Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions.
Platelet P2Y12 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 P2Y12 receptor antagonism, with particular emphasis on interindividual variability in response to clopidogrel and strategies, including novel antiplatelet agents, to improve platelet P2Y12 inhibition.
Angiolillo
Dominick J
DJ
University of Florida, College of Medicine-Jacksonville, Jacksonville, Florida 32209, USA. dominick.angiolillo@jax.ufl.edu
Ferreiro
José Luis
JL
D050197:Atherosclerosis / Q000188:drug therapy*; D000077144:Clopidogrel; D005544:Forecasting; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013927:Thrombosis / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine