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Lipoprotein(a)-lowering therapies: a promising future

Jingwen Zhang1, Ann Marie Navar2, Lale Tokgozoglu3

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

European Heart Journal
|February 13, 2026
PubMed

Insights

Lipoprotein(a) [Lp(a)] significantly increases atherosclerotic cardiovascular disease risk. Emerging therapies show promise for lowering Lp(a) and reducing cardiovascular risk, with Phase III trials ongoing.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Lipoprotein(a) [Lp(a)] is a major genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD).
  • Elevated Lp(a) contributes significantly to residual cardiovascular risk, impacting a substantial population.
  • Current treatments and lifestyle changes minimally affect Lp(a) levels; lipoprotein apheresis is effective but impractical.

Purpose of the Study:

  • To review the limited efficacy of current therapies on Lp(a) levels.
  • To provide an update on novel Lp(a)-targeted therapies in development.
  • To discuss ongoing Phase III trials and potential benefits of Lp(a) reduction.

Main Methods:

  • Review of existing literature on lipid-lowering therapies and Lp(a).
  • Analysis of emerging Lp(a)-targeted therapeutics, including nucleic acid-based approaches and small molecule inhibitors.
  • Examination of data from Phase II trials and ongoing Phase III outcome trials.

Main Results:

  • Emerging Lp(a)-targeted therapies, including antisense oligonucleotides, small interfering RNAs, and a small molecule inhibitor, demonstrated significant Lp(a) reduction in Phase II trials.
  • These novel therapies show potential for substantial and durable Lp(a)-lowering effects.
  • Phase III trials are currently evaluating the impact of these agents on ASCVD outcomes.

Conclusions:

  • Novel Lp(a)-lowering therapies represent a promising advancement in managing cardiovascular risk.
  • Successful outcomes from Phase III trials could transform ASCVD risk reduction strategies for patients with elevated Lp(a).
  • Potential benefits may extend to slowing the progression of calcific aortic valve stenosis.

Keywords:
Antisense oligonucleotideAtherosclerotic cardiovascular diseaseBiomarkersDyslipidaemiaLipoprotein(a)Small interfering RNA

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