Cardiovascular Pharmacogenomics: An Update on Clinical Studies of Antithrombotic Drugs in Brazilian Patients

AbstractAnticoagulant and antiplatelet drugs effectively prevent thrombotic events in patients with cardiovascular diseases, ischemic stroke, peripheral vascular diseases, and other thromboembolic diseases. However, genetic and non-genetic factors affect the response to antithrombotic therapy and can increase the risk of adverse events. This narrative review discusses pharmacogenomic studies on antithrombotic drugs commonly prescribed in Brazil. Multiple Brazilian studies assessed the impact of pharmacokinetic (PK) and pharmacodynamic (PD) gene variants on warfarin response. The reduced function allelesCYP2C9*2 andCYP2C9*3, andVKORC1 rs9923231 (c.-1639G>A) are associated with increased sensitivity to warfarin and a low dose requirement to prevent bleeding episodes, whereasCYP4F2 rs2108622 (p.Val433Met) carriers have higher dose requirements (warfarin resistance). These deleterious variants and non-genetic factors (age, gender, body weight, co-administered drugs, food interactions, and others) account for up to 63% of the warfarin dose variability. Few pharmacogenomics studies have explored antiplatelet drugs in Brazilian cohorts, finding associations betweenCYP2C19*2,PON1 rs662 andABCC3 rs757421 genotypes and platelet responsiveness or clopidogrel PK in subjects with coronary artery disease (CAD) or acute coronary syndrome (ACS), whereasITGB3 contributes to aspirin PK but not platelet responsiveness in diabetic patients. Brazilian guidelines on anticoagulants and antiplat...
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research