RNA therapeutics
Lp(a) tracks with PAD incidence and limb-threatening ischaemia severity, but whether lowering it helps patients remains untested, review finds (Curr Opin Lipidol 2025)
Original title: Lipoprotein(a) and peripheral artery disease: contemporary evidence and therapeutic advances
This review by Thanigaimani, Kumar and Golledge examines the evidence linking Lp(a) to peripheral artery disease (PAD), a major cause of amputation and reduced quality of life. Human observational studies show strong associations between elevated Lp(a) and increased PAD incidence, greater severity of chronic limb-threatening ischaemia, and more major adverse limb events. Emerging therapies, siRNA, antisense oligonucleotides, PCSK9 inhibitors and lipoprotein apheresis, all demonstrate significant Lp(a)-lowering effects, but the authors emphasise that whether any of these treatments actually benefit PAD patients is still unknown. They call for dedicated trials testing Lp(a)-lowering therapies specifically in PAD populations, alongside research into how the Lp(a)-PAD association varies by sex and ethnicity and the mechanisms linking Lp(a) to limb ischaemia.
Original abstract
Purpose Of Review: Peripheral artery disease (PAD) is a major cause of global health burden, including amputation and impaired quality of life. This review examines the evidence implicating lipoprotein(a) [Lp(a)] in PAD, which is timely as novel therapies lowering Lp(a) are currently being tested in several clinical trials.
Recent Findings: Human observational studies demonstrate strong associations between elevated Lp(a) levels and increased risk of PAD incidence, severity of chronic limb-threatening ischemia, and major adverse limb events. Emerging therapies including small interfering RNA, antisense oligonucleotides, proprotein convertase subtilisin-kexin type 9 inhibitors and lipoprotein apheresis demonstrate significant Lp(a)-lowering effects. However, whether these treatments benefit patients with PAD is currently unknown.
Summary: Lp(a) may be involved in PAD pathogenesis. Lp(a)-lowering therapies may significantly reduce PAD-related events and improve outcomes. Future studies are needed to test Lp(a)-lowering therapies in people with PAD and to explore how the association of Lp(a) varies in different sexes and ethnicities and understand mechanisms by which Lp(a) may contribute to limb ischemia.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.