Small Interfering RNA in Cardiovascular Disease: A New Frontier in Precision Medicine.

Despite advances in traditional lipid-lowering, antithrombotic, and antihypertensive therapies, cardiovascular disease remains the leading cause of mortality worldwide. Small interfering RNA (siRNA) therapeutics harness the endogenous RNA interference pathway to degrade target messenger RNA, thereby reducing synthesis of disease-associated proteins. Because gene silencing occurs intracellularly and persists beyond circulating drug exposure, siRNA agents result in sustained effects with infrequent dosing. Hepatocyte-directed agents targeting PCSK9, LPA, ANGPTL3, APOC3, angiotensinogen, and transthyretin have demonstrated robust and durable reductions in several measures, including atherogenic lipoproteins, blood pressure, and amyloid precursors. Ongoing trials will determine whether these biomarker effects translate into improvements in cardiovascular outcomes. Key challenges include delivery beyond the liver, long-term safety monitoring, off-target mitigation, and economic considerations. Advances in chemical modification, ligand-directed targeting, artificial intelligence-guided sequence design, and reversal strategies are expanding the therapeutic landscape. siRNA-based interventions hold promise as a precision modality capable of reshaping prevention and treatment across the spectrum of cardiovascular disease.