Pharmacogenetics of HMG-CoA Reductase Inhibitors: Optimizing the Prevention of Coronary Heart Disease

The statins are the most important group of drugs for lipid-lowering therapy in the prevention of coronary heart disease. Greater reductions in LDL-cholesterol appear to be associated with greater benefits but the clinical efficacy and safety of statin treatment varies considerably from person to person because of a combination of phenotypic and genotypic factors. Pharmacogenetic studies have investigated the relationship between common genetic variants and the lipid responses to statin therapy and adverse events, and some candidate genes related to the pharmacodynamics and pharmacokinetics of different statins have been identified. Some of these genetic variants show a different frequency in different ethnic groups. This field of pharmacogenetic research is receiving considerable attention and many new findings have been reported recently. Pharmacogenetic and pharmacogenomic studies of statin therapy are likely to provide a better understanding of the effects of these drugs and to help with prediction of the most appropriate drug and dosage for each individual and whether the addition or substitution of other lipid modifying drugs may be necessary to achieve the most safe and effective prevention of coronary heart disease.