Angiopoietin-like protein 3 (ANGPTL3) and
apolipoprotein C-III (
apoC-III) are novel metabolic targets for correcting hypertriglyceridaemia (HTG). As a background to their potential clinical use, we review the metabolic aetiology of HTG, particular abnormalities in
triglyceride-rich
lipoproteins (TRLs) and their role in atherosclerotic
cardiovascular disease (ASCVD) and
acute pancreatitis. Molecular and cardiometabolic aspects of ANGPTL3 and
apoC-III, as well as inhibition of these targets with
monoclonal antibody and
nucleic acid therapies, are summarized as background information to descriptions and analyses of recent clinical trials. These studies suggest that ANGPTL3 and
apoC-III inhibitors are equally potent in lowering elevated plasma
triglycerides and TRLs across a wide range of concentrations, with possibly greater efficacy with inhibition of
apoC-III. ANGPTL3 inhibition may, however, have the advantage of greater lowering of plasma
LDL cholesterol and could specifically address elevated
LDL cholesterol in familial hypercholesterolaemia refractory to standard
drug therapies. Large clinical outcome trials in relevant populations are still required to confirm the long-term efficacy, safety and cost effectiveness of these potent agents for mitigating the complications of HTG. Beyond targeting severe chylomicronaemia in the prevention of
acute pancreatitis, both agents could be useful in addressing residual risk of ASCVD due to TRLs in patients receiving best standard of care, including behavioural modifications,
statins,
ezetimibe,
fibrates and
proprotein convertase subtilisin/kexin type 9 inhibitors.