Abstract Background and aims Small dense LDL (sd-LDL) is a highly atherogenic LDL subfraction characterized by smaller particle size, increased density, enhanced arterial wall penetration, greater susceptibility to oxidation, and increased macrophage uptake. We evaluated pharmacological interventions for elevated sd-LDL. Methods Between July 2023 and September 2025, 126 patients with elevated sd-LDL who either initiated lipid-lowering therapy or underwent modifications to their lipid-lowering regimen were included. The lipid-lowering therapies used included statins, fibrates, ezetimibe, and eicosapentaenoic acid/docosa hexaenoic acid (EPA/DHA). Pre-and post-treatment values for sd-LDL and other lipid parameters were analyzed for each therapy group. Results Statins significantly reduced sd-LDL (–44.0%, p0.001), LDL (–40.1%, p0.001), HDL (–13.8%, p=0.011), total cholesterol (TCHO; –28.0%, p0.001), L/H ratio (–34.8%, p0.001), and non-HDL cholesterol (–34.5%, p0.001). TG reduction was not significant (–2.0%, p=0.248). Ezetimibe also significantly lowered sd-LDL (–33.3%, p0.001), LDL (–29.6%, p0.001), TCHO (–16.8%, p=0.001), L/H ratio (–31.6%, p0.001), non-HDL cholesterol (–26.6%, p0.001), and TG (–19.1%, p=0.010). HDL increased slightly (+7.4%, p=0.409). Fibrates produced a significant reduction in sd-LDL (–21.8%, p0.001) and TG (–32.4%, p=0.003), while changes in other parameters were not statistically significant. EPA/DHA showed no significant changes in any lipid marker. Conclusions Statins and ezetimibe are most effective for lowering sd-LDL and other atherogenic lipids in high sd-LDL cholesteremia. Fibrates are preferable for patients with high sd-LDL cholesteremia accompanied by elevated TG, while EPA/DHA had no significant effect on this dataset. Conflict of interest Nothing to disclose
Suzuki et al. (Fri,) studied this question.