University of Hertfordshire

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Documents

  • Piotr Adamski
  • Joanna Sikora
  • Ewa Laskowska
  • Katarzyna Buszko
  • Małgorzata Ostrowska
  • Julia M Umińska
  • Adam Sikora
  • Natalia Skibińska
  • Przemysław Sobczak
  • Urszula Adamska
  • Danuta Rość
  • Aldona Kubica
  • Przemysław Paciorek
  • Michał P Marszałł
  • Eliano P Navarese
  • Diana A Gorog
  • Jacek Kubica
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Original languageEnglish
Article numbere0186013
Number of pages12
JournalPLoS ONE
Volume12
Issue10
DOIs
Publication statusPublished - 12 Oct 2017

Abstract

BACKGROUND: Data from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI) may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI).

METHODS: In a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24) underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX) plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry.

RESULTS: During the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0-6): 2491 [344-5587] vs. 3991 [1406-9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0-6): 473 [0-924] vs. 712 [346-1616] ng*h/mL; p = 0.027). STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0-12.0] vs. 2.5 [2.0-6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment.

CONCLUSIONS: Plasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015).

Notes

© 2017 Adamski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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