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

Curr Cardiol Rep. 2022 Nov;24(11):1657-1667. doi: 10.1007/s11886-022-01782-6. Epub 2022 Sep 10.

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. 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.

Keywords: Alirocumab; Dyslipidemia; Evolocumab; Inclisiran; PCSK9 mAb; Small interfering RNA.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal* / therapeutic use
  • Cholesterol*
  • Humans
  • Patient Selection
  • Proprotein Convertase 9
  • RNA, Small Interfering / therapeutic use

Substances

  • Antibodies, Monoclonal
  • RNA, Small Interfering
  • Cholesterol
  • PCSK9 protein, human
  • Proprotein Convertase 9