REVIEW article
Front. Med.
Sec. Precision Medicine
This article is part of the Research TopicPrecision Medicine in Cardiovascular Remodeling: Bridging Pathogenesis to Personalized Therapeutic StrategiesView all 6 articles
Emerging Therapies Targeting Lipoprotein(a): The Next Frontier in Cardiovascular Risk Reduction
Provisionally accepted
- Qassim University College of Pharmacy, Buraydah, Saudi Arabia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle composed of apolipoprotein B-100 covalently linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The Lp(a) particle is enriched with oxidized phospholipids (OxPLs), which confer enhanced atherogenic and pro-inflammatory properties compared with low-density lipoprotein (LDL). Robust genetic and epidemiologic evidence demonstrates that elevated Lp(a) levels are independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. However, no pharmacologic therapy has yet been approved to specifically lower Lp(a) or to demonstrate a reduction in cardiovascular events. Antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, zerlasiran), and oral small-molecule Lp(a) inhibitors (e.g., muvalaplin) have demonstrated profound reductions in circulating Lp(a) concentrations, typically achieving decreases of 80-90%. In some studies, the reductions approached or achieved near-complete suppression of apo(a) synthesis. Current genetic and modeling evidence suggests that an absolute reduction of at least 50 mg/dL in Lp(a) levels is required to achieve meaningful cardiovascular benefit. Large-scale outcome trials are now underway to assess the effects of these emerging therapies on cardiovascular and valvular outcomes. Early findings indicate favorable effects on oxidized phospholipids and vascular inflammation, suggesting broader anti-atherogenic potential. As these agents progress toward clinical use, routine Lp(a) measurement and risk stratification will become increasingly essential for personalized cardiovascular prevention. This review summarizes the molecular biology of Lp(a), highlights limitations of current therapies, and discusses emerging RNA-based and small-molecule approaches with the potential to redefine the management of residual cardiovascular risk.
Keywords: Antisense oligonucleotide (ASO), atheroclerotic cardiovascular disease, cardiovascular risk, Lipoprotein(a), small interfering RNA
Received: 18 Oct 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Alhomoud. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ibrahim S. Alhomoud
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.