Managing remnant cholesterol: role of fenofibrate–statin therapy in reducing triglyceride-rich lipoproteins
(2026) Frontiers in Cardiovascular Medicine — Vol. 13, p. 1837004 [1-13] (2026)
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- (en) MP (2026) Managing remnant cholesterol: role of fenofibrate-statin therapy in reducing triglyceride-rich lipoproteins. Dyslipidemia, a key risk factor for atherosclerotic cardiovascular disease (ASCVD), is conventionally managed by lowering low-density lipoprotein cholesterol (LDL-C) level. However, even with on-target LDL-C and optimal control of traditional risk factors such as hypertension and diabetes, a substantial residual risk of major adverse cardiovascular events (MACE) persists. A growing body of evidence suggests that remnant cholesterol (RC)-the cholesterol content of triglyceride-rich lipoproteins (TRLs)-partially contributes to this residual risk. Consequently, non-high-density lipoprotein cholesterol (non-HDL-C) is considered a better measure of the ASCVD risk and a comprehensive treatment goal for dyslipidemia. Statin therapy, the standard care for dyslipidemia management, falls short of mitigating RC-related residual risk. The global rise in obesity, type 2 diabetes, and metabolic syndrome has led to a growing prevalence of hypertriglyceridemia, underscoring the need for adjunctive therapies that target TRLs and lower non-HDL-C levels. Fenofibrate, a well-established TRL-lowering agent, has demonstrated efficacy in reducing non-HDL-C when used in combination with statins. Evidence from clinical trials and real-world studies suggests potential benefits of this combination in reducing cardiovascular risk, particularly in patients with elevated triglyceride levels. Moreover, long-term studies-spanning up to two decades-have affirmed the safety and tolerability of fenofibrate, reinforcing its role as a valuable add-on therapy to address remnant cholesterol and residual cardiovascular risk. Frontiers in Cardiovascular Medicine 01 frontiersin.org GRAPHICAL ABSTRACT Efficacy of fenofibrate-statin combination therapy in managing remnant cholesterol and CVD risk. Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins (TRLs), is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and partly contributes to the residual cardiovascular disease (CVD) risk in patients even with at-target low-density lipoprotein cholesterol (LDL-C). Fenofibrate in combination with statins is an efficacious strategy to reduce RC levels in addition to non-high density lipoprotein cholesterol (non-HDL-C) for managing residual CVD risk in statin-treated patients. Rosu + FF, Rosuvastatin and fenofibrate combination; Sim + FF, Simvastatin and fenofibrate combination; Atv + FF, Atorvastatin and fenofibrate combination; %WM, percent weighted mean.
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Raja, V., Aguiar, C., Alsayed, N., Chibber, Y., Elbadawi, H., Farnier, M., Pushpa, K., Tokgözoglu, L., Zambon, A., Berrou, J.-P., & Hermans, M. (2026). Managing remnant cholesterol: role of fenofibrate–statin therapy in reducing triglyceride-rich lipoproteins. Frontiers in Cardiovascular Medicine, 13, 1837004 [1-13]. https://doi.org/10.3389/fcvm.2026.1837004 (Original work published 2026)