20-25% of people worldwide have Lp(a) 50 mg/dL or above, and existing drugs barely touch it while three new agents in development could change that, a review (Pharmacotherapy 2023)

Original title: Role of lipoprotein(a) in atherosclerotic cardiovascular disease: A review of current and emerging therapies

Pharmacotherapy · 26 July 2023 · 6

Alhomoud IS, Talasaz A, Mehta A, Kelly MS, Sisson EM, Bucheit JD, Brown R, Dixon DL

This review summarises current and emerging approaches to elevated Lp(a), estimating that 20% to 25% of the global population has Lp(a) >=50 mg/dL (>=125 nmol/L). Diet and lifestyle have little to no effect on Lp(a), and lipoprotein apheresis, the only approved treatment, is time-intensive and only modestly effective. Statins modestly raise Lp(a) and have not been shown to alter Lp(a)-mediated cardiovascular risk, while alirocumab, evolocumab and inclisiran reduce Lp(a) by 20-25%, though the clinical benefit of this reduction remains uncertain; niacin also lowers Lp(a) but its risk-reducing effect and side-effect profile limit its use. Three investigational compounds, the siRNAs olpasiran and SLN360 and the antisense oligonucleotide pelacarsen, block hepatic apo(a) synthesis and are in various stages of clinical development. Screening and management recommendations for elevated Lp(a) currently vary widely across guidelines.

Original abstract

Lipoprotein(a), or Lp(a), is structurally like low-density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)]. Due to its prothrombotic and proinflammatory properties, Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are genetically determined, and it is estimated that 20%-25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L). Diet and lifestyle interventions have little to no effect on Lp(a) levels. Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but is time-intensive for the patient and only modestly effective. Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest; however, currently available lipid-lowering therapies have limited effectiveness in reducing Lp(a) levels. Although statins are first-line agents to reduce LDL cholesterol levels, they modestly increase Lp(a) levels and have not been shown to change Lp(a)-mediated ASCVD risk. Alirocumab, evolocumab, and inclisiran reduce Lp(a) levels by 20-25%, yet the clinical implications of this reduction for Lp(a)-mediated ASCVD risk are uncertain. Niacin also lowers Lp(a) levels; however, its effectiveness in mitigating Lp(a)-mediated ASCVD risk remains unclear, and its side effects have limited its utilization. Recommendations for when to screen and how to manage individuals with elevated Lp(a) vary widely between national and international guidelines and scientific statements. Three investigational compounds targeting Lp(a), including small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen), are in various stages of development. These compounds block the translation of messenger RNA (mRNA) into apo(a), a key structural component of Lp(a), thereby substantially reducing Lp(a) synthesis in the liver. The purpose of this review is to describe current recommendations for screening and managing elevated Lp(a), describe the effects of currently available lipid-lowering therapies on Lp(a) levels, and provide insight into emerging therapies targeting Lp(a).

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.