Journal of Clinical Lipidology · Oct 26, 2026

The effect of evinacumab on the clinical outcomes of dyslipidemia: A systematic review of randomized controlled trials

By Shahid RS, Habib SM, Awan MZ et al.

BACKGROUND: Residual atherosclerotic cardiovascular disease risk remains substantial despite optimal conventional lipid-lowering therapy, particularly in patients with persistently elevated low-density lipoprotein cholesterol (LDL-C). Evinacumab, a monoclonal antibody targeting angiopoietin-like protein 3, represents a novel therapeutic approach that lowers LDL-C, triglycerides, apolipoprotein B (ApoB), apolipoprotein C-III (ApoC-III), and non-high-density lipoprotein cholesterol (non-HDL-C). OBJECTIVE: To systematically evaluate the efficacy and safety of Evinacumab, an ANGPTL3-targeting monoclonal antibody, in patients with dyslipidemia. This review and meta-analysis assesses its effects on lipid parameters, including LDL-C, triglycerides, ApoB, ApoC-III, and non-HDL-C. It also seeks to determine Evinacumab's potential role in reducing residual ASCVD risk across diverse dyslipidemic populations. METHODS: A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Embase, EBSCO, PubMed, ClinicalTrials.gov, the Cochrane Library, and gray literature sources were searched. Of 1718 identified records, 113 full-text articles were assessed, and 6 studies comprising 9 randomized clinical trials met the predefined eligibility criteria and were included. RESULTS: Evinacumab demonstrated substantial lipid-lowering efficacy across doses ranging from 5 to 20 mg/kg. LDL-C reductions ranged from approximately 16% to 50% over follow-up periods of 16 to 24 weeks, with consistent efficacy observed in patients with homozygous familial hypercholesterolemia, including pediatric populations, and in adults with refractory dyslipidemias. Clinically meaningful reductions were also reported for triglycerides, ApoB, ApoC-III, and non-HDL-C. Triglyceride lowering was particularly pronounced in patients with severe hypertriglyceridemia, supporting its potential role in reducing pancreatitis risk, although responses varied according to the underlying genetic etiology. Evinacumab was generally well tolerated, with no major treatment-related safety concerns. Some studies reported transient anti-drug antibodies, but they did not appear to compromise efficacy or safety. CONCLUSION: Evinacumab is an effective lipid-lowering therapy that produces clinically meaningful reductions in LDL-C, triglycerides, and apolipoproteins across difficult-to-treat dyslipidemic populations. Its favorable safety profile supports its use in refractory hypercholesterolemia and severe hypertriglyceridemia. Larger randomized trials with longer follow-up and head-to-head comparisons with other emerging lipid-lowering therapies are warranted to further define its long-term clinical role.

doi.org/10.1016/j.jacl.2026.10.011PubMed 42995029Interventions