Cardiovascular Pharmacogenomics: Expectations and Practical Benefits

Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Pharmacogenomics is the study of genetic determinants of interindividual variation in drug response and aims to facilitate personalized medicine, through genotype-informed drug and dose selection, to maximize drug efficacy and/or minimize adverse drug reactions. Despite high expectations, no cardiovascular pharmacogenomic association is currently in widespread clinical practice; evidential, logistical, financial, and knowledge implementation barriers exist. Nevertheless, VKORC1, CYP2C9, and CYP4F2 variants have been associated with warfarin dose requirements, and CYP2C19 variants have been associated with perturbed antiplatelet response to clopidogrel. However, at present, controversy exists over the clinical utility of these genetic associations. There is an increased risk of simvastatin-induced muscle toxicity in SLCO1B1*5 carriers, ADRB1 and ADRA2C polymorphisms are associated with differential response to bucindolol, and rare congenital arrhythmia gene variants have been identified in drug-induced torsade de pointes. Practical benefits are still anticipated, but much work remains.