Advances in RNA based therapeutics for atherosclerosis: From bench to bedside

Despite advances in statin therapy and other lipid-lowering agents, atherosclerosis continues to drive a substantial global burden of cardiovascular disease (CVD). RNA-based therapeutics, including small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), are emerging as innovative tools with the potential to complement or even redefine current treatment strategies. This review aims to provide clinicians with an up-to-date overview of RNA-based therapies targeting atherosclerotic CVD, with a focus on their clinical relevance, efficacy, safety, and future applications. Inclisiran, a siRNA targeting PCSK9, has recently entered clinical practice, offering effective LDL-C reduction with just twice-yearly dosing, an approach that may enhance long-term adherence and outcomes. Other RNA-based agents in clinical development target lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 (ANGPTL3), addressing lipid fractions that were previously difficult to modify. Additionally, RNA platforms are being explored to modulate inflammatory pathways implicated in plaque progression, such as IL-6 and NLRP3. These therapies present promising new options for high-risk patients, particularly those with statin intolerance, familial hypercholesterolemia, or elevated lipoprotein(a). As these agents progress throughClinicians should become familiar with this evolving class of treatments as they move from specialized use toward broader clinical adoption.