Clinical effects of apolipoprotein C3 inhibitors on triglyceride levels and pancreatitis risk: a systematic review and meta-analysis.

Abstract

Novel therapies targeting apolipoprotein C3 (apoC3) have recently emerged as promising treatment options for hypertriglyceridemia and have been evaluated in phase II and III randomized clinical trials. This study aimed to perform an updated meta-analysis to assess the effects of apoC3 inhibitors on triglyceride and apoC3 concentrations, as well as their impact on the risk of acute pancreatitis. We conducted a meta-analysis of randomized, placebo-controlled trials evaluating apoC3-targeting therapies, including antisense oligonucleotides and small interfering RNA. Outcomes of interest included changes in triglyceride and apoC3 levels and the incidence of acute pancreatitis. The analysis was performed in accordance with PRISMA recommendations. Fourteen randomized trials comprising 3,422 participants met the inclusion criteria. Treatment with apoC3 inhibitors resulted in significant reductions in triglyceride levels compared with placebo (mean difference -58.7%; 95% CI -62.3 to -55.1; I²=93.8%). Similarly, apoC3 concentrations were markedly decreased (mean difference -75.3%; 95% CI -80.3 to -70.3; I²=94.7%). In addition, these therapies were associated with a significantly lower risk of acute pancreatitis (odds ratio 0.20; 95% CI 0.10 to 0.40; I²=0%). ApoC3-targeting therapies significantly reduce triglyceride and apoC3 levels in patients with hypertriglyceridemia and are associated with a reduced incidence of acute pancreatitis, supporting their potential role as an effective therapeutic strategy in this high-risk population.