Efficacy and Safety of Olezarsen in Patients With Hypertriglyceridemia: A Meta-Analysis of Randomized Controlled Trials.

Aims: Novel drugs that target apoC-III in lipoprotein metabolism to reduce plasma triglycerides are currently under development. Olezarsen, a drug similar to its predecessor, volanesorsen, is in Phase 3 trials. A meta-analysis of RCTs was done to study its effect on hypertriglyceridemia. Material and Methods: Screening was done on PubMed, Embase, Scopus, and the Cochrane Library from inception to August 2024. We used Review Manager (Version 5.4) for statistical analysis. Subgroups of olezarsen at doses of 10, 50, and 80 mg were made. Continuous outcomes were reported as mean differences with 95% CIs. Adverse events were reported using risk ratios and 95% CIs. The risk of bias was analyzed using the Cochrane risk of bias tool. Results: Four RCTs with 374 participants, 278 in intervention and 96 placebo controls, were included. At all doses of olezarsen, a significant reduction in fasting triglyceride levels (MD: 45.69; 95% CI: 35.84, 55.54; p < 0.00001) was seen. This was most pronounced at 80 mg dose (MD: 51.98 95% CI: 43.06, 60.90; p < 0.00001). A reduction in apoC-III (MD: 58.77; 95% CI: 35.94, 81.61; p < 0.00001) and an increase in HDL (MD: 0.21; 95% CI: 0.04, 0.37; p = 0.01) were also observed. No significant effect was observed on LDL levels (MD: -0.13; 95% CI: -0.40, 0.14; p = 0.34). Overall, no significant adverse effects were seen compared to placebo (RR: 1.42; 95% CI: 0.66, 3.05; p = 0.37). Conclusion: Olezarsen showed remarkable efficacy in lowering triglycerides, with a dose-dependent effect, while significantly increasing HDL levels and reducing apoC-III. Its safety profile is commendable. Although it performed well compared to volanesorsen, inconsistencies in LDL reduction and heterogeneity in some groups warrant further large-scale RCTs to better assess its safety and efficacy. Clinical decisions should be tailored to individual patient profiles, as hypertriglyceridemia management may vary on a case-to-case basis.