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Thromb Haemost 2016; 116(06): 1140-1149
DOI: 10.1160/TH16-07-0535
New Technologies, Diagnostic Tools and Drugs
Schattauer Publishers Schattauer

Which platelet function test best reflects the in vivo plasma concentrations of ticagrelor and its active metabolite?

The HARMONIC study
Marek Koziński
1   Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Małgorzata Ostrowska
1   Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Piotr Adamski
1   Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Joanna Sikora
2   Department of Pharmacology and Therapy, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Adam Sikora
3   Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Aleksandra Karczmarska-Wódzka
2   Department of Pharmacology and Therapy, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Michat Piotr Marszał
1   Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Joanna Boinska
4   Department of Pathophysiology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Ewa Laskowska
1   Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Ewa Obońska
2   Department of Pharmacology and Therapy, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Tomasz Fabiszak
5   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Jacek Kubica
5   Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
› Author Affiliations Financial support: The HARMONIC study was supported by Collegium Medicum of Nicolaus Copernicus University (NCU CM grant no. 202) and did not receive any external funding.
Further Information

Publication History

Received 15 July 2016

Accepted after major revision: 24 August 2016

Publication Date:
09 March 2018 (online)

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Summary

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.

Study registration: ClinicalTrials.gov identifier NCT02690454.

Keywords

Ticagrelor - AR-C124910XX - flow cytometric VASP-assay - VerifyNow device - Multiplate analyzer

 

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