Pharmacogenomics of antiplatelet drugs

Abstract

Pharmacogenomics might contribute to the individual response variability to antiplatelet drugs (particularly aspirin and clopidogrel) in patients with ischemic coronary or cerebral vascular disease in terms of both therapeutic and adverse effects. Over the last two decades, a large number of studies and several meta-analyses on the possible genomic regulation of common "polygenic" ischemic cardio- and cerebrovascular diseases have been published. These studies have identified numerous DNA variants as disease or antiplatelet drug susceptibility markers. Some of these DNA variants confer a variable increase in risk for disease, while loss-of-function variants in the hepatic CYP2C19 system have been reported to be the predominant genetic mediators of clopidogrel and other thienopyridine drug antiplatelet response. However, the overall available data are still somewhat contradictory and do not yet allow to define a clear role for pharmacogenomics in providing effective, reliable, personalized antiplatelet therapy: neither clear conclusions nor definite guidelines are available on the clinical advantages of pharmacogenetic testing before prescribing antiplatelet drugs. In the near future, the relative role of additional rare polymorphisms, structural variants and tissue-specific epigenetic features of the human genome will hopefully be defined as significant contributors to the pathogenesis of cardio- and cerebrovascular disease and of individual patient's response to antiplatelet drugs.