Evinacumab Across Different Lipid Phenotypes: A Systematic Review and Meta-Analysis

INTRODUCTION: Evinacumab, a monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3), has emerged as a promising therapeutic option for severe dyslipidemias. We have conducted a systematic review to evaluate its efficacy across different clinical settings. METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42026142022). Eligible studies included randomized controlled trials, open-label extension studies, single-arm studies, and observational cohorts involving healthy individuals and patients with hypercholesterolemia or hypertriglyceridemia. Due to the small number of available studies and the absence of the data required for quantitative pooling in other clinical settings, a single-arm meta-analysis was performed exclusively in patients with hypercholesterolemia receiving evinacumab 15 mg/kg every 4 weeks. RESULTS: Overall, 17 studies were included in the systematic review. In hypercholesterolemia, evinacumab consistently reduced LDL-C levels by approximately 50%, with reductions ranging from 42% to 82% across studies. Long-term extension and real-world data confirmed sustained efficacy. Meta-analysis of seven studies including 357 patients receiving evinacumab 15 mg/kg intravenously every 4 weeks demonstrated significant reductions in LDL-C [mean difference (MD) - 48.56%], non-HDL-C (MD - 50.19%), apolipoprotein B (MD - 40.51%), and triglycerides (MD - 53.13%). In hypertriglyceridemia, qualitative evidence showed marked triglyceride lowering, particularly in multifactorial chylomicronemia syndrome, with reductions frequently exceeding 60-80%, whereas responses were limited in familial chylomicronemia syndrome. CONCLUSIONS: Evinacumab provides substantial and sustained lipid-lowering effects, particularly in homozygous familial hypercholesterolemia. Emerging evidence also supports a potential role in severe hypertriglyceridemia, although further studies are needed to define its clinical benefits in this setting.