Pharmacogenomics and personalized medicine of the antiplatelet drugs

Abstract

Platelet activation and aggregation play a critical role in hemostasis and thrombosis. There is a fast-growing list of the antiplatelet drugs that are either marketed or under development, of which combination of aspirin and clopidogrel is now the standard of care for acute coronary syndromes or percutaneous coronary intervention for stenting. Overwhelming data have well demonstrated that aspirin monotherapy can greatly improve patient outcomes by irreversible suppression of the cyclooxygenase-1 enzyme responsible for the arachidonic acid pathway, that clopidogrel can exert its well-documented platelet inhibition through irreversible blockade of the platelet ADP receptor P2Y12, and that dual antiplatelet therapy (aspirin plus clopidogrel) is clinically more effective than either of the two for the secondary prevention of the recurrence of myocardial infarction, in-stent thrombosis, ischemic stroke, or even death. However, individuals may vary in their response to the drug, characterized by less or no response to either one or both in some patients when taking the same doses. It is well known that almost all genetic and nongenetic factors may contribute to that variation as summarized in this book chapter, and that DNA or pharmacogenomics is not the whole story about personalized medicine. The future landscape of optimal drug therapy would be much clearer over time and thus more attractive.