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

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.