Optimizing cardiovascular health: a systematic review and meta-analysis of olezarsen dosages in high-risk hypertriglyceridemic patients
Abstract
Background Hypertriglyceridemia and hypercholesterolemia are well-known risk factors for atherosclerotic cardiovascular disease (ASCVD), especially in patients already at elevated cardiovascular risk. Despite current treatment approaches, including lifestyle changes and medication, many individuals do not reach ideal lipid levels, emphasizing the need for new therapeutic options. Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (ApoC-III) synthesis, has emerged as a promising candidate to reduce residual cardiovascular risk in these patients. Aim This systematic review and meta-analysis aimed to assess the effectiveness and safety of different dosages of Olezarsen in patients with high-risk hypertriglyceridemia. Additionally, it explored whether varying dosage regimens impacted lipid outcomes and adverse events. Methods Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published in English. The studies included compared different doses of Olezarsen with placebo in high-risk hypertriglyceridemia patients. Primary outcomes were changes in triglycerides (TG), very-low-density lipoprotein cholesterol (VLDL-C), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and treatment-emergent adverse events (TEAE). Secondary outcomes included changes in non-HDL-C and total cholesterol (TC). The…
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Prior systematic reviews and meta-analyses of olezarsen in hypertriglyceridemic or dyslipidemic cohorts were limited by small sample sizes, underpowered individual endpoints, lack of restriction to severe hypertriglyceridemia, and absence of systematic evaluation of pancreatitis as a clinical outcome.
“Prior systematic reviews and meta-analyses have reported the efficacy of olezarsen in hypertriglyceridemic or dyslipidemic cohorts; however, these studies were limited by small sample sizes, underpowered individual endpoints, lack of restriction to SHTG, and the absence of systematic evaluation of pancreatitis as a clinical outcome [10][11][12][13].”
From Efficacy of Olezarsen in Severe Hypertriglyceridemia and Acute Pancreatitis Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [11]
Cites
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · BMJ · doi:10.1136/bmj.n71 · Cited by 108,283 · see citing works
Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019
Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M., Barengo, N. C., Beaton, A. Z., Benjamin, E. J., Benziger, C. P., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.11.010 · Cited by 11,449 · see citing works
A Modern Approach to Dyslipidemia
Berberich, A. J., & Hegele, R. A. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab037 · Cited by 503 · see citing works
Wadhera, R. K., Steen, D. L., Khan, I., Giugliano, R. P., & Foody, J. M. (2016) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2015.11.010 · Cited by 306 · see citing works
Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome
Stroes, E. S. G., Alexander, V. J., Karwatowska-Prokopczuk, E., Hegele, R. A., Arca, M., Ballantyne, C. M., Soran, H., Prohaska, T. A., Xia, S., Ginsberg, H. N., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2400201 · Cited by 271 · cited 3× · see citing works
“Olezarsen has also been shown to significantly lower triglyceride levels in adult patients diagnosed with familial chylomicronemia syndrome, a rare genetic disorder characterized by severe hypertriglyceridemia (Stroes et al. 2024).”
Hypertriglyceridemia and atherosclerosis
Peng, J., Luo, F., Ruan, G., Peng, R., & Li, X. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0625-0 · Cited by 262 · see citing works
Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk
Bergmark, B. A., Marston, N. A., Prohaska, T. A., Alexander, V. J., Zimerman, A., Moura, F. A., Murphy, S. A., Goodrich, E. L., Zhang, S., Gaudet, D., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2402309 · Cited by 198 · see citing works
Makover, M. E., Shapiro, M. D., & Toth, P. P. (2022) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2022.100371 · Cited by 133 · see citing works
Hypertriglyceridemia: A Neglected Risk Factor for Ischemic Stroke?
Liang, H., Zhang, Q., Hu, Y., Liu, G., & Qi, R. (2022) · Journal of Stroke · doi:10.5853/jos.2021.02831 · Cited by 62 · see citing works
Karwatowska‐Prokopczuk, E., Tardif, J., Gaudet, D., Ballantyne, C. M., Shapiro, M. D., Moriarty, P. M., Baum, S. J., Amour, E. S., Alexander, V. J., Xia, S., et al. (2022) · Journal of clinical lipidology · doi:10.1016/j.jacl.2022.06.005 · Cited by 51 · see citing works
Karwatowska‐Prokopczuk, E., Lesogor, A., Yan, J., Hoenlinger, A., Margolskee, A., Li, L., & Tsimikas, S. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02297-5 · Cited by 19 · see citing works
Pan, B.-Y., Chen, C.-S., Chen, F.-Y., & Shen, M.-Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312759 · Cited by 19 · see citing works
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Björnson, E., Adiels, M., Taskinen, M., Packard, C. J., & Borén, J. (2026) · Current Atherosclerosis Reports · doi:10.1007/s11883-026-01399-y · Cited by 7 · see citing works
Rehman, A., Rajdeep, D., Mohnkern, J. D., & Lin, J. (2026) · Digestive Diseases and Sciences · doi:10.1007/s10620-026-09846-1 · Cited by 2 · see citing works
Coan, A. C. C., Katsuyama, E. S., Lopes, R. A., Sanchez, C. V., Prata, A. A., Fukunaga, C. K., Talavera, A., & Shapiro, M. D. (2026) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2026.105022
- Authors
- Serag, I., Alkhawaldeh, I. M., Shati, A. A., Alqahtani, Y. A., Alattar, A., Khader Alkhamaiseh, S. A., & Moawad, M. H. E. D.
- Affiliations
- Mansoura University (EG)
- Mutah University (JO)
- King Khalid University (SA)
- Suez Canal University (EG)
- Corresponding author
- Serag, Ibrahim
- ORCID
- Venue
- Naunyn-Schmiedeberg's Archives of Pharmacology
- Published
- 2025-07-14
- Volume
- 399
- Issue
- 1
- Pages
- 645-664
- ISSN
- 0028-1298 (ISSN-L)
- 1432-1912
- OpenAlex
- W4412391430
- Cited by
- 3
- References
- 12
- Citations by year
- 2026: 3
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Naunyn-Schmiedeberg s Archives of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- olezarsen, hypertriglyceridemia, apolipoprotein C-III, antisense oligonucleotides, dose-response relationship, triglycerides, VLDL cholesterol, apolipoprotein B, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, residual cardiovascular risk, atherosclerotic cardiovascular disease, lipid-lowering therapy, adverse events, drug safety
- MeSH terms
- Heart Disease Risk Factors, Cardiovascular Diseases, Dose-Response Relationship, Drug, Humans, Triglycerides, Hypertriglyceridemia, Randomized Controlled Trials as Topic, Oligonucleotides, Antisense, Apolipoprotein C-III
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