RNA therapeutics
Over 20% of the population has Lp(a) above 50 mg/dL, and antisense oligonucleotides can cut it by up to 90% as the Lp(a)HORIZON outcomes trial nears results, a review (Curr Atheroscler Rep 2021)
Original title: Lipoprotein (a): When to Measure and How to Treat?
This review by Rhainds, Brodeur and Tardif surveys evidence for Lp(a) as a causal, independent risk factor across multiple cardiovascular phenotypes, including atherosclerosis, major cardiovascular events, venous thromboembolism and calcific aortic valve disease, contributing to residual risk even with standard LDL-lowering therapy. Elevated Lp(a) (>=50 mg/dL) affects more than 20% of the population, varies by ethnicity due to LPA genetic variants, yet remains underdiagnosed despite its prevalence. Lipoprotein apheresis efficiently lowers Lp(a) and has recently been linked to reduced incident cardiovascular events; statins have neutral or detrimental effects on Lp(a), while PCSK9 inhibitors reduce it by up to 30% and antisense oligonucleotides achieve reductions of up to 90% with good safety. The ongoing Lp(a)HORIZON cardiovascular outcomes trial will provide the first answer on whether selectively lowering Lp(a) with antisense oligonucleotides reduces major cardiovascular events.
Original abstract
Purpose Of Review: The purpose of this article is to review current evidence for lipoprotein (a) (Lp(a)) as a risk factor for multiple cardiovascular (CV) disease phenotypes, provide a rationale for Lp(a) lowering to reduce CV risk, identify therapies that lower Lp(a) levels that are available clinically and under investigation, and discuss future directions.
Recent Findings: Mendelian randomization and epidemiological studies have shown that elevated Lp(a) is an independent and causal risk factor for atherosclerosis and major CV events. Lp(a) is also associated with non-atherosclerotic endpoints such as venous thromboembolism and calcific aortic valve disease. It contributes to residual CV risk in patients receiving standard-of-care LDL-lowering therapy. Plasma Lp(a) levels present a skewed distribution towards higher values and vary widely between individuals and according to ethnic background due to genetic variants in the LPA gene, but remain relatively constant throughout a person's life. Thus, elevated Lp(a) (≥50 mg/dL) is a prevalent condition affecting >20% of the population but is still underdiagnosed. Treatment guidelines have begun to advocate measurement of Lp(a) to identify patients with very high levels that have a family history of premature CVD or elevated Lp(a). Lipoprotein apheresis (LA) efficiently lowers Lp(a) and was recently associated with a reduction of incident CV events. Statins have neutral or detrimental effects on Lp(a), while PCSK9 inhibitors significantly reduce its level by up to 30%. Specific lowering of Lp(a) with antisense oligonucleotides (ASO) shows good safety and strong efficacy with up to 90% reductions. The ongoing CV outcomes study Lp(a)HORIZON will provide a first answer as to whether selective Lp(a) lowering with ASO reduces the risk of major CV events. Given the recently established association between Lp(a) level and CV risk, guidelines now recommend Lp(a) measurement in specific clinical conditions. Accordingly, Lp(a) is a current target for drug development to reduce CV risk in patients with elevated levels, and lowering Lp(a) with ASO represents a promising avenue.
apheresisPCSK9 inhibitionphase 3RNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.