Effects of vorapaxar on clot characteristics, coagulation, inflammation, and platelet and endothelial function in patients treated with mono‐ and dual‐antiplatelet therapy. (17th September 2019)

• Record Type: Journal Article
• Authors: Bliden, Kevin; Chaudhary, Rahul; Kuliopulos, Athan; Tran, Henry; Taheri, Hamid; Tehrani, Behnam; Rosenblatt, Arnold; Navarese, Eliano; Tantry, Udaya S.; Gurbel, Paul A.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 18:Number 1(2020)
• Page Start: 23
• Page End: 35
• Publication Date: 2019-09-17
• Subjects: aspirin -- clopidogrel -- endothelial function -- platelet aggregation -- vorapaxar; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.14616
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract: Background: Vorapaxar is indicated with standard antiplatelet therapy (APT) in patients with a history of myocardial infarction (MI) or peripheral arterial disease (PAD). Objectives: To evaluate the comparative effects of vorapaxar on platelet‐fibrin clot characteristics (PFCC), coagulation, inflammation, and platelet and endothelial function during treatment with daily 81 mg aspirin (A), 75 mg clopidogrel (C), both (C + A), or neither. Methods: Thrombelastography, conventional platelet aggregation (PA), ex vivo endothelial function by ENDOPAT, coagulation, platelet activation/inflammation marked by urinary 11‐dehydrothromboxane B2 (UTxB2 ) and safety were determined in patients who were APT naïve (n = 21), on C (n = 8), on A (n = 29), and on A + C (n = 23) during 1 month of vorapaxar therapy and 1 month of offset. Results: Vorapaxar had no effect on PFCC, ADP‐ or collagen‐induced PA, thrombin time, fibrinogen, PT, PTT, von Willebrand factor (vWF), D‐dimer, or endothelial function ( P > .05 in all groups). Inhibition of SFLLRN (PAR‐1 activating peptide)‐stimulated PA by vorapaxar was accelerated by A + C at 2 hours ( P < .05 versus other groups) with nearly complete inhibition by 30 days that persisted through 30 days after discontinuation in all groups ( P < .001). SFLLRN‐induced PA during offset was lower in APT patients versus APT‐naïve patients ( P < .05). Inhibition of UTxB2 was observed in APT‐naive patients treated with vorapaxar ( P < .05). Minor bleeding was only observed in C‐treated patients. Conclusion: Vorapaxar had no influence on PFCC measured by thrombelastography, coagulation, or endothelial function irrespective of APT. Inhibition of protease activated receptor (PAR)‐1 mediated platelet aggregation by vorapaxar was accelerated by A + C and offset was prolonged by concomitant APT. Vorapaxar‐induced anti‐inflammatory effects were observed in non‐aspirin‐treated patients.