RNA therapeutics
APO(a)LRx leads the field of antisense oligonucleotides targeting Lp(a)-driven residual cardiovascular risk, a review (J Cardiovasc Pharmacol 2021)
Original title: The Role of Antisense Therapies Targeting Lipoprotein(a)
This review examines antisense oligonucleotide therapies targeting Lp(a), an independent predictor of atherosclerotic cardiovascular disease that persists as residual risk even when LDL cholesterol targets are achieved with statin therapy. With no approved medications currently available to lower Lp(a), the authors survey existing options showing modest to potent reduction, nicotinic acid, PCSK9 inhibitors, and antisense oligonucleotides, with particular focus on APO(a)LRx (pelacarsen), which is at the forefront of selectively lowering Lp(a). The authors suggest that if ongoing research confirms this agent can lower Lp(a)-mediated residual risk, it could translate into meaningful cardiovascular benefit.
Original abstract
Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of preventable death in the United States. Elevated low-density lipoprotein cholesterol (LDL-C) is well known to result in cardiovascular disease. Mainstay therapy for reducing LDL-C and ASCVD risk is statin therapy. Despite achieving desired LDL-C levels with lipid-lowering therapy, cardiovascular residual risk often persists. Elevated lipoprotein(a) [Lp(a)] levels have been highlighted as an inherent independent predictor of ASCVD, and decreasing Lp(a) levels may result in a significant reduction in the residual risk in high-risk patients. To date, there are no approved medications to lower Lp(a) levels. Nicotinic acid, proprotein convertase subtilisin/kexin 9 inhibitors, and antisense oligonucleotide have demonstrated modest to potent Lp(a) reduction. Spotlight has been placed on antisense oligonucleotides and their role in Lp(a) lowering. APO(a)LRx is in the frontline for selectively decreasing Lp(a) concentrations and ongoing research may prove that this medication may lower Lp(a)-mediated residual risk, translating into cardiovascular benefit.
PCSK9 inhibitionpelacarsenRNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.