Efficacy and Safety of Combined Lipid-Lowering Therapy in Patients With Mixed Dyslipidemia: Data From a Survey of Expert Lipidologists

Highlights Mixed dyslipidemia is an aggressive atherogenic phenotype that increases cardiovascular risk. When controlling LDL cholesterol with statins, there remains a high “residual” risk due to hypertriglyceridemia. The use of non‑statin drugs (fenofibrate, omega-3 PUFA) in combinations is limited by doctors’ concerns about safety. Background . Mixed dyslipidemia (MDL) is a common, aggressive, atherogenic lipid phenotype characterized by a simultaneous increase in triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol and a decrease in high-density lipoprotein cholesterol (HDL-C) against a background of frequently elevated low-density lipoprotein cholesterol (LDL-C). Despite the dominant role of statins in reducing cardiovascular risk, the residual risk associated with uncontrolled hypertriglyceridemia remains high in patients with MDL, despite statin therapy and the potential achievement of LDL-C goals. This necessitates the use of non-statin medications to correct hypertriglyceridemia. The drugs most frequently prescribed for the correction of hypertriglyceridemia are fenofibrate, a representative of the fibrate class, which has been studied most thoroughly and has shown its effectiveness in correcting residual risk, and the drug omega-3 polyunsaturated fatty acids (LP omega-3 PUFA, Omacor). However, their use in combination with other lipid-lowering medications (statins, ezetimibe, bempedoic acid) raises concerns among physicians in real-world clinical practice due to safety concerns for patients taking this combination. Aim. To evaluate the real-world use of medications for the correction of hyperglycemia (fenofibibrate and/or omega-3 PUFA) and their combinations with other lipid-lowering medications based on a survey of leading Russian lipidology experts. Methods. In November 2025, an interactive survey on the safe use of combination lipid-lowering therapy was conducted as part of a speaker forum of leading lipidology specialists from various regions of Russia (54 experts). Results. The majority (93%) of experts indicate the need for long-term/lifelong/indefinite prescription of triglyceride-lowering medications. Moreover, 87% of experts indicate that “indefinitely” is the correct term. 72% of experts believe that therapy in patients with type 2 diabetes and high LDL-C and TG levels should be initiated with a statin + fenofibrate combination to protect against cardiovascular and microvascular complications. When asked about the proportion of patients requiring three or more lipid-lowering medications as part of routine treatment, 70% of experts indicated a value of up to 20%, while 30% indicated a value of 20–40%. When asked about the frequency of true statin intolerance in routine practice, all experts (100%) responded: up to 10%. In a clinical situation where a patient with high cardiovascular risk, while prescribed rosuvastatin 10 mg, has LDL-C levels reaching 2.0 mmol/L and TG levels remaining at 3.0 mmol/L, 57% of experts would add fenofibrate to therapy and choose a fixed-dose combination (rosuvastatin + fenofibrate, Suprosafen). 11–17% of experts indicated the appropriateness of increasing the rosuvastatin dose to 20 mg, adding ezetimibe to rosuvastatin, or combining fenofibrate and ezetimibe (a triple combination). Conclusion . Thus, leading Russian lipidologists are actively prescribing dual and triple combinations of lipid-lowering drugs aimed at more effectively correcting not only LDL-C levels but also TG and TG-rich particles. The implementation of personalized algorithms taking into account the safety profile will optimize the treatment of patients with mixed DLP and minimize the risks of therapy.