LDL-Cholesterol Lowering Therapies: An Update

Low-density lipoprotein-cholesterol (LDL-C) is a causal factor in atherosclerotic cardiovascular disease (ASCVD). Decades of genetic, epidemiological and randomised evidence support LDL-C reduction as a central strategy for cardiovascular risk reduction. Statins remain the first choice of LDL-C-lowering therapy due to their proven efficacy and favourable safety profile. However, therapeutic options have now expanded with widespread availability of other agents including ezetimibe, bempedoic acid and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. These can be prescribed alone or in combination with statins to help achieve optimal LDL-C targets. More recently, RNA-based therapies, oral small molecule inhibitors, and gene-editing strategies have emerged, which may offer even greater LDL-C reduction. As evidence increasingly supports a "lower is better" approach, combining established and novel therapies offers opportunities to optimise ASCVD prevention. This review summarises the evolving landscape of LDL-C-lowering therapies, highlighting their mechanisms, evidence base, and implications for clinical practice.