Antiplatelet therapy: thrombin receptor antagonists

Authors

  • Antonio Tello-Montoliu,

    1. University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA
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  • Salvatore D. Tomasello,

    1. University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA
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  • Masafumi Ueno,

    1. University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA
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  • Dominick J. Angiolillo

    Corresponding author
      Dr Dominick J. Angiolillo MD, PhD, Department of Medicine, Division of Cardiology, University of Florida College of Medicine-Jacksonville, Shands Jacksonville Medical Center, 655 West 8th Street, Jacksonville, FL 32209, USA. Tel.: +1 904 244 3660, Fax: +1 904 244 3102, E-mail: dominick.angiolillo@jax.ufl.edu
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Dr Dominick J. Angiolillo MD, PhD, Department of Medicine, Division of Cardiology, University of Florida College of Medicine-Jacksonville, Shands Jacksonville Medical Center, 655 West 8th Street, Jacksonville, FL 32209, USA. Tel.: +1 904 244 3660, Fax: +1 904 244 3102, E-mail: dominick.angiolillo@jax.ufl.edu

Abstract

Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. Multiple pathways contribute to platelet activation. Aspirin, an irreversible inhibitor of thromboxane A2 synthesis, in combination with clopidogrel, an inhibitor of P2Y12 adenosine diphosphate platelet receptors, represent the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and for 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. Thrombin is one of the most important platelet activators. The inhibition of protease-activated receptor 1 showed a good safety profile in preclinical studies. In fact, phase II studies with vorapaxar (SCH530348) and atopaxar (E5555) showed no increase of bleeding events in addition to the current standard-of-care of antiplatelet therapy. Although the results of phase III trials for both drugs are awaited, this family is a promising new addition to the current clinical practice for patients with atherothrombotic disease, not only as an alternative, but also as additional therapy.

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