Pharmacogenetics of antiplatelet therapy: ready for clinical application?

Pharmacogenetics has many possible applications in the drug treatment of cardiovascular diseases. First, individual patients may be screened for genetic polymorphisms to choose agents with the greatest potential for efficacy and least potential for toxicity. Second, pharmacogenetics may be useful for dose adaptations for specific drugs in patients with aberrant drug metabolism. Based on the annual report of the American Heart Association, in 2010, an estimated 785 000 Americans will have a new coronary attack and 610 000 people will experience a new stroke. Despite the advances in the development of more potent platelet inhibitors and more precise revascularisation techniques, 470 000 recurrent coronary attacks and 185 000 recurrent strokes are expected, indicating that optimisation of treatment strategies is warranted.w1 The large number of pharmacogenetic studies undertaken in recent years may provide enough evidence to aid clinicians in prescribing the most optimal drug in the proper concentration in the individual patient. This article discusses the current knowledge of pharmacogenetics of antiplatelet drugs. Human blood platelets are essential and hazardous at the same time. They are, on the one hand, indispensable for appropriate haemostasis upon vascular injury, but, on the other hand, play a major role in the pathophysiology of thrombosis. Since thrombosis of atherosclerotic plaques is the most frequent cause of myocardial ischaemia and embolic stroke, antiplatelet therapy is the cornerstone of modern cardiovascular treatment, as it has been implemented in all major guidelines. It is well known that not all patients derive the same degree of benefit from antiplatelet treatment. Individual differences in the intrinsic rate of platelet reactivity and a wide variability in response to antiplatelet therapy causes a considerable number of patients (up to 25%)1 to be non-responsive and continue to experience new thrombotic events despite guideline treatment. In the literature regarding the pharmacogenetics of platelet inhibitors, the term …