دورية أكاديمية
Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy.
| العنوان: | Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy. |
|---|---|
| المؤلفون: | 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; Lisa K. Jennings, PhD, 20 S. Dudley, Suite 900, Memphis, TN 38103, USA, Tel.: +1 901 866 1700, Fax: +1 901 866 1702, E-mail: ljennings@cirquestlabs.com. |
| المصدر: | Thrombosis and haemostasis [Thromb Haemost] 2014 May 05; Vol. 111 (5), pp. 883-91. Date of Electronic Publication: 2014 Jan 09. |
| نوع المنشور: | Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Thieme Country of Publication: Germany NLM ID: 7608063 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2567-689X (Electronic) Linking ISSN: 03406245 NLM ISO Abbreviation: Thromb Haemost Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2018- : Stuttgart : Thieme Original Publication: Stuttgart, Schattauer. |
| مواضيع طبية MeSH: | Acute Coronary Syndrome/*drug therapy , Blood Platelets/*drug effects , Lactones/*administration & dosage , Pyridines/*administration & dosage, Acute Coronary Syndrome/blood ; Adenosine Diphosphate/metabolism ; Aged ; Aspirin/administration & dosage ; Aspirin/adverse effects ; Biomarkers/blood ; Blood Platelets/physiology ; Cells, Cultured ; Europe ; Female ; Follow-Up Studies ; Humans ; Inflammation Mediators/blood ; Lactones/adverse effects ; Male ; Middle Aged ; North America ; Platelet Aggregation/drug effects ; Pyridines/adverse effects ; Receptor, PAR-1/antagonists & inhibitors ; Receptors, Thrombin/metabolism |
| مستخلص: | 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. |
| فهرسة مساهمة: | Keywords: Anti-platelet agents; PAR-1 receptor; pharmacodyamics; thienopyridines; vorapaxar |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Inflammation Mediators) 0 (Lactones) 0 (Pyridines) 0 (Receptor, PAR-1) 0 (Receptors, Thrombin) 0 (thienopyridine) 61D2G4IYVH (Adenosine Diphosphate) R16CO5Y76E (Aspirin) ZCE93644N2 (vorapaxar) |
| تواريخ الأحداث: | Date Created: 20140110 Date Completed: 20150416 Latest Revision: 20151119 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1160/TH13-07-0624 |
| PMID: | 24402559 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2567-689X |
|---|---|
| DOI: | 10.1160/TH13-07-0624 |