Platelet P2Y₁₂ receptor inhibition: an update on clinical drug development

Antiplatelet therapy is the cornerstone of treatment for patients with coronary artery disease. Since adenosine diphosphate (ADP) represents one of the most important mediators of thrombosis, the inhibition of the platelet ADP receptor, in particular the P2Y₁₂ subtype, plays a pivotal role in secondary prevention of recurrent atherothrombotic events in high-risk settings. Numerous clinical trials have shown the efficacy of clopidogrel, an inhibitor of the ADP P2Y₁₂ receptor, in patients presenting with an acute coronary syndrome and undergoing percutaneous coronary intervention. However, laboratory and clinical experience with clopidogrel have led to understanding some of the limitations of this drug, the most important of which is its broad range in interindividual response variability, resulting in the development of novel ADP P2Y₁₂ receptor-inhibiting strategies. This article provides an overview of ADP P2Y₁₂ receptor-inhibiting strategies, including high clopidogrel dosing regimens and novel agents under advanced clinical development.