Is there still a place for fenofibrate-statin combination therapy?

Abstract

Although low-density lipoprotein cholesterol (LDL-C) is the main target for the prevention of atherosclerotic cardiovascular disease (ASCVD), hypertriglyceridaemia (HTG), a common condition characterised by elevated blood triglyceride (TG) levels, contributes to residual cardiovascular risk independently of LDL-C levels. Elevated TG levels are a feature of atherogenic dyslipidaemia, which also includes low HDL-C levels and high levels of atherogenic small, dense LDL, together with accumulation of atherogenic remnant particles. Treatment of HTG includes lifestyle interventions, but these are not always sufficient to significantly reduce TG levels in people at high cardiovascular risk. Current guidelines for the treatment of dyslipidaemias recommend the use of statins as the first choice in people with HTG (TG >200 mg/dL) and high CV risk, and consideration of the use of specific TG-lowering drugs, such as fenofibrate, bezafibrate or icosapent ethyl if HTG persists. Fenofibrate acts by activating the peroxisome proliferator receptor alpha (PPARα), a nuclear receptor that plays an important role in lipid and lipoprotein metabolism, glucose homeostasis and inflammation. Several clinical trials have shown that fibrates may reduce the incidence of major cardiovascular events only in patients with high TG levels and low HDL-C levels, a finding that was also observed with fenofibrate in combination with a statin compared to statin therapy alone. The recent failure of the PROMINENT trial with pemafibrate in combination with a statin highlighted the notion that treatment with fibrates provides a clinical benefit only if they lower apoB levels.