Platelet thrombin receptor antagonism with vorapaxar: pharmacology and clinical trial development

Oral antiplatelet therapies for secondary prevention of ischemic recurrences in patients with atherosclerotic disease manifestations include aspirin and P2Y12 receptor antagonists. Despite the use of these therapies, patients remain at risk for recurrent ischemic events, which may be attributed to other platelet signaling pathways which continue to be activated. More intense antithrombotic strategies have been investigated, including identifying additional targets to modulate platelet activation. Among these, thrombin-mediated platelet activation through PAR-1 has been subject to broad clinical investigation. Vorapaxar is the only PAR-1 receptor antagonists that completed large-scale clinical investigations and is approved for clinical use. This manuscript provides an overview of the pharmacology and clinical trial development of vorapaxar as well as its role in clinical practice.