RNA therapeutics
Review by Nicholls and Nelson asks which patients stand to benefit most as Lp(a)-lowering agents near approval (Kardiol Pol 2025)
Original title: Current perspectives on Lp(a)-lowering therapies: Who may benefit?
This review examines the current and emerging clinical role of Lp(a) as evidence implicating it in atherosclerosis and calcific aortic valve disease has grown, while noting that no therapy selectively lowering Lp(a) is yet available in clinical practice. In the interim, an elevated Lp(a) mainly functions as a risk-enhancer that should prompt more intensive management of established cardiovascular risk factors. The authors summarise agents in clinical development, antisense oligonucleotides and small interfering RNAs that inhibit hepatic apolipoprotein(a) synthesis, and oral small molecules that block apolipoprotein(a)-apolipoprotein B binding, noting early studies show reductions of more than 80% in Lp(a) with good tolerability. Several of these agents are now in large outcome trials to establish their effect on cardiovascular events, and the review discusses how the field's evolution will shape which patients ultimately benefit from Lp(a)-targeted prevention.
Original abstract
Increasing evidence has implicated lipoprotein(a) [Lp(a)] in the pathogenesis of atherosclerosis and calcific aortic valve disease. There are currently no therapies available in clinical practice that selectively lower Lp(a) levels. In the current state, the presence of an elevated Lp(a) level plays an important role in risk enhancement and triaging patients to the use of more intensive targeting of established cardiovascular risk factors. A number of therapies are currently in clinical development with the potential to reduce formation of Lp(a) particles. This includes antisense oligonucleotides and short interfering RNA agents that inhibit hepatic apolipoprotein(a) synthesis and oral small molecule inhibitors that inhibit binding of apolipoprotein(a) and apolipoprotein B. Early clinical studies have demonstrated the ability of these agents to effectively reduce Lp(a) levels by more than 80%, and they are well tolerated by patients. A number of these agents are currently being evaluated in large clinical trials to determine their impact on cardiovascular events. The evolution of this field and implications for the clinical approach to the prevention of cardiovascular disease will be reviewed.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.