Effects of vorapaxar on clot characteristics, coagulation, inflammation, and platelet and endothelial function in patients treated with mono- and dual-antiplatelet therapy

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