RNA therapeutics
From niacin's 20% cut to apo(a)-targeted drugs' 80% reduction, a mini review maps the full spectrum of Lp(a)-lowering options (J Clin Med Res 2025)
Original title: Lipoprotein(a)-Lowering Drugs: A Mini Review
This mini review by Hamasaki and Kotani summarises available and emerging approaches to lowering Lp(a), a challenge historically complicated by the particle's unique structure and metabolic pathway. Among non-targeted lipid-lowering drugs, statins have variable effects on Lp(a), while niacin and PCSK9 inhibitors each reduce Lp(a) by over 20%; estrogen-related drugs and certain supplements can also lower Lp(a), offering further insight into its regulation. The authors describe apo(a)-targeted antisense oligonucleotides, small interfering RNAs, and a small-molecule Lp(a)-formation inhibitor as the most promising recent development, specifically reducing Lp(a) by approximately 80%. They note that treatment strategies for Lp(a) are poised to be updated once clinical trial evidence on cardiovascular event reduction and an effective Lp(a) treatment threshold become available.
Original abstract
Lipoprotein(a) (Lp(a)) is a type of lipoprotein consisting of low-density lipoprotein with apoprotein(a) (apo(a)) and is a risk factor for cardiovascular disease (CVD). Lowering Lp(a) levels may improve CVD outcomes, but this has been challenging owing to the unique structure and metabolic pathway of Lp(a). Recently, several new treatments using apo(a)-targeting drugs have been developed to reduce Lp(a) levels. Here, we briefly summarize the treatments, including earlier attempts at reducing Lp(a). Some lipid-lowering drugs can reduce Lp(a) levels in a non-targeted manner; while the effect of statins varies, niacin and proprotein convertase subtilisin/kexin type 9 inhibitors exhibit a reduction of over 20% in Lp(a) levels. Estrogen-related drugs and certain supplements can reduce Lp(a) levels, which may promote a deeper understanding of the modulation of Lp(a) levels. An apo(a) antisense oligonucleotide, small interfering RNAs, and a small molecule Lp(a)-formation inhibitor have recently been developed as promising drugs that specifically reduce Lp(a) levels by approximately 80%. The treatment strategies for Lp(a) are set to be updated, although we are awaiting clinical evidence on the reduction of CVD events by new treatments and the effective threshold for Lp(a) levels for the prevention of CVD.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.