Inclisiran in lipid management: A Literature overview and future perspectives

Biomed Pharmacother. 2021 Nov:143:112227. doi: 10.1016/j.biopha.2021.112227. Epub 2021 Sep 24.

Abstract

Primary and secondary prevention protocols aim at reducing the plasma levels of lipids - with particular reference to low-density lipoprotein cholesterol (LDL-C) plasma concentrations - in order to improve the overall survival and reduce the occurrence of major adverse cardiovascular events. The use of statins has been widely considered as the first-line approach in lipids management as they can dramatically impact on the cardiovascular risk profile of individuals. The introduction of ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors overcame the adverse effects of statins and ameliorate the achievement of the target lipids levels. Indeed, advances in therapies promote the use of specific molecules - i.e. short strands of RNA named small-interfering RNAs (siRNAs) - to suppress the transcription of genes related to lipids metabolism. Recently, the inclisiran has been developed: this is a siRNA able to block the mRNA of the PCSK9 gene. About 50% reduction in low-density lipoprotein cholesterol levels have been observed in randomized controlled trials with inclisiran. The aim of this review was to summarize the literature regarding inclisiran and its possible role in the general management of patients with lipid disorders and/or in primary/secondary prevention protocols.

Keywords: Inclisiran; LDL-C; Lipid management; SiRNAs.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood*
  • Down-Regulation
  • Dyslipidemias / enzymology
  • Dyslipidemias / epidemiology
  • Dyslipidemias / genetics
  • Dyslipidemias / therapy*
  • Heart Disease Risk Factors
  • Humans
  • Primary Prevention
  • Proprotein Convertase 9 / genetics
  • Proprotein Convertase 9 / metabolism*
  • RNA, Small Interfering / adverse effects
  • RNA, Small Interfering / pharmacokinetics
  • RNA, Small Interfering / therapeutic use*
  • RNAi Therapeutics*
  • Risk Assessment
  • Secondary Prevention
  • Treatment Outcome

Substances

  • ALN-PCS
  • Biomarkers
  • Cholesterol, LDL
  • RNA, Small Interfering
  • PCSK9 protein, human
  • Proprotein Convertase 9