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dc.contributor.authorNilsen, Dennis W.T.
dc.contributor.authorRøysland, Michelle
dc.contributor.authorUeland, Thor
dc.contributor.authorAukrust, Pål
dc.contributor.authorMichelsen, Annika Elisabet
dc.contributor.authorStaines, Harry
dc.contributor.authorBarvik, Ståle
dc.contributor.authorKontny, Frederic
dc.contributor.authorNordrehaug, Jan Erik
dc.contributor.authorBonarjee, Vernon V S
dc.date.accessioned2023-02-02T15:05:30Z
dc.date.available2023-02-02T15:05:30Z
dc.date.issued2022-10-20
dc.description.abstractAbstract Background: Vorapaxar has been shown to reduce cardiovascular mortality in postmyocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. Aim: This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days’ FU and beyond, in patients with coronary heart disease. Methods: Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at–80°C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and -2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). Results: A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1-month FU (p ¼ 0.034). Angiopoietin-like 4 increased (p ¼ 0.028) and plasminogen activator inhibitor-2 decreased (p ¼ 0.025) in favor of vorapaxar at final FU. In postMI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p ¼ 0.029. Also, a short-term increase in von Willebrand factor (p ¼ 0.032) favoring vorapaxar was noted in NSTEMI patients. Conclusion: Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients.en_US
dc.identifier.citationNilsen DW, Røysland M, Ueland T, Aukrust P, Michelsen A, Staines H, Barvik S, Kontny F, Nordrehaug JE, Bonarjee VV. The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease. Thrombosis and Haemostasis. 2022en_US
dc.identifier.cristinIDFRIDAID 2119546
dc.identifier.doi10.1055/s-0042-1760256
dc.identifier.issn0340-6245
dc.identifier.urihttps://hdl.handle.net/10037/28471
dc.language.isoengen_US
dc.publisherThieme Gruppeen_US
dc.relation.journalThrombosis and Haemostasis
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)en_US
dc.titleThe Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Diseaseen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)