Apolipoprotein C-III inhibitors for the treatment of hypertriglyceridemia: a meta-analysis of randomized controlled trials

Abstract

Introduction

Hypertriglyceridemia is related to atherosclerotic cardiovascular risk and pancreatitis risk. The efficacy and safety of apolipoprotein C-III (APOC-III) inhibitors remains unclear.

Aim

To investigate the effects of APOC-III inhibitors on hypertriglyceridemia and its complications.

Methods

We systematically searched PubMed, Embase, and Cochrane Central databases from inception to May 2024 for randomized controlled trials (RCTs) comparing APOC-III inhibitors to placebo in patients with hypertriglyceridemia. We pooled percentage standardized mean difference (SMD) changes and risk ratio (RR) for continuous and binary outcomes, respectively, with 95 % confidence interval (CI). Subgroup analyses were performed with APOC-III inhibitors drugs doses (Olezarsen, Volanesorsen and Plozasiran), and primary and secondary hypertriglyceridemia.

Results

10 RCTs with 1204 participants were included, of which 46 % were men. APOC-III inhibitors significantly reduced triglycerides (TG) (SMD: −60.56 %; 95 % CI −68.94 to −52.18; p < 0.00001), APOC-III (SMD: −75.44 %; 95 % CI −80.81 to −70.07; p < 0.00001) and non-HDL-c (SMD: −27.49 %; 95 % CI −34.16 to −20.82; p < 0.00001) levels. Consistent results were found for all subgroup analyses. APOC-III inhibitors were capable to normalize TG levels in patients with severe hypertriglyceridemia (RR: 7.92; 95 % CI 4.12 to 15.23; p < 0.00001). There was a significant increase in HDL-c (SMD: 43.92 %; 95 % CI 37.27 to 50.57; p < 0.00001) and LDL-c (SMD: 33.05 %; 95 % CI 9.08 to 57.01; p = 0.007) levels. There was a significant relative risk reduction in acute pancreatitis in the APOC-III inhibitors group (RR 0.17; 95 % CI 0.05 to 0.53; p = 0.007). Adverse events were similar in both groups.

Conclusion

APOC-III inhibitors improve TG levels and other lipid panel parameters, as well as reduce episodes of acute pancreatitis in patients with primary and secondary hypertriglyceridemia.