Efficacy and safety of PCSK9 monoclonal antibodies

ABSTRACT

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that have been developed since the discovery of the PCSK9 protein in 2003. In addition to background statin treatment, they reduce low-density lipoprotein cholesterol (LDL-C) to unprecedented levels and have shown encouraging results in improving cardiovascular events. Concerns regarding the safety of PCSK9 inhibitors and very low LDL-C have somewhat been allayed after several longer-term prospective studies.

Areas covered: A comprehensive literature search was carried out including article searches in electronic databases (EMBASE, PUBMED, OVID) and reference lists of relevant articles. This review examines novel research concerning PCSK9 monoclonal antibodies and cardiovascular outcomes with a special focus on their safety and tolerability. The safety of very low LDL-C concentrations and the link between LDL-C lowering and diabetes is also discussed.

Expert opinion: PCSK9 monoclonal antibodies when added to background statin therapy, lowers LDL-C to previously unattainable levels. This is safe with little undesirable effects and impacts positively on cardiovascular disease. Current guidance limits their use to primary prevention. Cost effectiveness should be taken into consideration before allowing a wider use of this new class of cholesterol lowering therapy and more data on their long-term safety is welcome.

KEYWORDS:

• PCSK9
• statin
• cardiovascular disease
• proprotein convertase subtilisin/kexin type 9
• familial hypercholesterolemia
• evolocumab
• bococizumab
• alirocumab
• low LDL cholesterol
• LDL and diabetes

Article highlights

• PCSK9 monoclonal antibodies reduce LDL-C to previously unprecedented levels and improve cardiovascular outcomes.

• LDL-C as low as 25mg/dl is shown to be safe.

• LDL-C lower than 25mg/dl is probably safe but more data are needed.

• More data on the effect of PCSK9 inhibitors on risk of type 2 diabetes are required.

• PCSK9 inhibitors do not appear to cause neurocognitive adverse effects.

• These drugs are usually well-tolerated, However, more data on safety of long-term use are needed.

This box summarizes key points contained in the article.

Acknowledgment

We acknowledge support from the Manchester Comprehensive Local Research Network, the National Institute for Health Research/Wellcome Trust Clinical Research Facility in Manchester and lipid disease fund.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.