Additive Effects of Ezetimibe and Statins in Managing Elevated LDL-C: An Approach to Reducing Cardiovascular Risk

Abstract

Elevated low-density lipoprotein cholesterol (LDL-C) is a key modifiable risk factor for cardiovascular disease. While statins are the cornerstone of LDL-C-lowering therapy, their long-term use may result in dose-dependent adverse effects. Ezetimibe, a Niemann– Pick C1-Like 1 inhibitor, reduces intestinal cholesterol absorption and complements the reduction of hepatic cholesterol synthesis achieved through statin therapy. Evidence from major trials, including IMPROVE-IT, SHARP, RACING, and EWTOPIA 75, demonstrates that combination therapy achieves greater LDL-C reduction and provides modest improvements in clinical outcomes compared with statin monotherapy, while maintaining a favorable safety profile. The early initiation of combination therapy may permit the use of lower statin doses, thereby reducing adverse effects such as insulin resistance and hepatotoxicity. The co-administration of ezetimibe with statins, when implemented alongside guideline-recommended strategies, represents a rational and patient-centered approach for high-risk individuals. This strategy offers enhanced lipid control and improved safety outcomes compared with statin monotherapy.