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

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. 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.

Automated summary

This review critically summarizes the emerging cholesterol-lowering therapy targeting PCSK9, with a focus on the use of anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran. Although both drug classes show similar efficacy in reducing LDL-C levels, the long-term safety and CV outcomes of inclisiran are still unknown.