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

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.

Keywords: Antisense oligonucleotides; PCSK9 inhibitors; RNA-based therapies; apheresis; cardiovascular disease; children; lipoprotein(a); small interfering RNAs; statin therapy.