Efficacy and Safety of Olezarsen in Dyslipidemia: A Systematic Review and Dose-response Meta-analysis of Randomized...

Olezarsen emerged as a novel promising Apo-C3 inhibitor for dyslipidemia. However, its dose-response relationship remains uncertain. This review aims to evaluate the lipid-lowering effect of olezarsen, safety measures, and dose-response effects to determine the optimal dose. A systematic search was conducted across Scopus, PubMed, Science-Direct, and CENTRAL on January 2, 2025. Randomized controlled trial (RCT) comparing olezarsen with placebo in dyslipidemia was included. The Rob 2.0 tool was implemented to assess quality. R-studio and STATA were used to conduct statistical analysis. From a total of 194 documents at initial search, four RCTs involving 361 patients were included in the present analysis. Olezarsen significantly reduces plasma Apo-C3 across all dosage cohorts, including a 50 mg dose (MD: -70.31 %; 95 % CI: -83.89 to -56.74; p < 0.01) and an 80 mg dose administered every four weeks. It also significantly lowered triglycerides at any dose level, with reductions observed at 50 mg (MD: -49.84 %; 95 % CI = -70.42 to -22.37; p = 0) and 80 mg (MD: -52.32 %; 95 % CI: -58.25 to -46.40; p < 0.01). Olezarsen has minimal effect on low-density lipoprotein (LDL) but significantly increases high-density lipoprotein (HDL). Dose-response meta-analysis modeling suggests that 50 mg administered every four weeks may represent the optimal dose, beyond which added benefits diminish. Safety analysis revealed tolerability in liver, renal, and hematological parameters. In conclusion, olezarsen is an effective Apo-C3 inhibitor that improves lipid profiles with a favorable safety profile. This modeling-based insight refines previous findings by delineating a clearer therapeutic window.