Safety and efficacy of antisense oligonucleotides on triglyceride, apolipoprotein C-III, and other lipid parameters levels in hypertriglyceridemia; a network meta-analysis of randomized controlled trials

Mahmoud, Abdelrahman; Abdelsayed, Kerollos; Mohamed, Ahmed Almahdy; Najah, Qasi; Abdulkader, Anas; Ali, Karim; Tabassum, Shehroze; Abouzid, Mohamed Riad; Abdelazeem, Basel; Mills, James D.

doi:10.1186/s12944-024-02389-2

Lipids in Health and Disease

Table 1 Summary characteristics of included studies

From: Safety and efficacy of antisense oligonucleotides on triglyceride, apolipoprotein C-III, and other lipid parameters levels in hypertriglyceridemia; a network meta-analysis of randomized controlled trials

Study ID	Used drug	Setting (center, country)	RCT phase	Sample size	Additional hyperlipidemia medications	Conclusion in brief
Ballantyne et al. 2024 [42]	Plozasiran	Multinational	Phase 2b	353	Statin, fibrate, n − 3 fatty acids, icosapent ethyl, and PCSK9 inhibitor	Plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks
Bergmark et al. 2024 [43]	Olezarsen	Multinational	Phase 2b	154	Statin, ezetimibe, fibrate, n − 3 fatty acids, niacin, PCSK9 inhibitor	In patients with moderate hypertriglyceridemia and elevated cardiovascular risk, olezarsen significantly reduced triglycerides, and apolipoprotein B, without major safety concerns.
Stroes et al. 2024 [40]	Olezarsen	Multinational	phase 3	66	Statin, fibrate, omega − 3 fatty acids	Olezarsen could offer a new treatment option for reducing plasma triglyceride levels in patients with familial chylomicronemia syndrome.
Tardif et al. 2022 [41]	Olezarsen	Multinational	Phase 2b	114	Statin, ezetimibe, fibrate, omega − 3 fatty acids, niacin, and PCSK9 inhibitor	Olezarsen significantly lowered triglycerides and atherogenic lipoproteins in patients with moderate hypertriglyceridemia and high or established cardiovascular disease risk.
Gaudet et al. 2024 [21]	Plozasiran	Multinational	phase 2b	229	Statin, fibrate, omega − 3 fatty acids, PCSK9 inhibitor	Plozasiran lowered triglycerides below the acute pancreatitis risk level and improved triglyceride-related lipoprotein and safety was favorable. Further studies are needed.
Gaudet et al. 2023 [38]	Plozasiran	Multinational	phase 1	52	Statin, ezetimibe, fibrates, omega-3 fatty acids	No significant toxicities or side effects were reported. Positive changes in lipid parameters were observed in the small patient cohorts, laying the groundwork for larger and longer trials
Gaudet et al. 2014 [16]	Volanesorsen	Multinational	phase 2	57	Statins and fibrates	Treatment with Volanesorsen significantly lowered triglyceride levels in patients with a variety of starting triglyceride levels.
Gouni et al. 2021 [39]	Volanesorsen	Multinational	phase 3	113	Statin, fibrate, fish oils, and ezetimibe	Volanesorsen significantly reduced triglyceride concentrations in patients with multifactorial chylomicronemia and might reduce acute pancreatitis events in these patients.
Oral et al. 2022 [31]	Volanesorsen	Multinational	phase 2	40	Statin, fibrates, and fish oil	Volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis in patients with FPLD.
Witztum et al. 2019 [29]	Volanesorsen	Multinational	phase 3	66	N − 3 fatty acids, statins, and fibrates	Volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome. Thrombocytopenia and injection site reactions were common adverse events.

FPLD; Familial partial lipodystrophy, PCSK9; Proprotein convertase subtilisin/kexin type 9

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ISSN: 1476-511X

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