Patel V, Sohail R, Alam M, Chaudhry S, Mehdi S, Patel S, Patel R, Khattak R, Khan Z, Patel M. Dose-dependent efficacy of olezarsen in high-risk hypertriglyceridemia: A meta-analysis. World J Cardiol 2026; 18(7): 121611 [DOI: 10.4330/wjc.121611]
Corresponding Author of This Article
Vyom Patel, MD, Principal Investigator, Department of Internal Medicine, Indiana University School of Medicine, 8644 Messiah Dr, APT K, Evansville, IN 47591, United States. vyompate@iu.edu
Research Domain of This Article
Cardiac & Cardiovascular Systems
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research-article
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Patel V, Sohail R, Alam M, Chaudhry S, Mehdi S, Patel S, Patel R, Khattak R, Khan Z, Patel M. Dose-dependent efficacy of olezarsen in high-risk hypertriglyceridemia: A meta-analysis. World J Cardiol 2026; 18(7): 121611 [DOI: 10.4330/wjc.121611]
Vyom Patel, Zaraq Khan, Department of Internal Medicine, Indiana University School of Medicine, Evansville, IN 47591, United States
Rohab Sohail, Madihah Alam, Shahryar Chaudhry, Samar Mehdi, Simran Patel, Rohan Patel, Ridda Khattak, Department of Internal Medicine, Bayhealth Medical Center, Dover, DE 19901, United States
Manan Patel, Department of Biological Science, University of Illinois at Chicago, Chicago, IL 60607, United States
Author contributions: Patel V was responsible for conceptualization, methodology, data curation, writing - original draft, supervision; Sohail R was responsible for data curation, formal analysis, writing - review & editing Alam M, Chaudhry S, Mehdi S, Patel S, and Patel R were responsible for writing - original draft; Khattak R was responsible for study screening, writing - original draft; Khan Z was responsible for methodology, validitation, writing - review and editing; and Patel M was responsible for visualization, writing - original draft.
AI contribution statement: The use of AI tools (ChatGPT and Claude) was used exclusively to enhance language quality and formatting assistance of manuscript and response to reviewers. Furthermore, the involvement of AI tools was not part of any other aspect of this research, such as designing, analyzing data, and interpreting the findings. It is also declared that there are no images or tables created using AI in this manuscript.
Conflict-of-interest statement: An abstract was previously presented at American College of Cardiology in March 2026 and published in the conference supplement. The authors have no competing interests to disclose related to the content of this manuscript. All authors declare that they have no relationship with industry and other relevant entities-financial or otherwise-within the past 2 years that could be construed as a potential conflict of interest. No external funding was received for this study, and the research was conducted independently of industry involvement.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Vyom Patel, MD, Principal Investigator, Department of Internal Medicine, Indiana University School of Medicine, 8644 Messiah Dr, APT K, Evansville, IN 47591, United States. vyompate@iu.edu
Received: March 30, 2026 Revised: May 2, 2026 Accepted: June 16, 2026 Published online: July 26, 2026 Processing time: 111 Days and 19.9 Hours
Abstract
BACKGROUND
Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (apoC-III), has shown promise in reducing triglyceride (TG) levels in patients with high-risk hypertriglyceridemia. This meta-analysis evaluates the comparative efficacy of different dosing regimens.
AIM
To compare the efficacy and safety of olezarsen 80 mg vs 50 mg in patients with high-risk hypertriglyceridemia through a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
PubMed, the Cochrane Library, and Google Scholar were searched for RCTs comparing olezarsen 80 mg to 50 mg. Three studies were analyzed using RevMan 5.4.1 random-effects models to obtain mean difference (MD) with 95%CIs.
RESULTS
Olezarsen 80 mg showed statistically significant reduction in apoC-III (MD = -0.26; 95%CI: -0.51 to - 0.01; P = 0.04). Whereas no difference was seen in TG levels (MD = -0.72; 95%CI: -1.55 to 0.12; P = 0.09), low density lipoproteins (MD = -0.03; 95%CI: -0.16 to 0.10, P = 0.67), very low-density lipoproteins (MD = -0.09; 95%CI: -0.22 to 0.04; P = 0.18), non-high-density lipoproteins (HDL; MD = -0.16; 95%CI: -0.50 to 0.18, P = 0.35), HDL (MD = 0.05; 95%CI: -0.08 to 0.18; P = 0.44), apolipoprotein B (MD = -0.91; 95%CI: -2.70 to 0.88; P = 0.32), adverse effects [AEs; relative risk (RR) = 1.04; 95%CI: 0.96-1.11; P = 0.35], serious AE (RR = 1.40; 95%CI: 0.97-2.02; P = 0.07), hypersensitivity reaction (RR = 1.71; 95%CI: 0.51-5.75; P = 0.39), renal dysfunction (RR = 1.13; 95%CI: 0.62-2.04; P = 0.69), hepatic dysfunction (RR = 1.07, 95%CI: 0.55-2.09; P = 0.84) or thrombocytopenia (RR = 1.57; 95%CI: 0.28-8.75; P = 0.61).
CONCLUSION
Apart from a limited dose-dependent effect on apoC-III, higher dose is not associated with any definitive advantage or disadvantage, highlighting a need for further research.
Core Tip: This meta-analysis of three randomized controlled trials is the first to directly compare olezarsen 80 mg vs 50 mg in patients with high-risk hypertriglyceridemia. While the 80 mg dose produced a statistically significant incremental reduction in apolipoprotein C-III (apoC-III), no significant differences were observed in triglyceride, non-high-density lipoprotein cholesterol, or safety outcomes. These findings suggest that higher dosing confers limited added benefit beyond apoC-III suppression, though equivalence cannot be established from the available evidence.
