Antiplatelet therapy: thrombin receptor antagonists.

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 P2Y(12) 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.

• Authors: Antonio Tello-Montoliu, Salvatore D Tomasello, Masafumi Ueno, Dominick J Angiolillo
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 72 Issue 4 Pg. 658-71 (Oct 2011) ISSN: 1365-2125 [Electronic] England
• PMID: 21906120 (Publication Type: Journal Article, Review)
• Copyright: © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• E 5555
• Imines
• Lactones
• Platelet Aggregation Inhibitors
• Pyridines
• Receptors, Thrombin
• Aspirin
• vorapaxar

Topics

• Aspirin (therapeutic use)
• Blood Platelets (drug effects)
• Humans
• Imines (therapeutic use)
• Lactones (therapeutic use)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (therapeutic use)
• Pyridines (therapeutic use)
• Receptors, Thrombin (antagonists & inhibitors, therapeutic use)
• Thrombosis (drug therapy, prevention & control)