ANGPTL3 as a therapeutic target for treating homozygous familial hypercholesterolaemia: a shot in the arm for evinacumab

Graphical Abstract(A) Putative mode of action of evinacumab on metabolism of apoB-100-containing lipoproteins in HoFH. The increased activity of LPL and EL due to inhibition of ANGPTL3 with evinacumab results in enhanced lipolysis and remodelling of VLDL particles, with increased conversion to IDL particles; increased hepatic uptake of VLDL remnants and IDL particles; and decreased production of LDL particles. (B) Sequential scheme for the management of patients with HoFH including use of the anti-ANGPTL3 monoclonal antibody, evinacumab. aConsider the following treatment goals: (i) LDL-cholesterol <2.5 mmol/L (<100 mg/dL) without ASCVD or other major risk factors for ASCVD; (ii) LDL-cholesterol <1.8 mmol/L (<70 mg/dL) with imaging evidence of ASCVD alone or additional major risk factors for ASCVD; (iii) LDL-cholesterol <1.4 mmol/L (<55 mg/dL) with a previous ASCVD event. bIf there is an incremental reduction in LDL-cholesterol < 15%, consider stopping PCSK9-directed therapy, especially if there is a LDLR null/null mutation. cUse of lipoprotein apheresis depending on availability, patient preference, service expertise, and cost. dConsider in patients with rapidly progressive ASCVD, who are refractory to the above therapies or when lipoprotein apheresis and new drugs are not available.Open in new tabDownload slide