm these findings.