Key result
ApoCIII, ANGPTL3/4, and FGF21 therapies lower remnant cholesterol ~50-80%, potentially reducing ASCVD risk if apoB drops.
Why the study?
Elevated remnant cholesterol is causally linked to ASCVD, but the feasibility and requirements for remnant cholesterol-lowering therapies to provide clinical cardiovascular benefit remain to be determined.
Do remnant cholesterol lowering therapies (apoCIII inhibitors, ANGPTL3/4 inhibitors, FGF21 analogues) reduce ASCVD risk in patients with elevated triglycerides and residual risk despite statin therapy?
Do remnant cholesterol lowering therapies (apoCIII inhibitors, ANGPTL3/4 inhibitors, FGF21 analogues) reduce ASCVD risk in patients with elevated triglycerides and residual risk despite statin therapy?
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Novel therapies targeting remnant cholesterol show profound lipid-lowering efficacy (50-80% reduction) and represent a promising future target for ASCVD prevention in patients with residual risk despite statin therapy.
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 50 to 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.
Wulff et al. (2026) studied this question. Inhibitors of apoCIII, ANGPTL3/4, and FGF21 analogues can lower remnant cholesterol by 50-80%, potentially reducing ASCVD risk if apoB lipoproteins also decrease.
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