Expert Opin Ther Targets. 2026 Feb 27. doi: 10.1080/14728222.2026.2639678. Online ahead of print.
ABSTRACT
INTRODUCTION: Elevated plasma concentration of remnant cholesterol, the cholesterol in triglyceride-rich lipoproteins, is associated with increased risk of atherosclerotic cardiovascular disease(ASCVD) in large observational epidemiological and Mendelian randomization studies. Novel drugs with pronounced remnant cholesterol-lowering effects are being developed; however, their effect on risk of ASCVD remains to be documented.
AREAS COVERED: Observational epidemiological and Mendelian randomization studies and randomized controlled trials examining plasma remnant cholesterol levels as an emerging drug target for ASCVD prevention.
EXPERT OPINION: 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.
PMID:41758338 | DOI:10.1080/14728222.2026.2639678