Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study

• Published in: PloS one Vol. 12; no. 10; p. e0186013
• Main Authors: Adamski, Piotr, Sikora, Joanna, Laskowska, Ewa, Buszko, Katarzyna, Ostrowska, Małgorzata, Umińska, Julia M., Sikora, Adam, Skibińska, Natalia, Sobczak, Przemysław, Adamska, Urszula, Rość, Danuta, Kubica, Aldona, Paciorek, Przemysław, Marszałł, Michał P., Navarese, Eliano P., Gorog, Diana A., Kubica, Jacek
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.10.2017; Public Library of Science (PLoS)
• Subjects: Adenosine - analogs & derivatives; Adenosine - blood; Adenosine - pharmacokinetics; Adenosine - pharmacology; Aged; Analysis; Bioavailability; Biological Availability; Biology and Life Sciences; Blood platelets; Blood Platelets - drug effects; Cardiology; Cardiovascular disease; Care and treatment; Chromatography; Clinical medicine; Complications and side effects; Coronary vessels; Dosage and administration; Drug dosages; Drug therapy; Electrocardiography; Female; Heart attack; Heart attacks; Humans; Internal medicine; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Medicine; Medicine and Health Sciences; Metabolites; Middle Aged; Myocardial infarction; Non-ST Elevated Myocardial Infarction - blood; Non-ST Elevated Myocardial Infarction - drug therapy; Patient outcomes; Patients; Pharmaceutical sciences; Pharmacodynamics; Pharmacokinetics; Pharmacology; Plasmas (physics); Platelet Aggregation Inhibitors - blood; Platelet Aggregation Inhibitors - pharmacokinetics; Prospective Studies; Purinergic P2Y Receptor Antagonists - pharmacokinetics; Purinergic P2Y Receptor Antagonists - pharmacology; ST Elevation Myocardial Infarction - blood; ST Elevation Myocardial Infarction - drug therapy; Thrombosis; Ticagrelor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186013

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