LIPOPROTEIN(A) AS A THERAPEUTIC TARGET: ARE WE ENTERING A NEW ERA IN CARDIOVASCULAR PREVENTION?


Authors: D. Gospodinov, L. Hadzhiilieva, N. Gerasimov
Keywords: lipoprotein(a), Lp(a), cardiovascular risk, residual risk, antisense therapy, siRNA

Abstract:
Background: Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein associated with increased risk of atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Conventional lipid-lowering therapies have minimal effect on Lp(a), leaving a significant component of residual risk untreated.
Aim: To evaluate the role of Lp(a) as a causal cardiovascular risk factor and assess whether emerging targeted therapies can establish Lp(a) as a therapeutic target.
Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies published between 2015 and 2025 were screened using the terms “lipoprotein(a)”, “Lp(a)”, “cardiovascular risk”, “atherosclerosis”, “PCSK9 inhibitors”, “pelacarsen”, and “olpasiran”. Randomized trials, large observational studies, and guideline documents were prioritized. The final analysis included 20 key sources.
Results: Elevated Lp(a) is independently associated with increased cardiovascular risk. Statins do not reduce Lp(a), while PCSK9 inhibitors achieve modest reductions. Novel therapies based on antisense oligonucleotides and small interfering RNA demonstrate substantial Lp(a) lowering in phase 2 studies.
Conclusion: Lp(a) is shifting from a risk marker to a potential therapeutic target. Ongoing outcome trials will determine its role in cardiovascular prevention.Download article