Investigational therapies for hypercholesterolemia

ABSTRACT

Introduction: Cardiovascular morbidity and mortality are of increasing concern, not only to patients but also to the health care profession and service providers. The preventative benefit of treatment of dyslipidaemia is unquestioned but there is a large, so far unmet need to improve clinical outcome. There are exciting new discoveries of targets that may translate into improved clinical outcome.

Areas covered: This review highlights some new pathways in cholesterol and triglyceride metabolism and examines new targets, new drugs and new molecules. The review includes the results of recent trials of relatively new drugs that have shown benefit in cardiovascular endpoint outcomes, drugs that have been licenced without endpoint trials yet available and new drugs that have not yet been licenced but have produced exciting results in animal studies and some in early phase 2 human studies.

Expert opinion: The new areas that have been discovered as the cause of dyslipidaemia have opened up a host of new targets for new drugs including antisense RNA’s, microRNA’s and human monoclonal antibodies. The plethora of new targets and new drugs has made it an extraordinarily exciting time in the development of therapeutics to combat atherosclerosis.

KEYWORDS:

• Apolipoprotein A1
• Apolipoprotein Clll
• cholesteryl ester transfer protein (CETP)
• diabetes
• dyslipidaemia
• lipoprotein (a)
• low density lipoprotein LDL
• LDL receptor: microsomal triglyceride transfer protein (MTP)
• Niemann Pick C1-like1 (NPC1-L1)
• ) PCSK9: low density lipoprotein
• Triglyceride

Article highlights

• Although statins reduce major cardiovascular events, an unmet need still exists to improve cardiovascular outcome.

• New treatments have been developed through major advances in our understanding of cholesterol metabolism.

• Excitement in PCSK9 inhibitors is growing but long term prevention studies still awaited.

• The importance of triglyceride rich proteins and new understanding in their regulation has led to the development of interesting new drugs.

• The importance of Lp(a) has resurfaced and the potential to reduce it is an exciting new development.

• HDL remains an inigma with ongoing discussion of quantity vs quality.

This box summarizes key points contained in the article.

Declaration of interest

G. Tomkin and D. Owens have received grants or speaker honorariums from MSD, Lilly, Novo Nordisk, Takeda, Merck, Bristol Myers Squib, Bayer, Lypha. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper was not funded.