Peripheral artery disease patients carry high residual risk from Lp(a), and RNA-targeted therapies could finally address it, Nicholls argues (Curr Opin Lipidol 2025)

Purpose Of Review: To identify the opportunity of targeting patients with elevated lipoprotein(a) [Lp(a)] in patients with peripheral arterial disease (PAD).

Recent Findings: Lp(a) plays a causal role in atherosclerotic cardiovascular disease. Cohort studies demonstrate that elevated Lp(a) levels independently associate with an increased risk of developing PAD. Patients with manifest PAD have a high residual cardiovascular risk, despite use of traditional lipid lowering. The current approach to treatment of patients with high Lp(a) levels involves intensification of management of conventional cardiovascular risk factors and consideration of use of aspirin. In recent years, therapeutic programs have developed injectable RNA targeted agents and a small molecule Lp(a) assembly disrupter that are well tolerated and produce effective Lp(a) lowering. Many of these agents are being evaluated in large cardiovascular outcomes trials. Advances have also looked to develop gene/base editing and epigenetic treatments to lower Lp(a).

Summary: These studies demonstrate that Lp(a) plays an important role in cardiovascular disease, including PAD. However, it remains to be determined if more effective Lp(a) lowering will translate to cardiovascular benefit. If this does prove to be the case, integration of Lp(a) testing and therapeutics has the potential to transform clinical outcomes in people living with PAD.