New developments in antiplatelet therapy

Abstract

The P2Y12 receptor plays a central role in platelet aggregation, and the clinical effectiveness of the thienopyridine clopidogrel, an irreversible P2Y12 antagonist, in preventing thrombosis provides proof that P2Y12 blockade is a sound strategy in reducing thrombotic risk. Drawbacks of clopidogrel treatment include prolonged time to onset and offset of effect and a variable inhibition of platelet aggregation (IPA). New P2Y12 antagonists have been developed to overcome these drawbacks. Prasugrel is a new thienopyridine that is more efficiently metabolized to its active form than clopidogrel, providing more rapid onset of effect and greater and more consistent IPA. AZD6140 is a reversible oral P2Y12 antagonist that does not require metabolic activation. AZD6140 provides more rapid onset and offset of effect than clopidogrel and greater and more consistent IPA, with a level of IPA depending on plasma drug concentrations. Cangrelor is a direct, reversible intravenous P2Y12 antagonist that has rapid onset and offset of action. Phase 2 trials of these agents have provided some evidence of potential clinical benefits in patients at risk of thrombotic events. Recent and ongoing Phase 3 trials will provide important information on how to improve clinical outcomes with P2Y12 inhibition: the TRITON-TIMI 38 trial comparing prasugrel with clopidogrel in 13 608 patients with acute coronary syndromes (ACS) and planned percutaneous coronary intervention (PCI); the PLATO trial comparing AZD6140 with clopidogrel in approximately 18 000 patients with ACS undergoing medical management, PCI, or coronary artery bypass grafting; and the CHAMPION PCI trial of cangrelor vs. clopidogrel in patients with ACS or stable coronary disease undergoing PCI.