“…[20][21][22] Importantly, they also experience significant dyshomeostasis in lipid metabolism, leading to potentially modifiable atherosclerotic risks, including poor clearance of circulating triglycerides and lipoproteins, reduced lipoprotein lipase activity, increased oxidation of LDL cholesterol, and possibly, increased relative cholesterol absorption. [23][24][25][26] In the IMPROVE-IT, compared with simvastatin monotherapy, individuals randomized to combination therapy with ezetimibe plus simvastatin experienced a greater mean reduction in both LDL cholesterol and triglycerides across all levels of eGFR. Because individuals with CKD are an inherently higher-risk group, achieving the same absolute level of reduction in LDL cholesterol through both inhibition of cholesterol synthesis and cholesterol absorption may be more effective in risk mitigation; however, considering the numerous mechanisms by which CKD leads to increased cardiovascular risk, the relative benefit that we observed from combination therapy as eGFR declined could also suggest that ezetimibe add-on therapy conferred pleiotropic effects beyond LDL cholesterol or triglyceride reduction alone.…”