A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part I

Abstract

Hypercholesterolemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), affecting a significant proportion of the adult population worldwide. This narrative review provides a comprehensive and up-to-date overview of hyperlipidemia management, spanning from epidemiological trends and underlying pathophysiological mechanisms to the limitations of conventional therapies such as statins and ezetimibe. Particular emphasis is placed on cardiovascular risk assessment, current stratification tools, and international guideline-based interventions. The present paper, focusing primarily on the biological mechanisms of dyslipidemia and the clinical use of traditional lipid-lowering agents, serves as the first part of a two-part series, preceding a forthcoming review of novel pharmacological approaches. Our data synthesis is based on a structured literature search conducted across Google Scholar, PubMed, and Scopus, including studies published up to June 2025. The review also includes aspects related to non-pharmacological strategies, pharmacoeconomic considerations, and pharmacogenetic influences on treatment response. Ultimately, this work aims to equip clinicians with evidence-based, nuanced insights essential for optimizing lipid management and reducing cardiovascular risk, while setting the foundation for understanding how emerging therapies may overcome current therapeutic limitations.