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.

Keywords: cardiovascular risk reduction; emerging therapies for dyslipidemia; ezetimibe; hypercholesterolemia; lipid-lowering therapies; statins.

Figure 1

Risk factors of hyperlipidemia. Abbreviations: CKD—Chronic kidney disease; COPD—Chronic Obstructive Pulmonary Disease; IBD—Inflammatory Bowel Disease; PCOS—Polycystic ovary syndrome.

Figure 2

Lipid metabolism. 1. Transport of exogenous lipids via chylomicrons to peripheral tissues; 2. De novo synthesis of cholesterol. Transport of cholesterol via VLDL to peripheral tissues; 3. Transport of excess cholesterol via HDL back to the liver. Abbreviations: TG—Triglycerides; CoA—Coenzyme A; VLDL—Very low density lipoprotein; LDL—Low density lipoprotein; IDL—Intermediate density lipoprotein; HDL—High density lipoprotein; MTP—Microsomal triglyceride transfer protein; ACL—Adenosin triphosphate-citrate lyase; HMG-CoA reductase—Hydroxymethylglutaryl-CoA reductase; LPL- Lipoprotein lypase; PCSK9—Proprotein convertase subtilisin/kexin type 9; ABCA1—ATP-binding cassette transporter A1.