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Effects of vorapaxar on clot characteristics, coagulation, inflammation, and platelet and endothelial function in patients treated with mono‐ and dual‐antiplatelet therapy
Author(s) -
Bliden Kevin,
Chaudhary Rahul,
Kuliopulos Athan,
Tran Henry,
Taheri Hamid,
Tehrani Behnam,
Rosenblatt Arnold,
Navarese Eliano,
Tantry Udaya S.,
Gurbel Paul A.
Publication year - 2020
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14616
Subject(s) - medicine , von willebrand factor , platelet , fibrin , aspirin , clopidogrel , factor xiii , platelet activation , coagulation , fibrinogen , cardiology , anesthesia , pharmacology , immunology
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 B 2 (UTxB 2 ) 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 UTxB 2 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.