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Published on: January 28, 2021
Apolipoprotein C-III inhibitors for the treatment of hypertriglyceridemia: a meta-analysis of randomized controlled
Mariana de Moura de Souza1, Beatriz Ximenes Mendes2, Maria Luiza Rodrigues Defante3
1Department of Internal Medicine, Federal University of Paraná, Brazil.
Insights
Apolipoprotein C-III (APOC-III) inhibitors significantly reduce triglycerides and lower pancreatitis risk in hypertriglyceridemia patients. These findings highlight APOC-III inhibitors as a promising treatment for managing high triglyceride levels and associated complications.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Pharmacology
Background:
- Hypertriglyceridemia is a significant risk factor for atherosclerotic cardiovascular disease and acute pancreatitis.
- The clinical efficacy and safety profile of apolipoprotein C-III (APOC-III) inhibitors for managing hypertriglyceridemia remain incompletely understood.
Purpose of the Study:
- To systematically evaluate the effects of APOC-III inhibitors on triglyceride levels and associated complications in patients with hypertriglyceridemia.
- To assess the safety and efficacy of APOC-III inhibitors across different drug doses and types of hypertriglyceridemia.
Main Methods:
- A systematic literature search was conducted across PubMed, Embase, and Cochrane Central databases up to May 2024.
- Included were randomized controlled trials (RCTs) comparing APOC-III inhibitors with placebo in hypertriglyceridemia patients.
- Data were pooled using standardized mean differences (SMD) for continuous outcomes and risk ratios (RR) for binary outcomes, with subgroup analyses based on drug specifics and hypertriglyceridemia type.
Main Results:
- Ten RCTs involving 1204 participants demonstrated that APOC-III inhibitors significantly reduce triglycerides (SMD: -60.56%), APOC-III levels (SMD: -75.44%), and non-HDL-c (SMD: -27.49%).
- APOC-III inhibitors were effective in normalizing triglyceride levels in severe hypertriglyceridemia cases (RR: 7.92) and increased HDL-c and LDL-c levels.
- A significant reduction in the relative risk of acute pancreatitis was observed (RR: 0.17), with similar adverse event profiles between treatment and placebo groups.
Conclusions:
- APOC-III inhibitors demonstrate significant efficacy in improving triglyceride levels and lipid profiles in patients with both primary and secondary hypertriglyceridemia.
- These agents effectively reduce the risk of acute pancreatitis, a serious complication of hypertriglyceridemia.
- The findings support APOC-III inhibitors as a valuable therapeutic option for managing hypertriglyceridemia and its associated cardiovascular and pancreatic risks.
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.
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