Lower, Earlier, Longer and Personalized: Rethinking Lipid-Lowering Therapy for Cardiovascular Prevention

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Lipid-lowering therapy represents the cornerstone of cardiovascular prevention, with low-density lipoproteins (LDL) identified as a causal factor in atherosclerosis. Last decades have seen a rapid expansion in therapeutic options beyond statins, including ezetimibe, bempedoic acid, proprotein convertase subtilisin/kexin Type 9 inhibitors, both monoclonal antibodies and small interfering RNA therapies, and emerging agents targeting novel pathways. Current treatment paradigms emphasize early risk stratification, aggressive LDL-cholesterol (LDL-C) control in high-risk individuals and systematic combination therapy when treatment goals cannot be achieved with statins alone. In addition, growing attention is being paid to residual cardiovascular risk associated with triglyceride-rich lipoproteins and lipoprotein (a) [Lp(a)]. Novel pharmacological approaches targeting these pathways are currently under investigation and may substantially modify the future landscape of lipid management. This review summarizes current strategies for lipid-lowering therapy across different cardiovascular risk categories and discusses emerging therapies targeting LDL-C, triglyceride-rich lipoproteins and Lp(a), highlighting future directions in precision lipidology.