Platelet Adenosine Diphosphate P2Y12 Receptor Antagonism: Benefits and Limitations of Current Treatment Strategies and Future Directions

Platelet P2Y(12) receptor antagonism with clopidogrel has represented a major advancement in the pharmacological management of patients with atherothrombotic disease, in particular those with acute coronary syndromes and undergoing percutaneous coronary interventions. Despite the benefit associated with clopidogrel therapy in these high risk settings, laboratory and clinical experience have led to identify some of its caveats, among which its wide range of platelet inhibitory response is the most relevant. Genetic, cellular and clinical factors are implied in variability in response to clopidogrel. Importantly, pharmacodynamic findings have shown to have important prognostic implications, underscoring the need for more optimal antiplatelet treatment strategies. The aim of this manuscript is to provide an overview on the current status and future directions in P2Y(12) receptor antagonism, with particular emphasis on interindividual variability in response to clopidogrel and strategies, including novel antiplatelet agents, to improve platelet P2Y(12) inhibition.