Feasibility of remnant cholesterol as a therapeutic target for atherosclerotic cardio-vascular disease

Observational epidemiological and genetic studies strongly indicate that elevated remnant cholesterol is a causal risk factor for ASCVD. In randomized controlled trials of individuals with elevated plasma triglyceride levels up to 10 mmol/L (880 mg/dL), apoCIII and ANGPTL3 and 4 inhibitors and FGF21 analogues lower remnant cholesterol levels by 50-80%, and large cardiovascular outcome trials of these novel drugs are therefore well positioned to provide definitive evidence of clinical benefit. However, for these trials to succeed, lowering of remnant cholesterol must be accompanied by a lowering of total apolipoprotein B containing lipoproteins. If such trials succeed, remnant cholesterol lowering may become an important target for ASCVD prevention among patients with residual ASCVD risk due to elevated non-HDL cholesterol levels despite statin therapy.