# Small interfering RNA effect on lipoprotein(a): a systematic review

## TL;DR

This review examines how siRNA therapies like inclisiran and olpasiran effectively lower Lp(a) and LDL-C, key risk factors for heart disease, with minimal side effects.

## Contribution

The study provides a systematic comparison of siRNA therapies for Lp(a) and LDL-C reduction, highlighting their efficacy and safety profiles.

## Key findings

- siRNA therapies significantly reduce Lp(a) and LDL-C levels in RCTs.
- Olpasiran is more effective at lowering Lp(a), while inclisiran is better for LDL-C reduction.
- siRNA treatments show favorable safety profiles with mild side effects like injection site pain.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s43044-025-00635-1.

The review evaluates the efficacy of SiRNA therapies, including inclisiran, SLN360, and olpasiran, in effectively lowering Lp(a) and LDL-C levels, which are critical in reducing the risk of cardiovascular diseases.Olpasiran is more effective in lowering Lp(a) more than inclisiran and SLN360, while inclisiran is more effective in lowering LDL-C more than olpasiran and SLN360.It assesses the safety profiles of these SiRNA drugs, finding them generally favorable across the studies analyzed, with injection site pain being the most reported side effect. Long-term safety profiles yet to be determined.The analysis spans various SiRNA medications, providing a comparative insight into their performance, dose-responsiveness, and the potential for personalized treatment approaches in lipid management.The call for further research is emphasized, particularly the need for more extensive and rigorous randomized controlled trials. These future studies are crucial for validating the long-term benefits, safety, and efficacy of SiRNA therapies in a diverse patient demographic.Additionally, there is advocacy for studies focusing specifically on the reduction of cardiac risk factors. Understanding SiRNA therapies' impact on cardiovascular risk factors beyond Lp(a) and LDL-C could revolutionize preventive strategies in cardiovascular health.

The review evaluates the efficacy of SiRNA therapies, including inclisiran, SLN360, and olpasiran, in effectively lowering Lp(a) and LDL-C levels, which are critical in reducing the risk of cardiovascular diseases.

Olpasiran is more effective in lowering Lp(a) more than inclisiran and SLN360, while inclisiran is more effective in lowering LDL-C more than olpasiran and SLN360.

It assesses the safety profiles of these SiRNA drugs, finding them generally favorable across the studies analyzed, with injection site pain being the most reported side effect. Long-term safety profiles yet to be determined.

The analysis spans various SiRNA medications, providing a comparative insight into their performance, dose-responsiveness, and the potential for personalized treatment approaches in lipid management.

The call for further research is emphasized, particularly the need for more extensive and rigorous randomized controlled trials. These future studies are crucial for validating the long-term benefits, safety, and efficacy of SiRNA therapies in a diverse patient demographic.

Additionally, there is advocacy for studies focusing specifically on the reduction of cardiac risk factors. Understanding SiRNA therapies' impact on cardiovascular risk factors beyond Lp(a) and LDL-C could revolutionize preventive strategies in cardiovascular health.

The online version contains supplementary material available at 10.1186/s43044-025-00635-1.