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Lp(a): a New Pathway to Target?

Nick S Nurmohamed1,2, Jordan M Kraaijenhof1, Erik S G Stroes3

  • 1Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.

Current Atherosclerosis Reports
|September 6, 2022
PubMed
Summary

Lipoprotein(a) is a key genetic risk factor for cardiovascular disease. New therapies targeting LPA mRNA show promise for significantly lowering Lp(a) levels, offering a new avenue for cardiovascular risk management.

Keywords:
ASCVDAVSLipoprotein(a)

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Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Pharmacology

Background:

  • Genetic and observational studies identify lipoprotein(a) [Lp(a)] as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis.
  • Lp(a) levels are genetically determined, rendering lifestyle interventions ineffective for mitigating Lp(a)-associated risk.

Purpose of the Study:

  • To review the role of Lp(a) as a cardiovascular risk factor.
  • To discuss the limitations of current therapies in lowering Lp(a) and highlight emerging Lp(a)-directed treatments.

Main Methods:

  • Review of genetic and observational evidence linking Lp(a) to cardiovascular disease.
  • Analysis of current lipid-lowering therapies and their impact on Lp(a).
  • Summary of ongoing clinical trials for novel Lp(a)-lowering agents.

Main Results:

  • Traditional lipid-lowering therapies do not significantly reduce Lp(a) levels.
  • Emerging therapies targeting LPA mRNA, including pelacarsen, olpasiran, and SLN360, have demonstrated up to 90% reduction in plasma Lp(a) levels in clinical studies.
  • Phase 3 trials for pelacarsen and olpasiran are underway, with Phase 1 data for SLN360 recently published.

Conclusions:

  • Lipoprotein(a) is a significant, genetically determined risk factor for ASCVD.
  • Novel therapies targeting LPA mRNA are poised to become a crucial new strategy for managing cardiovascular risk by effectively lowering Lp(a).