Efficacy and Safety of Apolipoprotein C‐ III Inhibitors in Hypertriglyceridemia: A Network Meta‐Analysis of Randomised Controlled Trials

BACKGROUND: Hypertriglyceridemia is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the efficacy and safety of apolipoprotein C-III (ApoC-III) inhibitors in patients with hypertriglyceridemia. METHODS: Electronic databases were systematically searched for randomised controlled trials (RCTs) comparing ApoC-III inhibitors (Volanesorsen, Olezarsen and Plozasiran) with placebo. A frequentist network meta-analysis was performed. Continuous outcomes were presented as mean differences (MDs), and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs). RESULTS: A total of 15 RCTs involving 3934 patients were included. All ApoC-III inhibitors demonstrated significant reductions in TG, except for Volanesorsen 100 mg Q1W and Olezarsen 10 mg Q4W. Olezarsen 80 mg administered every 4 weeks had the highest SUCRA ranking for TG reduction (MD: -63.26; 95% CI: -70.04 to -56.47; p < 0.01). Moreover, ApoC-III inhibitors were associated with a significant reduction in the incidence of pancreatitis (HR: 0.16, 95% CI: 0.07-0.33, p < 0.01). None of the agents significantly increased the risk of serious adverse events. CONCLUSIONS: ApoC-III inhibitors significantly improved triglyceride levels and other lipid parameters and, most importantly, substantially reduced the risk of acute pancreatitis. Future trials are needed to evaluate their effects on cardiovascular outcomes.