title: Protease-activated receptor-1 antagonists in long-term antiplatelet therapy. Current state of evidence and future perspectives.
abstract: Atherothrombosis and its clinical manifestations are among the leading causes of death in the developed world. The current standard-of-care antiplatelet therapy for the treatment of such events comprises aspirin and a thienopyridine or ticagrelor. However, recurrent ischemic events due to residual cardiovascular risk are a common phenomenon in these patients. It is believed that this residual risk is caused, at least in part, by thrombin, which signals through protease-activated receptors (PARs) and especially PAR-1. Thus, PAR-1 antagonism could represent an effective approach in the treatment of atherothrombotic disease. In this context, two potent and selective agents have been developed, vorapaxar and atopaxar. However, only vorapaxar has completed phase 3 clinical trials. In the present review, the main pharmacodynamic and pharmacokinetic properties of the PAR-1 antagonists are briefly described and the latest clinical data on vorapaxar are presented.
authors.affiliation: Atherothrombosis Research Center/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece.
authors.forename: I C
authors.initials: IC
authors.lastname: Moschonas
authors.affiliation: Department of Cardiology, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: J A
authors.initials: JA
authors.lastname: Goudevenos
authors.affiliation: Atherothrombosis Research Center/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece. Electronic address: atselep@uoi.gr.
authors.forename: A D
authors.initials: AD
authors.lastname: Tselepis
mesh_terms: D002986:Clinical Trials as Topic; D001026:Coronary Artery Bypass; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007097:Imines / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention; D058729:Peripheral Arterial Disease / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors; D015607:Stents / Q000009:adverse effects; D020521:Stroke / Q000139:chemically induced / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control
chemical_list: C540445:E 5555; D007097:Imines; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D018179:Receptors, Thrombin; C530299:vorapaxar
keywords: Myocardial infarction; Peripheral artery disease; Protease-activated receptor 1; Stent thrombosis; Stroke; Vorapaxar