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Emerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction
Ibrahim S. Alhomoud. Frontiers in Medicine, 2025-12-18
Topic: Brain proteins, microglia and lab models
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 that specifically lower Lp(a) or to demonstrate a reduction in cardiovascular events. Antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, and 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 a near-complete suppression. 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 benefits. 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 the limitations of current therapies, and discusses emerging RNA-based and small-molecule approaches with the potential to redefine the management of residual cardiovascular risk.
Key findings
- 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.
- Antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, and 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%.
- 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 benefits.
Why it matters
This review is about lipoprotein(a) and cardiovascular risk, not Alzheimer's disease, so it provides no information on Alzheimer's treatment, cure or prevention. It describes experimental therapies that lower lipoprotein(a) and notes that large outcome trials are still underway.
New to this subject? Start with our plain-English guide: Prevention →
Study details
- Evidence strengthLow
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Medicine) |
| Journal's citation record | 1 / 4 | Frontiers in Medicine: journal h-index 149 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Ibrahim S. Alhomoud: h-index 8 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Qassim University: institution h-index 207 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41488100) |
| Free to read | 2 / 2 | Free to read |
| Total | 35 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fmed.2025.1727918
- PubMed: 41488100
- Original source →
- Free full text: Frontiers in Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Alhomoud, I. S. (2025). Emerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction. Frontiers in Medicine. https://doi.org/10.3389/fmed.2025.1727918
Vancouver
Alhomoud IS. Emerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction. Frontiers in Medicine. 2025. doi:10.3389/fmed.2025.1727918. PMID: 41488100.
BibTeX
@article{alhomoud2025-41488100,
author = {Alhomoud, Ibrahim S.},
title = {{Emerging therapies targeting lipoprotein(a): the next frontier in cardiovascular risk reduction}},
journal = {Frontiers in Medicine},
year = {2025},
doi = {10.3389/fmed.2025.1727918},
pmid = {41488100},
url = {https://doi.org/10.3389/fmed.2025.1727918}
}
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