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Review
. 2025 May 8;77(1):44.
doi: 10.1186/s43044-025-00635-1.

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

Omar Almaadawy #  1 , Mohamed Mar'ey Hesn #  2 , Yomna Ayman Elsalamony  3 , Omar Ayman Abobakr  2 , Abdelrahman Hossam Elshimy  4 , Khaled Alsayed Abulkhair  5 , Mahmoud Mohamed Negm  5 , Ahmed Yasser Shaban  6 , Yakubu Bene-Alhasan  7 , Frank Annie  8 , Adam Belcher  8 , Ahmed Ramy Elashery  8
Affiliations
Review

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

Omar Almaadawy et al. Egypt Heart J. .

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.

Keywords: Apolipoprotein B; Cardiovascular risk; Coronary artery disease; Hyperlipidemia; Inclisiran; LDL-c; Lipid-lowering therapy; Lipoprotein(a); Lp(a); Olpasiran; Randomized controlled trials; SLN360; siRNA.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Small interfering RNA (siRNA) mechanis of action
Fig. 2
Fig. 2
PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only. Red color * indicates, ongoing studies identified manually (n = 11). Black color * consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). Black color ** indicates, if automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools
Fig. 3
Fig. 3
Baseline characteristics (age, BMI, gender and race) across studies
Fig. 4
Fig. 4
Mean Lp(a) reduction across studies
See this image and copyright information in PMC

References

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