PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection

Abstract

Purpose of Review: Treatment of dyslipidemia represents one of the most crucial strategies to reduce risk of atherosclerotic cardiovascular (CV) disease (ASCVD). In this review, we critically summarize our knowledge on emerging cholesterol-lowering therapy, targeting PCSK9, paying particular attention on treatment allocation of two drug groups, currently available for clinical use, namely, anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran, a first-in-class small interfering RNA against PCSK9. Recent Findings: Although both drug classes show a pronounced, but fairly similar reduction in LDL-cholesterol, their long-term safety is still unknown. Compared to mAbs, inclisiran has a more favorable dosing regimen with biannual application that might improve therapeutic adherence significantly. However, a CV outcome trial (CVOT) for inclisiran is still missing. Summary: If inclisiran will be safe and effective in ongoing/future CVOTs, it has a huge potential to overcome medication non-compliance, thereby providing a powerful therapeutic option to decrease the burden of ASCVD.