SAT-267 - Triglyceride Lowering Treatment with Apolipoprotein C3 Inhibitors and Pancreatitis: A Meta-Analysis of Randomized Trials

Background: Conventional triglyceride (TG) lowering therapies have limited effectiveness in treating hypertriglyceridemia and reducing risk of pancreatitis.

Objective: An updated study to evaluate the effectiveness and safety of apolipoprotein C3 (ApoC-3) inhibitors in primary or secondary hypertriglyceridemia.

Methods: 13 placebo controlled randomized trials evaluating ApoC-3 inhibitors (Olezarsen, Plozasiran, Volanesorsen) in patients with either primary or secondary hypertriglyceridemia were included (inception-December 2025). The co-primary outcomes were reduction in TGs and acute pancreatitis incidence (as defined in each trial). The secondary efficacy outcomes were changes in ApoC-3 levels, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, low density lipoprotein cholesterol (LDL-C). The safety outcomes were thrombocytopenia (platelet < 100,000), elevation in ALT or AST>3 times and serious adverse events (SAEs). The lipid levels were measured as change in least square means (LSM) unless reported otherwise by study. The outcomes were measured as random effect standardized mean difference (SMD) for continuous variable and risk ratios (RR) for binary outcomes with a 95% confidence interval (CI).

Results: The analysis comprised of 1,931 subjects with a median follow-up of 12 months. There was a significant 59% LSM reduction in TGs by ApoC-3 inhibitors (SDM: -0.71, -0.89 to -0.52, p< 0.001) vs. placebo along with a 79% relative risk reduction in acute pancreatitis with use of ApoC-3 inhibitors (RR: 0.21, 0.12-0.37, p< 0.001). The reduction in pancreatitis risk was strongest with olezarsen followed by plozasiran. ApoC-3 inhibitors in comparison to placebo reduced ApoC-3 levels by LSM 68.3 % (SMD: -0.72, -.091 to -0.52, p< 0.001) and non-HDL-C by LSM 24% (SMD: -0.55, -0.71 to -0.39, p< 0.001). The intervention arm led to significant increase in HDL-C by LSM 42% (SMD: 0.63, 0.44 to 0.81, p< 0.001) as well as LDL-C by LSM 46% (SMD: 0.44, 0.18 to 0.70, p=0.001). Regarding safety outcomes, no differences were observed for thrombocytopenia, elevation in ALT or AST>3 and SAEs. Subgroup analysis revealed significant increase in occurrence of thrombocytopenia with Volanesorsen.

Conclusion: ApoC-3 inhibitors significantly reduced TGs levels and risk of pancreatitis.

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