CURRENT ADVANCES IN LIPOPROTEIN(A) MANAGEMENT: CLINICAL SIGNIFICANCE AND EMERGING THERAPIES

Background: Lipoprotein(a) [Lp(a)] is an independent, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Despite its clinical importance, Lp(a) remains largely unaffected by traditional lipid-lowering therapies, contributing to significant residual cardiovascular risk. Aim: This review aims to synthesize current knowledge regarding the clinical significance of elevated lipoprotein(a) levels and to explore the landscape of emerging therapeutic strategies designed to specifically address this challenging cardiovascular risk factor. Materials and Methods: An extensive synthesis of the current literature, prioritizing comprehensive review articles and meta-analyses published within the last five years, was conducted using multiple electronic databases (PubMed, Scopus, Google Scholar). Results: Epidemiological data indicate that 20–30% of the global population has elevated Lp(a) levels (>30–50 mg/dL). While lifestyle and statins show negligible effects on Lp(a) concentration, novel nucleic acid-based therapies - specifically antisense oligonucleotides (pelacarsen) and small interfering RNAs (olpasiran, lepodisiran, zerlasiran) have demonstrated the ability to reduce Lp(a) levels by 70% to over 95%. Furthermore, oral small-molecule inhibitors like muvalaplin offer promising alternatives by disrupting the assembly of the Lp(a) particle. Conclusion: The emergence of targeted RNA-based and small-molecule therapies represents a paradigm shift in cardiovascular prevention. As phase 3 clinical trials progress, these interventions may provide the first definitive means of mitigating the residual risk associated with elevated Lp(a).