RNA therapeutics
Systematic review of 29 studies finds statins, fibrates and ezetimibe do little for Lp(a), while apheresis and PCSK9 inhibitors work (Cureus 2024)
Original title: Efficacy of Traditional Anti-lipidemic Drugs in Lowering Lipoprotein(a) Levels: A Systematic Review
This systematic review searched multiple databases and identified 29 research papers examining how various lipid-lowering drugs affect Lp(a) concentration in patients with significantly elevated baseline levels, given that Lp(a) above 30 mg/dL carries higher risk of myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and all-cause mortality. Commonly used agents, statins, fibrates, ezetimibe, and nutraceuticals such as coenzyme Q10, showed no significant effect on Lp(a). In contrast, Lp(a) apheresis and PCSK9 inhibitors effectively reduced plasma Lp(a), and emerging RNA-targeted therapies against apolipoprotein(a), including antisense oligonucleotides and small interfering RNAs, significantly reduced Lp(a) in phase 2 trials. The review concludes that while most traditional lipid-lowering agents have minimal impact on Lp(a), apheresis, PCSK9 inhibitors, and novel RNA-based drugs show real promise, though whether these Lp(a) reductions translate into fewer cardiovascular events remains to be established.
Original abstract
Lipoprotein(a), or Lp(a), was identified in the early 1960. Its role as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) became widely recognized by the late 20th century, regardless of other traditional risk markers such as low-density lipoproteins and high-density lipoproteins. This study aimed to systematically review available literature and compare the efficacy of different lipid-lowering drugs, both approved for clinical use and currently undergoing trials, in lowering Lp(a) levels. A comprehensive search of medical databases including PubMed, PubMed Central (PMC), Medline, ScienceDirect, Cochrane Library, and Google Scholar was conducted to identify relevant studies. A total of 29 research papers met the inclusion criteria, focusing on the impact of various lipid-lowering drugs on Lp(a) concentration in patients with significantly elevated baseline Lp(a) levels. Plasma Lp(a) levels exceeding 30 mg/dL are associated with a higher risk of ASCVD, including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and increased all-cause mortality. Most commonly used lipid-lowering agents, such as statins, fibrates, ezetimibe, and nutraceuticals like coenzyme Q10 (CoQ10), showed no significant effect on Lp(a) plasma levels. However, Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were found to effectively reduce plasma Lp(a) concentrations. Emerging therapies targeting apolipoprotein(a) RNA, including anti-sense oligonucleotides (ASO) and small interfering RNA (siRNA), significantly reduced Lp(a) levels in Phase 2 trials. While several lipid-lowering agents have minimal impact on Lp(a) levels, therapies like Lp(a) apheresis, PCSK-9 inhibitors, and novel RNA-targeting drugs show promise in effectively reducing Lp(a) concentrations. However, whether these reductions translate into decreased cardiovascular events remains to be determined.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.