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Purpose of review <p>Dyslipidemia remains a dominant modifiable driver of atherosclerotic cardiovascular disease, yet many patients do not reach lipid targets despite contemporary therapies. This review examines small interfering RNA (siRNA) therapeutics as a practical platform for durable lipid lowering with an emphasis on biologic rationale, delivery technologies and emerging clinical evidence.</p> Recent findings <p>Advances in RNA interference biology and siRNA chemical stabilization have enabled targeted hepatic delivery, particularly through N-acetylgalactosamine conjugation. Inclisiran provides proof-of-concept for proprotein convertase subtilisin/kexin type 9 silencing with sustained low-density lipoprotein cholesterol (LDL-C) reductions and infrequent dosing. Beyond LDL-C, investigational siRNA agents targeting apolipoprotein C-III, angiopoietin-like protein 3, and lipoprotein(a) demonstrate marked reductions in triglyceride-rich lipoproteins and genetically driven residual risk pathways.</p> Summary <p>siRNA therapeutics are transitioning from experimental tools to scalable cardiovascular interventions. Their clinical impact will ultimately depend on outcomes-trial evidence, long-term safety, and implementation models that improve adherence while maintaining equitable access.</p>

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Long-Acting RNA Interference Therapies for Cardiovascular Risk Reduction: Current Evidence and Emerging Targets

  • 期刊论文

  • 发表日期：

    2026年3月24日

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  • Kahtan Fadah,
  • Mohammed Alomari,
  • Mohanad Elchouemi,
  • Richard A. Lange

摘要

Purpose of review

Dyslipidemia remains a dominant modifiable driver of atherosclerotic cardiovascular disease, yet many patients do not reach lipid targets despite contemporary therapies. This review examines small interfering RNA (siRNA) therapeutics as a practical platform for durable lipid lowering with an emphasis on biologic rationale, delivery technologies and emerging clinical evidence.

Recent findings

Advances in RNA interference biology and siRNA chemical stabilization have enabled targeted hepatic delivery, particularly through N-acetylgalactosamine conjugation. Inclisiran provides proof-of-concept for proprotein convertase subtilisin/kexin type 9 silencing with sustained low-density lipoprotein cholesterol (LDL-C) reductions and infrequent dosing. Beyond LDL-C, investigational siRNA agents targeting apolipoprotein C-III, angiopoietin-like protein 3, and lipoprotein(a) demonstrate marked reductions in triglyceride-rich lipoproteins and genetically driven residual risk pathways.

Summary

siRNA therapeutics are transitioning from experimental tools to scalable cardiovascular interventions. Their clinical impact will ultimately depend on outcomes-trial evidence, long-term safety, and implementation models that improve adherence while maintaining equitable access.