RNA therapeutics
Review surveys Lp(a) as a risk-enhancing factor and aortic stenosis driver as ASO and siRNA therapies enter phase 3 (Am J Prev Cardiol 2024)
Original title: Lipoprotein(a): Emerging insights and therapeutics
This review summarises emerging insights into Lp(a), whose strong association with atherosclerotic cardiovascular disease has positioned it as a candidate target for mitigating residual cardiovascular risk. With about 20% of the population carrying Lp(a) above 50 mg/dL and no currently available pharmacological therapy demonstrating substantial Lp(a) reduction, the review covers novel antisense oligonucleotide and small interfering RNA therapies that have shown promising phase 2 results and are now entering phase 3 trials designed to test whether Lp(a) lowering causally reduces ASCVD outcomes. The review also addresses Lp(a)'s role as a risk-enhancing factor, its association with calcific aortic stenosis, the modest effects of existing lipid-lowering therapies on Lp(a), and how levels vary across patient populations, closing with a discussion of the evolving therapeutic landscape.
Original abstract
The strong association between lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease has led to considerations of Lp(a) being a potential target for mitigating residual cardiovascular risk. While approximately 20 % of the population has an Lp(a) level greater than 50 mg/dL, there are no currently available pharmacological lipid-lowering therapies that have demonstrated substantial reduction in Lp(a). Novel therapies to lower Lp(a) include antisense oligonucleotides and small-interfering ribonucleic acid molecules and have shown promising results in phase 2 trials. Phase 3 trials are currently underway and will test the causal relationship between Lp(a) and ASCVD and whether lowering Lp(a) reduces cardiovascular outcomes. In this review, we summarize emerging insights related to Lp(a)'s role as a risk-enhancing factor for ASCVD, association with calcific aortic stenosis, effects of existing therapies on Lp(a) levels, and variations amongst patient populations. The evolving therapeutic landscape of emerging therapeutics is further discussed.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.