Abstract
Platelet activation and aggregation play important roles in ischemic event occurrences in patients with coronary artery disease. In the absence of a disease state and drug administration, platelet reactivity has been shown to be stable over time, indicating a high level of heritability. Interindividual variability in platelet response to agonists and in response to aspirin and clopidogrel administration along with the influence of different single nucleotide polymorphisms on platelet reactivity based on candidate gene and genome-wide association studies have been demonstrated in healthy subjects. Reduced pharmacodynamic effect and reduced clinical efficacy of clopidogrel have been well documented in high-risk coronary artery disease patients carrying a loss-of-function allele of the CYP2C19 gene. These factors are recognized by the recent American and European treatment guidelines. However, prasugrel and ticagrelor are associated with superior and predictable pharmacodynamic responses and better clinical outcomes compared with clopidogrel.
Financial & competing interests disclosure
This work was supported by Sinai Center for Thrombosis Research. US Tantry has received payment for lectures and travel support from Accumetrics. YH Jeong has received honoraria for lectures from sanofi-aventis, Daiichi Sankyo Inc. and Otsuka. PA Gurbel has served as a consultant for Daiichi Sankyo Inc., Lilly, Pozen, Novartis, Bayer, AstraZeneca, Accumetrics, Nanosphere, Sanofi-Aventis, Boehringer Ingelheim, Merck, Medtronic, Iverson Genetics, CSL and Haemonetics, and receiving grants from the NIH, Daiichi Sankyo Inc., Lilly, Pozen, CSL, AstraZeneca Haemoscope, Medtronic, Harvard Clinical Research Institute and Duke Clinical Research Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
AstraZeneca provided limited editorial assistance for the preparation of this manuscript.