Pharmacogenetics and pharmacogenomics of cholesterol-lowering therapy

Abstract

To summarize recent findings on pharmacokinetics, pharmacodynamics, drug–drug interactions and influence of lifestyle heterogeneity on adverse events in cholesterol-lowering therapy The prevention of cardiovascular disease is critically dependent on lipid-lowery therapy, including statins, cholesterol absorption inhibitors, fibrates and nicotinic acid. Statins are the most prescribed drugs in lipid lowering therapy with variability in response and almost one third of the patients do not meet their treatment goals. The severe adverse effects of treatment with cerivastatin stimulated the search for new genes and gene variations affecting pharmacokinetics, drug–drug interactions and pharmacodynamics. Moreover, instead of monotherapy, combined therapy of statins with ezetemibe and niacin was considered. This led to the identification of CD13, NPC1L1 and HM74A as new targets and CYP2C8 and glucuronidation enzymes as potential targets for drug–drug interactions. Moreover multiple polymorphic sites and pleiotrophic gene targets were reinvestigated in larger cohorts and the relevant pathogenetic factors start to evolve. Statin therapy is widely used and well tolerated by the majority of patients. To further reduce potential adverse effects and to increase efficacy, combined therapy concepts with ezetimibe or niacin are underway.