Pharmacogenetics of antithrombotic drugs

Antithrombotic therapy has improved the prognosis of patients with venous or arterial thrombosis. However, there is substantial interindividual variability in the response to antithrombotic drugs. This variability is due, in part, to genetics, which may affect the efficacy and safety of drugs used in the treatment and prevention of thrombosis. Pharmacogenetics studies the genetic factors related to interindividual variability in the response to drugs. Various polymorphisms in genes of the hemostatic system that have been reported to be markers of susceptibility to thromboembolic disease also seem to be implicated in the response to antithrombotic therapy. These include polymorphisms in platelet receptors (platelet glycoproteins) and coagulation factors (factors II, V, XII, XIII). There is also growing evidence on genetic polymorphisms affecting the metabolism (cytochrome P450), disposition, transporter proteins or cellular receptors of antithrombotic drugs. This review summarizes current knowledge on the pharmacogenetics of antithrombotic therapy, paying special attention to four therapeutic groups: antiplatelet agents, anticoagulants (vitamin K antagonists and heparin), fibrinolytics and other drugs used for the prevention of cardiovascular risk, such as statins and hormone replacement therapy in the menopause. The potential relevance of pharmacogenetics in the future of antithrombotic therapy and the design of clinical trials is also explored.