Olezarsen for Hypertriglyceridemia: A New Therapy Update with Systematic Review and Meta-Analysis

Hypertriglyceridemia is a frequently seen lipid disorder. It is linked to a higher risk of cardiovascular diseases and adds a significant burden on healthcare systems. Olezarsen, a novel antisense therapy targeting apolipoprotein C-III, offers effective triglyceride reduction with the convenience of infrequent dosing. This meta-analysis evaluates the safety and efficacy of olezarsen in hypertriglyceridemia to guide clinical decision-making. A comprehensive literature search across major databases identified randomized control trials comparing olezarsen with usual care in patients with hypertriglyceridemia. Data extraction and bias assessment were conducted independently, using RoB 2.0 and the GRADE framework. A meta-analysis was performed using RevMan 5.4.1, applying random effects models and assessing heterogeneity with the I2 statistic. Eight randomized controlled trials were included. Olezarsen significantly reduced triglycerides (MD -58.57, 95% CI -63.10 to -54.04; I2 = 13%) and apolipoprotein C-III (MD -69.81, 95% CI -75.77 to -63.84; I2 = 56%). Significant improvements were also observed in apolipoprotein B, nonhigh-density lipoprotein cholesterol, and achievement of TAG targets (<150 mg/dL). There was no increase in overall or serious adverse events, although injection-site reactions, liver enzyme elevations, and treatment discontinuation were higher with olezarsen. Olezarsen significantly improves TAG levels and atherogenic lipid parameters in patients with hypertriglyceridemia, demonstrating robust efficacy across multiple outcomes. It maintains an overall favorable safety profile, supporting its role as a promising therapeutic option, although monitoring for liver enzymes and injection-site reactions is warranted.