Emerging drugs for the treatment of hypercholesterolemia

Abstract

Despite the consolidated role of statins and ezetimibe to treat hypercholesterolemia, often the desirable low-density lipoprotein cholesterol (LDL-C) values are not achieved, with a consequent increase of the residual cardiovascular (CV) risk. Areas covered: In this review, we summarize the main pharmacological characteristics of new lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cholesteryl ester transfer protein inhibitors, microsomal triglyceride transfer protein inhibitors, ATP citrate lyase inhibitors, antisense oligonucleotides, small interfering RNA, and peroxisome proliferator-activated receptors type α agonists. The available clinical evidence of efficacy and safety as well as the prospects of application, based on the different mechanisms and targets of action, is critically discussed. Expert opinion: Some of these emerging agents represent an excellent therapeutic strategy to treat patients with LDL largely out of target, resistant or intolerant to statins, trying to minimize the residual CV risk, modulating different classes of lipoproteins, not just LDL. The main challenge for the large use of emerging drugs is their cost. Thus, the correct identification of the adequate target population for treatment is a priority. This is particularly true for safe, powerful, and fully developed drugs such as the PCSK9 inhibitors, for which a relatively large use is potentially expected.

Keywords: Cardiovascular risk; LDL cholesterol; lipoproteins; novel lipid-lowering drugs.