Advances in the management of dyslipidemia.

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in the United States and therapies aimed at lipid modification are important for the reduction of cardiovascular risk. There have been many exciting advances in lipid management over the recent years. This review discusses these recent advances as well as the direction of future studies. Several recent clinical trials support low-density lipoprotein cholesterol (LDL-c) reduction beyond maximal statin therapy for improved cardiovascular outcomes. Ezetimibe reduced LDL-c beyond maximal statin therapy and was associated with improved cardiovascular outcomes for high-risk populations. Further LDL-c reduction may also be achieved with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibition and a recent trial, Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), was the first to show reduction in cardiovascular events for evolocumab. Additional outcome studies of monoclonal antibody and RNA-targeted PCSK9 inhibitors are underway. Quantitative high-density lipoprotein cholesterol (HDL-c) improvements have failed to have clinical impact to date; most recently, cholesteryl ester transfer protein inhibitors and apolipoprotein infusions have demonstrated disappointing results. There are still ongoing trials in both of these areas, but some newer therapies are focusing on HDL functionality and not just the absolute HDL-c levels. There are several ongoing studies in triglyceride reduction including fatty acid therapy, inhibition of apolipoprotein C-3 or ANGTPL3 and peroxisome proliferator-activated receptor-α agonists. Lipid management continues to evolve and these advances have the potential to change clinical practice in the coming years.