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.