Vorapaxar. PAR1 receptor antagonist, antiplatelet therapy

Atherothrombosis, including myocardial infarction and ischemic stroke, is a highly prevalent disease throughout the world. Platelet activation plays a crucial role in the onset of atherothrombotic events, while detailed mechanisms of platelet pathophysiology contributing to the onset of symptomatic atherothrombotic events have yet to be elucidated. Antiplatelet agents such as aspirin and clopidogrel are the most commonly used. Currently emerging agents exhibit certain limitations and are not capable of satisfactorily preventing the recurrence of atherothrombotic events without increasing the risk of serious bleeding. There are various receptors and activation signaling pathways in platelets, but aspirin and clopidogrel are specific inhibitors of cyclooxygenase COX-1 and the P2Y₁₂ receptor, respectively. Vorapaxar (Sch-530348) was developed as a specific inhibitor of the protease-activated receptor PAR1, which is entirely distinct from the previous antiplatelet agents. Results of phase II clinical trials with vorapaxar appear favorable for clinical practice, with a reasonably low rate of bleeding complications. Results of clinical outcome trials with a large enough sample size, along with detailed basic and translational research to further clarify the mechanism of action of vorapaxar, are eagerly awaited.