Recent Advances in the Management of Dyslipidemia: A Systematic Review

Abstract

Dyslipidemia refers to abnormal levels of lipids in the bloodstream, typically exhibiting an increased pattern. Total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TGs) are all contributing factors to this disorder. This leads to an increased risk of atherosclerosis and cardiovascular diseases, such as coronary artery disease, which elevates the likelihood of morbidity. Dyslipidemia can be managed via the use of numerous classes of drugs and treatments. The conventional pharmacological agents comprising 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, selective cholesterol absorption inhibitors, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), bile acid sequestrants, monoclonal antibodies, and nutritional supplementation, such as inhibitors of cholesterol synthesis and absorption, and promoters of LDL-C excretion, are also discussed. Furthermore, conventional pharmacological treatment of dyslipidemia may elicit a variety of adverse side effects that are detrimental to the quality of life of the user. These side effects include muscle pain, weakness, liver enzyme elevations, and hyperglycemia. This systematic review further analyzes the pharmacological actions of novel lipid-lowering agents such as adenosine triphosphate-citrate lyase inhibitors (ACLi), selective peroxisome proliferator-activated receptor alpha (PPARα) modulators, cholesteryl ester transfer protein inhibitors (CETPi), antisense oligonucleotides (ASO), and angiopoietin-like protein 3 inhibitors (ANGPTL3i) as well as their efficacy in treating dyslipidemia while sparing the user of potentially severe side effects. Compared to existing treatments, novel therapies have shown significantly greater effectiveness in managing dyslipidemia-related lipid profiles and exhibit fewer systemic adverse effects. Some of the recent therapies discussed are alternative treatments that offer patients promising efficacy and improved tolerability. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to ensure a robust and transparent search process, aiming to minimize bias and maximize the retrieval of pertinent studies for review. Thus, this systematic review provides an overview of current and novel treatments for dyslipidemia, describing their efficacy, mechanism of action, safety, and side effects. As experimental investigations and clinical research progress, there is a possibility that a combination of newly tested medications and traditional ones may emerge as a promising treatment option for dyslipidemia in the future.

Keywords: angiopoietin-like protein 3 inhibitors; antisense oligonucleotides; cholesteryl ester transfer protein inhibitors; dyslipidemia; proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors.

Figure 1. Pathophysiology of dyslipidemia

Image credit:  Moon, Julie, Huang, Jacky Xiao Feng, Yousaf, Adil.

Figure 2. Dyslipidemia’s effects leading to atherosclerosis and cardiovascular disease risk

Image credit: Moon, Julie, Huang, Jacky Xiao Feng.

Figure 3. The PRISMA flow diagram depicting the study selection process

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.