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Updated: May 12, 2025

Isolation of High-density Lipoproteins for Non-coding Small RNA Quantification
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Small interfering RNA effect on lipoprotein(a): a systematic review

Omar Almaadawy1, Mohamed Mar'ey Hesn2, Yomna Ayman Elsalamony3

  • 1Internal Medicine Department, MedStar Health, 201 E. University Pkwy, Baltimore, MD, 21218, USA. omar.a.almaadawy@medstar.net.

The Egyptian Heart Journal : (EHJ) : Official Bulletin of the Egyptian Society of Cardiology
|May 8, 2025
PubMed
Abstract

Insights

Small interfering RNA (siRNA) therapies effectively lower lipoprotein(a) [Lp(a)] levels, a key cardiovascular risk factor. These treatments show promise with mild side effects, warranting further investigation into long-term outcomes.

Area of Science:

  • Cardiovascular medicine
  • Pharmacology
  • Molecular biology

Background:

  • Lipoprotein(a) [Lp(a)] is a significant independent risk factor for cardiovascular disease.
  • Current therapeutic options for lowering Lp(a) are limited.
  • Small interfering RNA (siRNA) represents a novel therapeutic strategy targeting Lp(a) reduction.

Purpose of the Study:

  • To systematically review the efficacy of siRNA therapies in reducing lipoprotein(a) [Lp(a)] levels.
  • To evaluate outcomes from recent randomized controlled trials (RCTs) of siRNA treatments for Lp(a) lowering.
  • To assess the safety and tolerability profile of these emerging therapies.

Main Methods:

  • A comprehensive literature search was performed across major scientific databases.
  • Included 20 published and ongoing randomized controlled trials (RCTs).
  • Analyzed studies evaluating siRNA therapies like inclisiran, olpasiran, and SLN360 for their impact on Lp(a), LDL-c, and apolipoprotein B levels.

Main Results:

  • siRNA therapies demonstrated statistically significant reductions in circulating Lp(a) levels.
  • Concomitant reductions in low-density lipoprotein cholesterol (LDL-c) and apolipoprotein B were observed.
  • Adverse events were generally mild, with injection site reactions being the most commonly reported side effect.

Conclusions:

  • siRNA therapies are a promising new class of drugs for effectively lowering Lp(a) levels.
  • These therapies exhibit a favorable safety profile with minimal adverse effects.
  • Further long-term studies are necessary to fully establish the safety and efficacy of siRNA for cardiovascular risk reduction.
Keywords:
Apolipoprotein BCardiovascular riskCoronary artery diseaseHyperlipidemiaInclisiranLDL-cLipid-lowering therapyLipoprotein(a)Lp(a)OlpasiranRandomized controlled trialsSLN360siRNA

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