Pelacarsen and olpasiran achieve up to 90% Lp(a) reductions, positioning routine Lp(a) testing as clinically essential, a review (Curr Opin Lipidol 2023)

Original title: Considerations for routinely testing for high lipoprotein(a)

Curr Opin Lipidol · 18 October 2022 · 7

Nurmohamed NS, Moriarty PM, Stroes ES

This review by Nurmohamed, Moriarty and Stroes argues for routine Lp(a) testing, given that Mendelian randomisation confirms Lp(a) as a likely causal risk factor for atherosclerotic cardiovascular disease and aortic valve disease, linearly related to risk, and largely unaffected by current LDL-C-lowering therapies. RNA-based Lp(a)-lowering therapeutics have positioned Lp(a) as a principal residual risk target: pelacarsen, a liver-specific antisense oligonucleotide in phase 3 trials, has shown Lp(a) reductions of up to 90%, and olpasiran, a small interfering RNA in phase 2 trials, has shown dose-dependent reductions also up to 90%. The authors recommend measuring Lp(a) in every patient at least once, focusing meanwhile on LDL-C and other risk factor reduction in high-Lp(a) patients pending approval of targeted therapies.

Original abstract

Purpose Of Review: Lipoprotein (a) [Lp(a)] is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a). This review focuses on the clinical importance and therapeutic consequences of Lp(a) measurement.

Recent Findings: Development of RNA-based Lp(a) lowering therapeutics has positioned Lp(a) as one of the principal residual risk factors to target in the battle against lipid-driven ASCVD risk. Pelacarsen, which is a liver-specific antisense oligonucleotide, has shown Lp(a) reductions up to 90% and its phase 3 trial is currently underway. Olpasiran is a small interfering RNA targeting LPA messenger RNA, which is being investigated in phase 2 and has already shown dose-dependent Lp(a) reductions up to 90%.

Summary: Lp(a) should be measured in every patient at least once to identify patients with very high Lp(a) levels. These patients could benefit from Lp(a) lowering therapies when approved. In the meantime, therapy in high Lp(a) patients should focus on further reducing LDL-C and other ASCVD risk factors.

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