title: Which platelet function test best reflects the in vivo plasma concentrations of ticagrelor and its active metabolite? The HARMONIC study.
abstract: Aim of this study was assessment of the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of selected platelet function tests. In a single-centre, cohort study, patients with myocardial infarction underwent blood sampling following a 180 mg ticagrelor loading dose intake (predose, 1, 2, 3, 4, 6, 12, 24 hours postdose) to perform pharmacokinetic and pharmacodynamic assessments. Platelet reactivity was evaluated using the VASP-assay, the VerifyNow device and the Multiplate analyzer. Analysis of 36 patients revealed high negative correlations between ticagrelor concentrations and platelet reactivity evaluated with all three platelet function tests (the VASP-assay: RS=-0.722; p<0.0001; the VerifyNow device: RS=-0.715; p<0.0001; the Multiplate analyzer: RS=-0.722; p<0.0001), with no significant differences between correlation coefficients. Similar results were found for AR-C124910XX. Platelet reactivity values assessed with all three methods generally correlated well with each other; however, a significantly higher correlation (p<0.02) was demonstrated between the VerifyNow and Multiplate tests (RS=0.707; p<0.0001) than in other assay combinations (the VASP-assay and the VerifyNow device: RS=0.595; p<0.0001; the VASP-assay and the Multiplate analyzer: RS=0.588; p<0.0001). With respect to the recognition of high platelet reactivity, we found higher measurement concordance between the VerifyNow and Multiplate tests compared with other assay combinations, while for low platelet reactivity, only results of the VerifyNow and Multiplate assay were related to each other. Platelet reactivity measurements performed with the VASP, VerifyNow and Multiplate tests show comparably strong negative correlations with ticagrelor and AR-C124910XX concentrations.
authors.affiliation: Marek Koziński, Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, 9 Skłodowskiej-Curie Street, Bydgoszcz 85-094, Poland, Tel.: +48 52 5854023, Fax: +48 52 5854024, E-mail: marekkozinski@wp.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Koziński
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Ostrowska
authors.forename: Piotr
authors.initials: P
authors.lastname: Adamski
authors.forename: Joanna
authors.initials: J
authors.lastname: Sikora
authors.forename: Adam
authors.initials: A
authors.lastname: Sikora
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Karczmarska-Wódzka
authors.forename: Michał Piotr
authors.initials: MP
authors.lastname: Marszałł
authors.forename: Joanna
authors.initials: J
authors.lastname: Boinska
authors.forename: Ewa
authors.initials: E
authors.lastname: Laskowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Obońska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Fabiszak
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D010979:Platelet Function Tests / Q000379:methods*; D011446:Prospective Studies; D000077486:Ticagrelor; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077486:Ticagrelor; D000241:Adenosine
keywords: AR-C124910XX; Multiplate analyzer; Ticagrelor; VerifyNow device; flow cytometric VASP-assay