Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel
Journal cover image

Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy.

Publication ,  Journal Article
Storey, RF; Kotha, J; Smyth, SS; Moliterno, DJ; Rorick, TL; Moccetti, T; Valgimigli, M; Dery, JP; Cornel, JH; Thomas, GS; Huber, K; Hord, E ...
Published in: Thrombosis and Haemostasis
May 2014

Vorapaxar is an antagonist of the protease activated receptor-1 (PAR-1), the principal platelet thrombin receptor. The Thrombin Receptor Antagonist for Clinical Event Reduction (TRACER) trial evaluated vorapaxar compared to placebo in non-ST-elevation (NSTE)-acute coronary syndrome (ACS) patients. It was the study's objective to assess the pharmacodynamic effects of vorapaxar versus placebo that included aspirin or a thienopyridine or, frequently, a combination of both agents in NSTE-ACS patients. In a substudy involving 249 patients, platelet aggregation was assessed by light transmittance aggregometry (LTA) in 85 subjects (41 placebo, 44 vorapaxar) using the agonists thrombin receptor activating peptide (TRAP, 15 μM), adenosine diphosphate (ADP, 20 μM), and the combination of collagen-related peptide (2.5 μg/ml) + ADP (5 μM) + TRAP (15 μM) (CAT). VerifyNow® IIb/IIIa and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assays were performed, and platelet PAR-1 expression, plasma platelet/endothelial and inflammatory biomarkers were determined before and during treatment. LTA responses to TRAP and CAT and VerifyNow results were markedly inhibited by vorapaxar. Maximal LTA response to TRAP (median, interquartile range) 2 hours post loading dose: placebo 68% (53-75%) and vorapaxar 3% (2-6%), p<0.0001. ADP inhibition was greater in the vorapaxar group at 4 hours and one month (p<0.01). In contrast to the placebo group, PAR-1 receptor number in the vorapaxar group at one month was significantly lower than the baseline (179 vs 225; p=0.004). There were significant changes in selected biomarker levels between the two treatment groups. In conclusion, vorapaxar caused a potent inhibition of PAR-1-mediated platelet aggregation. Further studies are needed to explore vorapaxar effect on P2Y12 inhibition, PAR-1 expression and biomarkers and its contribution to clinical outcomes.

Duke Scholars

Published In

Thrombosis and Haemostasis

DOI

EISSN

2567-689X

ISSN

0340-6245

Publication Date

May 2014

Volume

111

Issue

5

Start / End Page

883 / 891

Related Subject Headings

  • Receptors, Thrombin
  • Receptor, PAR-1
  • Pyridines
  • Platelet Aggregation
  • North America
  • Middle Aged
  • Male
  • Lactones
  • Inflammation Mediators
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Storey, R. F., Kotha, J., Smyth, S. S., Moliterno, D. J., Rorick, T. L., Moccetti, T., … Jennings, L. K. (2014). Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy. Thrombosis and Haemostasis, 111(5), 883–891. https://doi.org/10.1160/th13-07-0624
Storey, Robert F., Jayaprakash Kotha, Susan S. Smyth, David J. Moliterno, Tyrus L. Rorick, Tiziano Moccetti, Marco Valgimigli, et al. “Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy.Thrombosis and Haemostasis 111, no. 5 (May 2014): 883–91. https://doi.org/10.1160/th13-07-0624.
Storey RF, Kotha J, Smyth SS, Moliterno DJ, Rorick TL, Moccetti T, et al. Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy. Thrombosis and Haemostasis. 2014 May;111(5):883–91.
Storey, Robert F., et al. “Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy.Thrombosis and Haemostasis, vol. 111, no. 5, May 2014, pp. 883–91. Epmc, doi:10.1160/th13-07-0624.
Storey RF, Kotha J, Smyth SS, Moliterno DJ, Rorick TL, Moccetti T, Valgimigli M, Dery JP, Cornel JH, Thomas GS, Huber K, Harrington RA, Hord E, Judge HM, Chen E, Strony J, Mahaffey KW, Tricoci P, Becker RC, Jennings LK. Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy. Thrombosis and Haemostasis. 2014 May;111(5):883–891.
Journal cover image

Published In

Thrombosis and Haemostasis

DOI

EISSN

2567-689X

ISSN

0340-6245

Publication Date

May 2014

Volume

111

Issue

5

Start / End Page

883 / 891

Related Subject Headings

  • Receptors, Thrombin
  • Receptor, PAR-1
  • Pyridines
  • Platelet Aggregation
  • North America
  • Middle Aged
  • Male
  • Lactones
  • Inflammation Mediators
  • Humans