Efficacy and safety of antisense oligonucleotide therapies targeting APoC-III in patients with severe hypertriglyceridemia: a meta-analysis of randomized controlled trials
Recommended Citation
Masood A, Qureshi AUH, Khalid Z, Shahid H, Malik ARK, Javed S, Mandahar M, Amanullah A, Siddiqui Y, Anwar T, Sohail A, Ayyan M, Qureshi MA. Efficacy and safety of antisense oligonucleotide therapies targeting APoC-III in patients with severe hypertriglyceridemia: a meta-analysis of randomized controlled trials. Monaldi Arch Chest Dis. 2026.
Document Type
Article
Publication Date
2-23-2026
Publication Title
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Universita di Napoli, Secondo ateneo
Keywords
Hypertriglyceridemia; antisense oligonucleotides; cardiovascular risk
Abstract
Hypertriglyceridemia (HTG) increases cardiovascular and pancreatitis risk. Antisense oligonucleotide (ASO) therapies like volanesorsen and olezarsen target ApoC-III mRNA to reduce ApoC-III, enhancing lipoprotein lipase activity and lowering triglycerides (TGs). This meta-analysis evaluates the efficacy and safety of these ASOs in severe HTG. A systematic review (PROSPERO: CRD42024577110) was conducted following PRISMA, sourcing studies from PubMed, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov until July 2024. Randomized controlled trials (RCTs) involving severe HTG (≥200 mg/dL) treated with volanesorsen or olezarsen vs. placebo were included. Data were synthesized using a random effects model in RevMan 5.4, and bias was assessed with the Cochrane tool. Of 31 identified articles, 9 RCTs (341 patients treated with ASOs, 209 controls) were included. ASOs significantly reduced TG levels [mean difference (MD): -53.72; 95% confidence interval (CI): -77.04 to -30.40; p< 0.00001]. Reductions were also seen in very low-density lipoprotein cholesterol (MD: -55.76; p< 0.00001), ApoC-III (MD: -74.78; p< 0.00001), and APOB48 (MD: -69.45; p< 0.00001). Olezarsen uniquely reduced APOB (MD: -15.60; p< 0.00001). Non-high-density lipoprotein cholesterol (HDL-C) decreased (MD: -23.25; p< 0.00001), while HDL-C increased (MD: +42.14; p< 0.00001). Volanesorsen was linked to higher low-density lipoprotein-cholesterol (MD: +62.74; p=0.004). For safety, local injection reactions, thrombocytopenia, and nausea were more common with volanesorsen. Acute pancreatitis occurred only in the placebo group (relative risk: 0.15; p=0.0004), indicating ASO protection. This meta-analysis confirms that ASOs effectively lower TGs and improve lipid profiles in severe HTG.
PubMed ID
41755797
ePublication
ePub ahead of print
