Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III (ApoC-III), offers a new and promising option for lowering triglyceride levels.<h4>Methods</h4>A systematic search of PubMed, Scopus, Web of Science, and Cochrane was conducted through September 2025 to identify randomized controlled trials (RCTs) comparing olezarsen with placebo in adults with hypertriglyceridemia at high cardiovascular risk. The gene discussed is APOC3; the disease is hypertriglyceridemia.