RNA therapeutics
Antisense and siRNA therapies have reopened the decades-long question of Lp(a)'s causal role, while US, Canadian and European testing guidance still diverges, review finds (Cardiol Rev 2025)
Original title: Lipoprotein(a): A Review of Risk Factors, Measurements, and Novel Treatment Modalities
This review traces the evidence linking Lp(a) to atherosclerotic cardiovascular disease, from large observational studies through genome-wide association and Mendelian randomisation studies, noting that early studies using less sensitive assays initially failed to detect the connection. It highlights that US, Canadian and European organisations still differ in their recommendations for when and how often to test Lp(a), reflecting continued uncertainty about its precise clinical role. The emergence of antisense oligonucleotides and small interfering RNA therapies designed to specifically target Lp(a) mRNA translation has renewed scientific interest, serving the dual purpose of definitively testing the Lp(a)-ASCVD causal link and offering clinicians new management tools. The authors review Lp(a)'s atherogenic mechanisms and survey the pharmacologic therapies currently in development.
Original abstract
The study of lipoprotein(a) [Lp(a)] has long been a source of interest as a possible independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The results of large sample observational studies, genome-wide association studies, and Mendelian randomization studies have been strong indicators supporting the link between ASCVD and Lp(a) despite early studies, with less sensitive assays, failing to show a connection. The recommendations for the indications and frequency of testing Lp(a) levels vary between US, Canadian, and European organizations due to the uncertain role of Lp(a) in ASCVD. The innovation of recent therapies, such as antisense oligonucleotides and small interfering RNA, designed to specifically target and reduce Lp(a) levels by targeting mRNA translation have once more thrust LP(a) into the spotlight of inquiry. These emerging modalities serve the dual purpose of definitively elucidating the connection between elevated Lp(a) levels and atherosclerotic cardiovascular risk, as well as the possibility of providing clinicians with the tools necessary to manage elevated Lp(a) levels in vulnerable populations. This review seeks to examine the mechanisms of atherogenicity of Lp(a) and explore the most current pharmacologic therapies currently in development.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.