RNA therapeutics
Review surveys the full Lp(a)-lowering toolkit, from statins and PCSK9 inhibitors to apheresis, CETP inhibitors and RNA-based agents (Life (Basel) 2024)
Original title: Novel Therapeutic Approaches for the Management of Elevated Lipoprotein(a): From Traditional Agents to Future Treatment Options
This review addresses why cardiovascular risk persists in some patients even at therapeutic LDL cholesterol levels, attributing part of this residual risk to elevated Lp(a), which sustains chronic inflammation via oxidized phospholipids on its surface and exerts atherothrombotic effects owing to its roughly 90% structural homology with the fibrinolytic proenzyme plasminogen. The authors survey the full range of therapeutic options for lowering Lp(a) to help personalise treatment and reduce residual cardiovascular risk: agents that increase LDL receptor expression (statins, PCSK9 inhibitors, LDL production inhibitors), and other options including cholesteryl ester transfer protein inhibitors, nicotinic acid derivatives, thyroid hormone mimetics, lipoprotein apheresis, and apolipoprotein(a)-reducing antisense oligonucleotides and small interfering RNAs.
Original abstract
Cardiovascular disease is the leading cause of mortality worldwide. Despite the availability of effective low-density lipoprotein cholesterol (LDL-C) lowering agents, an increased cardiovascular risk is still observed in individuals with therapeutic LDL-C levels. One of these cardiovascular risk factors is elevated plasma lipoprotein(a) (Lp(a)) concentration, which maintains chronic inflammation through the increased presence of oxidized phospholipids on its surface. In addition, due to its 90 percent homology with the fibrinolytic proenzyme plasminogen, Lp(a) exhibits atherothrombotic effects. These may also contribute to the increased cardiovascular risk in individuals with high Lp(a) levels that previous epidemiological studies have shown to exist independently of LDL-C and other lipid parameters. In this review, the authors overview the novel therapeutic options to achieve effective Lp(a) lowering treatment, which may help to define tailored personalized medicine and reduce the residual cardiovascular risk in high-risk patients. Agents that increase LDL receptor expression, including statins, proprotein convertase subtilisin kexin type 9 inhibitors, and LDL production inhibitors, are also discussed. Other treatment options, e.g., cholesterolester transfer protein inhibitors, nicotinic acid derivatives, thyroid hormone mimetics, lipoprotein apheresis, as well as apolipoprotein(a) reducing antisense oligonucleotides and small interfering RNAs, are also evaluated.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.