Low-density lipoprotein cholesterol lowering therapies: what is on the horizon?

Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with an increased risk for cardiovascular disease (CVD). Statins have been the cornerstone of lipid therapy to lower LDL-C for the past two decades, but despite significant clinical efficacy in a majority of patients, a large residual risk remains for the development of initial or recurrent atherosclerotic CVD. In addition, owing to the side-effects, a significant percentage of patients cannot tolerate any statin dose or a high enough statin dose. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight these novel therapeutic agents including antisense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and microsomal triglyceride transfer protein inhibitors. For each therapeutic class, an overview of mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be discussed.