The Role of Antisense Therapies Targeting Lipoprotein(a)

J Cardiovasc Pharmacol. 2021 Jul 1;78(1):e5-e11. doi: 10.1097/FJC.0000000000001045.

Abstract

Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of preventable death in the United States. Elevated low-density lipoprotein cholesterol (LDL-C) is well known to result in cardiovascular disease. Mainstay therapy for reducing LDL-C and ASCVD risk is statin therapy. Despite achieving desired LDL-C levels with lipid-lowering therapy, cardiovascular residual risk often persists. Elevated lipoprotein(a) [Lp(a)] levels have been highlighted as an inherent independent predictor of ASCVD, and decreasing Lp(a) levels may result in a significant reduction in the residual risk in high-risk patients. To date, there are no approved medications to lower Lp(a) levels. Nicotinic acid, proprotein convertase subtilisin/kexin 9 inhibitors, and antisense oligonucleotide have demonstrated modest to potent Lp(a) reduction. Spotlight has been placed on antisense oligonucleotides and their role in Lp(a) lowering. APO(a)LRx is in the frontline for selectively decreasing Lp(a) concentrations and ongoing research may prove that this medication may lower Lp(a)-mediated residual risk, translating into cardiovascular benefit.

Trial registration: ClinicalTrials.gov NCT04023552.

Publication types

  • Review

MeSH terms

  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / genetics
  • Biomarkers / blood
  • Clinical Trials as Topic
  • Down-Regulation
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / genetics
  • Evidence-Based Medicine
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Lipoprotein(a) / blood*
  • Oligodeoxyribonucleotides, Antisense / adverse effects
  • Oligodeoxyribonucleotides, Antisense / therapeutic use*
  • Oligonucleotides / adverse effects
  • Oligonucleotides / therapeutic use*
  • Treatment Outcome

Substances

  • AKCEA-APO(a)-LRx
  • Biomarkers
  • Hypolipidemic Agents
  • ISIS 304801
  • LPA protein, human
  • Lipoprotein(a)
  • Oligodeoxyribonucleotides, Antisense
  • Oligonucleotides
  • mipomersen

Associated data

  • ClinicalTrials.gov/NCT04023552