Should children with high Lp(a) be treated with ASOs or siRNAs? A Dutch review argues yes, but only for those at highest cardiovascular risk (Expert Opin Pharmacother 2022)

Original title: Pharmacotherapy for children with elevated levels of lipoprotein(a): future directions

Expert Opin Pharmacother · 12 September 2022 · 5

de Boer LM, Wiegman A, Swerdlow DI, Kastelein JJP, Hutten BA

This review by de Boer, Wiegman, Swerdlow, Kastelein and Hutten examines future pharmacotherapy directions for children with elevated Lp(a), a largely genetically fixed risk factor present from early childhood. The authors survey pharmacological treatments in clinical development, with particular focus on antisense oligonucleotides and small interfering RNAs targeting LPA, which have shown highly effective Lp(a) lowering in adults. Given the urgent need for well-designed prospective studies assessing the impact of elevated Lp(a) specifically in childhood, the authors argue that if the Lp(a) hypothesis is confirmed in both adults and children, treatment should initially be limited to children at the highest cardiovascular risk, including those with familial hypercholesterolaemia and potentially paediatric stroke.

Original abstract

Introduction: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). With the advent of the antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) targeted at LPA, that are highly effective for lowering Lp(a) levels, this risk factor might be managed in the near future. Given that Lp(a) levels are mostly genetically determined and once elevated, present from early age, we have evaluated future directions for the treatment of children with high Lp(a) levels.

Areas Covered: In the current review, we discuss different pharmacological treatments in clinical development and provide an in-depth overview of the effects of ASOs and siRNAs targeted at LPA.

Expert Opinion: Since high Lp(a) is an important risk factor for ASCVD and given the promising effects of both ASOs and siRNAs targeted at apo(a), there is an urgent need for well-designed prospective studies to assess the impact of elevated Lp(a) in childhood. If the Lp(a)-hypothesis is confirmed in adults, and also in children, the rationale might arise for treating children with high Lp(a) levels. However, we feel that this should be limited to children with the highest cardiovascular risk including familial hypercholesterolemia and potentially pediatric stroke.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.