Pharmacokinetics, pharmacodynamics and clinical efficacy of non-statin treatments for hypercholesterolemia

ABSTRACT

Introduction: Hypercholesterolemia is the main modifiable risk factor for atherosclerosis progression and cardiovascular disease (CVD) development. Its pharmacological management is usually based on the prescription of statins, that in some cases are not however fully effective to reach the desired Low-Density-Lipoproteins cholesterol (LDL-C) target, or are not tolerated by patients due to side effects.

Areas covered: This manuscript summarizes the basic properties of the emerging new classes of lipid-lowering drugs such as ezetimibe, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, and Microsomal Triglyceride Transfer Protein (MTP) inhibitors, also citing new drugs in development. Our aim is to describe the main pharmacodynamic and pharmacokinetic characteristics, the available efficacy, tolerability and safety data obtained in randomized clinical trials where these drugs were tested.

Expert opinion: Non-statin lipid-lowering drugs can be considered an excellent strategy to reduce the residual CV risk, also represented by non-target LDL-C values and high lipoprotein(a) serum levels. In particular, the approved PCSK9 inhibitors (Evolocumab and Alirocumab) have been very effective in optimizing plasma LDL-C values and reducing CV event risk.

KEYWORDS:

• LDL-cholesterol
• cardiovascular risk
• LDL-cholesterol-lowering
• ezetimibe
• Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors
• Cholesteryl Ester Transfer Protein (CETP) inhibitor
• Microsomal triglyceride Transfer Protein (MTP) inhibitor

Article highlights

• Despite the efficacy and safety of statins, they are not always sufficient to reach the desired LDL-C target, because they are not powerful enough or not tolerated

• New drugs have been developed to support statin efficacy or to replace them when not tolerated

• Reduction of cardiovascular risk has been observed with the use of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors

• The long-term efficacy of Microsomal Triglyceride Transfer Protein (MTP) inhibitors and other new lipid-lowering drugs has been yet to be defined.

• More trials are needed to verify the efficacy and safety of PCKS inhibitors and MTP inhibitors in patients with chronic kidney failure and/or liver diseases

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this paper have nothing to disclose.

Additional information

Funding

This paper was not funded.