PAR-1 antagonists, including vorapaxar and atopaxar, offer a novel target for inhibiting platelet activation and aggregation, demonstrating a good safety profile in preliminary studies.
PAR-1 antagonists such as vorapaxar and atopaxar offer a novel target for antiplatelet therapy with promising early safety profiles, pending Phase III trial results.
IMPORTANCE OF THE FIELD: Aspirin, an irreversible inhibitor of thromboxane A(2) production, in combination with clopidogrel, an inhibitor of PY(12) 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.
Tomasello et al. (Thu,) conducted a review in Atherothrombotic events / Acute coronary syndrome. PAR-1 antagonists (vorapaxar and atopaxar) was evaluated. PAR-1 antagonists, including vorapaxar and atopaxar, offer a novel target for inhibiting platelet activation and aggregation, demonstrating a good safety profile in preliminary studies.