Promising new therapies for the treatment of hypercholesterolemia

ABSTRACT

Introduction: Statins are currently the most commonly used agents for treatment of hypercholesterolemia in patients with atherosclerotic cardiovascular disease. However, some patients on statins do not achieve their treatment goals or are intolerant to statins. Therefore, new therapies for treatment of hypercholesterolemia are under investigation.

Areas covered: This article reviews the new emerging medications for the treatment of hypercholesterolemia and discusses their efficacy and safety profile based on literature searches that included human studies published on PubMed and reported clinical trials.

Expert opinion: Inhibition of the PCSK9 protein by monoclonal antibodies results in a dramatic 40%-60% lowering of serum low-density lipoprotein cholesterol (LDL-C). This is in addition to LDL-C lowering achieved by statins. Multiple clinical studies have demonstrated the high selectivity of these antibodies for the PCSK9 pathway and their long-term safety and efficacy. Alirocumab and evolocumab have been approved by the FDA for the treatment of patients with heterozygous familial hypercholesterolemia and patients with clinical atherosclerotic cardiovascular disease) who do not achieve their LDL-C target on maximal tolerated statin treatment and dietary modification. In addition, evolocumab has been approved by the FDA for homozygous familial hypercholesterolemia. However, the long-term efficacy and safety of PCSK9 inhibitors are unknown.

KEY WORDS:

• Alirocumab
• anacetrapib
• apo A1
• apo B100
• bococizumab
• CETP
• cholesterylester transfer protein
• dalcetrapib
• evacetrapib
• evolocumab
• HDL-C
• high density lipoprotein
• hypercholesterolemia
• hyperlipidemia
• LDL-C
• lomintapide
• low density lipoprotein
• microsomal triglyceride transfer protein
• mipomerson
• monoclonal antibodies
• MTP
• PCSK9
• proprotein converase subtilisin/kexin type 9
• VLDL
• very low density lipoprotein
• torcetrapib

Article highlights

• Statins are the mainstay of therapy for hypercholesterolemia, especially for the treatment and prevention of CAD.

• Despite advances in therapy, a substantial number of patients will experience adverse effects from statins or will be unable to achieve optimum LDL-C levels despite maximal therapy.

• PCSK9 inhibitors have recently been approved as an adjunct to maximally tolerated statin therapy in patients with primary hyperlipidemia or hoFH.

• Agents targeting the CETP, MTP, RNA, and other pathways of cholesterol synthesis are being developed but have met with little success or are not ready for approval.

• The long-term safety of PCSK9 antibodies has been demonstrated for up to 2 years.

• Gaps in PCSK9 trials refer to populations not studied; children with FH, human immunodeficiency virus dyslipidemia, aboriginal populations, and diabetics with dyslipidemia.

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.