RNA therapeutics
A systematic review of 20 RCTs confirms siRNA therapies significantly lower Lp(a) with mostly mild side effects (Egypt Heart J 2025)
Original title: Small interfering RNA effect on lipoprotein(a): a systematic review
This systematic review searched multiple databases to identify 20 published and ongoing randomised controlled trials examining siRNA therapies, including inclisiran, olpasiran and SLN360, for their effect on Lp(a) levels. Across these trials, siRNA therapy produced significant reductions in Lp(a), with additional reductions in LDL cholesterol and apolipoprotein B, and side effects were typically mild, mainly injection-site reactions. The authors conclude siRNA therapies show clear promise for effectively lowering Lp(a) with a favourable near-term safety profile, while cautioning that further research is needed to establish their long-term safety and efficacy.
Original abstract
Background: This systematic review investigates the effect of small interfering RNA (siRNA) therapies on lipoprotein(a) [Lp(a)] levels. The purpose is to evaluate the outcomes of recent randomized controlled trials (RCTs) involving siRNA treatments aimed at lowering Lp(a) levels, a known cardiovascular risk factor.
Methods: A comprehensive search across multiple databases was conducted, identifying 20 published and ongoing RCTs that examined the effects of siRNA therapies such as inclisiran, olpasiran, and SLN360 on Lp(a) levels. The included studies were analyzed to assess Lp(a) reductions and other lipid-related outcomes.
Results: The RCTs demonstrated significant reductions in Lp(a) levels following siRNA therapy. Additional reductions were noted in LDL-c and apolipoprotein B levels. Side effects were typically mild, including injection site reactions.
Conclusions: siRNA therapies show promise in effectively lowering Lp(a) levels, with minimal adverse effects. However, further research is required to establish their long-term safety and efficacy.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.