NOVEL DIRECTIONS IN LIPID-LOWERING THERAPY FOR THE PREVENTION OF CARDIOVASCULAR DISEASES

Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide despite significant advances in preventive cardiology. Dyslipidemia is one of the most important modifiable risk factors contributing to the development and progression of atherosclerotic cardiovascular disease. While statins continue to represent the cornerstone of lipid-lowering therapy, a substantial proportion of high-risk patients fail to achieve recommended low-density lipoprotein cholesterol targets or experience recurrent cardiovascular events despite optimal treatment. Recent years have witnessed remarkable progress in the development of novel lipid-lowering agents that target different pathways of lipoprotein metabolism, offering improved efficacy and longterm cardiovascular protection. Emerging therapeutic strategies include proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, small interfering RNA (siRNA)-based therapies such as inclisiran, adenosine triphosphate citrate lyase inhibitors represented by bempedoic acid, and innovative approaches targeting lipoprotein(a), angiopoietinlike protein 3, and apolipoprotein C-III. These therapies not only achieve profound reductions in LDL-C but also address residual cardiovascular risk that persists despite intensive statin therapy. Furthermore, advances in precision medicine, genetic profiling, and artificial intelligence have facilitated individualized lipid management strategies, improving patient adherence and optimizing clinical outcomes. This review summarizes current evidence regarding novel lipid-lowering therapies, their mechanisms of action, clinical efficacy, safety profiles, and future perspectives in the prevention of cardiovascular diseases.