Atopaxar: A Review of Its Mechanism of Action and Role in Patients With Coronary Artery Disease

Abstract

Platelet activation and aggregation is a complex and key process in thrombus formation after the rupture of an atherosclerotic plaque, which can lead to an acute coronary syndrome. Aspirin, an irreversible inhibitor of thromboxane A₂ synthesis, in combination with an inhibitor of P2Y₁₂ ADP platelet receptors (clopidogrel, prasugrel or ticagrelor), represents the current standard of care of antiplatelet therapy for patients with acute coronary syndrome and in those patients undergoing percutaneous coronary intervention. Despite the benefit of these agents, the risk of thrombotic events and bleeding complications may still occur while on such antiplatelet treatment regimens, thus representing an important limitation. Thrombin is one of the most important platelet activators. The inhibition of thrombin-mediated platelet activation by means of protease-activated receptor-1 inhibitors represents an attractive therapeutic option for patients with atherothrombotic disease processes. This article provides an overview on atopaxar (E5555), an orally active protease-activated receptor-1 antagonist that has recently completed Phase II clinical investigation.

Keywords:

• acute coronary syndrome
• antiplatelet therapy
• atopaxar
• PAR-1 antagonist

Financial & competing interests disclosure

DJ Angiolillo reports receiving: honoraria for lectures from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly Co., Daiichi Sankyo Inc., AstraZeneca; consulting fees from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly Co., Daiichi Sankyo Inc., The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Abbott Vascular, AstraZeneca, Merck, Evolva; research grants from Bristol Myers Squibb, Sanofi-Aventis, GlaxoSmithKline, Otsuka, Eli Lilly Co., Daiichi Sankyo Inc., The Medicines Company, Portola; Accumetrics; Schering-Plough; AstraZeneca; Eisai. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.