Lp(a): a New Pathway to Target?

Curr Atheroscler Rep. 2022 Nov;24(11):831-838. doi: 10.1007/s11883-022-01060-4. Epub 2022 Sep 6.

Abstract

Purpose of review: Over the past decades, genetic and observational evidence has positioned lipoprotein(a) as novel important and independent risk factor for cardiovascular disease (ASCVD) and aortic valve stenosis.

Recent findings: As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect. There are multiple Lp(a)-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90%: pelacarsen, olpasiran, and SLN360. Pelacarsen is currently investigated in a phase 3 cardiovascular outcome trial expected to finish in 2024, while olpasiran is about to proceed to phase 3 and SLN360's phase 1 outcomes were recently published. If proven efficacious, Lp(a) will soon become the next pathway to target in ASCVD risk management.

Keywords: ASCVD; AVS; Lipoprotein(a).

Publication types

  • Review

MeSH terms

  • Aortic Valve Stenosis*
  • Cardiovascular Diseases* / drug therapy
  • Cholesterol, LDL
  • Humans
  • Lipoprotein(a) / genetics
  • Oligonucleotides, Antisense / therapeutic use
  • RNA, Messenger
  • Risk Factors

Substances

  • Cholesterol, LDL
  • Lipoprotein(a)
  • Oligonucleotides, Antisense
  • RNA, Messenger