Advances in antiplatelet therapy: overview of new P2Y12 receptor antagonists in development

Platelets play an important role in thrombus formation. A number of new antiplatelet agents currently in development are anticipated to improve clinical outcomes and safety benefits in patients with acute coronary syndrome (ACS). This manuscript reviews the pharmacology and clinical development of three of these agents: prasugrel, cangrelor, and AZD6140. Prasugrel, a third-generation, oral thienopyridine, has been shown to be superior to clopidogrel, the current gold standard, in preventing ischaemic events in patients with ACS undergoing percutaneous coronary intervention (PCI), although the bleeding rate was higher. Cangrelor, a chemical analogue of adenosine triphosphate, is a potent direct platelet P2Y12 antagonist. In development as an intravenous agent, cangrelor is currently being evaluated in two phase III studies in patients requiring PCI. AZD6140 is the first of a novel new class of antiplatelet agents that inhibits adenosine diphosphate-induced platelet aggregation at the level of the P2Y12 receptor. AZD6140 was shown to have a good safety profile in phase II studies and is currently being studied in a phase III trial in patients with ACS.