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

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. 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.