oronary syndrome (ACS) or elective PCI (six). In healthy folks, females had larger ticagrelor concentrations

oronary syndrome (ACS) or elective PCI (six). In healthy folks, females had larger ticagrelor concentrations than males after a single high dose ticagrelor (9). A equivalent efficacy and security profile of ticagrelor has been described in females and males with an ACS (10). Studies with regards to sex differences in pharmacodynamics and -kinetics of ticagrelor within the acute phase of STEMI are scarce. Within this sub-analysis from the ON-TIME three trial we examine sex differences in platelet inhibition and ticagrelor plasma concentrations inside the acute phase of STEMI.pharmacodynamics, were collected just before (T1) and straight away immediately after primary PCI (T2), and at 1-hour post-primary PCI (T3) and six hours post-primary PCI (T4). Pharmacodynamics were assessed by a VerifyNow P2Y12 point of care test (Accriva, San Diego, CA) for measurement of platelet reactivity units (PRU). Pharmacokinetics have been evaluated by determination of the ErbB4/HER4 Synonyms concentration of ticagrelor and its active metabolite, AR-C124910XX, utilizing liquid chromatography-mass spectrometry in the clinical chemistry laboratory in Zwolle.Study EndpointsThe major endpoint with the study was the level of platelet reactivity units (PRU) measured immediately post-primary PCI (T2). For the assessment from the main endpoint, blood was obtained just ahead of sheath removal in case of a principal PCI. Secondary endpoints included the level of PRU at other time points, Estrogen receptor Source higher on platelet reactivity (HPR) defined as PRU 208 (13) measured immediately post-primary PCI, the plasma concentrations of ticagrelor, its active metabolite as well as the cumulative plasma concentrations of ticagrelor and its active metabolite at all time points. Exploratory endpoints integrated main adverse cardiac events, including reinfarction, target vessel revascularization, stent thrombosis, death and BARC three and five bleeding (14), and all bleeding (BARC 1).Statistical AnalysisPatients have been analyzed as females vs. males. Continuous variables have been compared working with Student’s t-test and presented as imply and typical deviation (SD), or as median and interquartile range (IQR) and compared with Mann Whitney U test if they have been non-normally distributed. Categorical variables are presented as numbers and percentages and compared working with Pearson’s chi square test or Fisher exact test. Univariable and multivariable analyses have been performed for all endpoints. On top of that, a sensitivity evaluation utilizing various imputation for missing values was performed. Multivariate linear mixed effect modeling did not fulfill its assumptions. Therefore, we applied non-linear quantile regression methods for modeling of our data. Prospective confounders included in our analyses were age, study medication (IV acetaminophen or IV fentanyl), hypertension, renal function, platelet count and BMI. Within this evaluation the precise time immediately after randomization was utilized with time on a continuous scale. Bootstrapping was employed to establish the median differences and their self-confidence intervals in PRU or ticagrelor concentrations between each sexes at various timepoints. A p-value below 0.05 was thought of statistically important. All analyses have been performed with R version 3.6.0.Approaches Study Design and PatientsThe ON-TIME 3 trial was an investigator-initiated, randomized, open-label, multicenter study that randomized STEMI individuals, who had been pre-treated with aspirin and crushed ticagrelor, to fentanyl or acetaminophen iv within a pre-hospital setting. The main results showed greater absorption of ticagrelor with aceta