Inhibiting PAR-1 in the prevention and treatment of atherothrombotic events

Importance of the field: Aspirin, an irreversible inhibitor of thromboxane A₂ production, in combination with clopidogrel, an inhibitor of PY₁₂ ADP platelet receptors, represents the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Although these agents have demonstrated significant clinical benefit, the increased risk of bleeding and the recurrence of thrombotic events represent substantial limitations.

Areas covered in this review: The inhibition of protease-activated receptors (PAR)-1, is the target for novel antiplatelet drugs, which showed a good safety profile in preclinical studies. The drugs most developed are vorapaxar (SCH530348) and atopaxar (E5555), which will be further evaluated in ongoing Phase III and II clinical trials respectively.

What the reader will gain: This review is focused on the current knowledge of PAR-1 antagonists, analyzing the pharmacological and early phase clinical investigation findings on these new drugs.

Take home message: The PAR-1 receptor offers a new target for the inhibition of platelet activation and aggregation. Preliminary results showed the good safety profile of these new agents. The results of the Phase III ongoing trials will provide important clinical insight into the blockade of thrombin-induced platelet activation.