title: Promises of PAR-1 inhibition in acute coronary syndrome.
abstract: Platelet activation is a key process in the pathogenesis of acute coronary syndromes (ACS). Of the many triggers involved in this process, three are presumed to be critical: thromboxane A(2) (TBXA(2)) via the TBXA(2) receptor, adenosine diphosphate via the P2Y(12) receptor, and thrombin via the protease-activated receptor (PAR)-1. Despite the effective inhibition of the first two pathways with aspirin and an expanding family of P2Y(12) inhibitors, the incidence of recurrent ischemic events remains high after ACS. PAR-1 inhibitors are a novel class of antiplatelet agents that inhibit thrombin-mediated platelet activation. Preclinical data and phase 2 clinical trials in patients with stable and unstable coronary disease support the potential of these compounds to improve clinical outcome. In this review we discuss the rationale for developing this novel class of agents with a focus on the two compounds in most advanced clinical development, vorapaxar (SCH 530348) and atopaxar (E5555).
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000473:pathology; D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007097:Imines / Q000627:therapeutic use*; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: C540445:E 5555; D007097:Imines; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D001241:Aspirin; C530299:vorapaxar