Proprotein convertase subtilisin kexin 9 inhibitors: next generation in lipid-lowering therapy

Abstract

Introduction: Statins reduce low-density lipoprotein cholesterol (LDL-C) and are currently the mainstay in the treatment of hyperlipidaemia and subsequently the prevention of atherosclerotic cardiovascular disease (CVD). Nevertheless, there is a need to further lower LDL-C, especially in subjects with severe forms of hypercholesterolaemia despite maximum doses of conventional drugs and/or in those intolerant to existing therapies.

Areas covered: Emerging therapeutic approaches to lowering LDL-C involve blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL-receptor (AMG145, REGN727 and RN316) have been tested in Phase I – III clinical trials for the treatment of hyperlipidaemia in patients at high CVD risk.

Expert opinion: These new agents are administered subcutaneously and have been shown to have major LDL-C and apoB lowering effects either alone or in combination with statins. These novel agents are generally well tolerated and once long-term safety data are available they appear promising therapeutic platforms for the treatment of patients with hypercholesterolaemia at risk for or with CVD not controlled by conventional therapies.

Keywords:

• cardiovascular disease risk
• hypercholesterolaemia
• lipid-lowering treatment
• PCSK9 inhibitors

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organisation 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.

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