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Cited by 214Lipid metabolism and disordersLipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and Lipoproteins

The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk

Bergmark, Brian A., Marston, Nicholas A., Prohaska, Thomas A., Alexander, Veronica J., Zimerman, André, Moura, Filipe A., Murphy, Sabina A., Goodrich, Erica L., Zhang, Shuanglu, Gaudet, Daniel, Karwatowska-Prokopczuk, Ewa, Tsimikas, Sotirios, Giugliano, Robert P., Sabatine, Marc S.·2024·New England Journal of Medicine
DOI 10.1056/nejmoa2402309
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Abstract

BACKGROUND: Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering. METHODS: In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. RESULTS: A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups. CONCLUSIONS: In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.).

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Crossref · 10.1056/nejmoa2402309

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Metadata

Authors
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., Karwatowska-Prokopczuk, E., Tsimikas, S., Giugliano, R. P., & Sabatine, M. S.
Affiliations
  • Brigham and Women's Hospital (US)
  • From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston (B.A.B., N.A.M., A.Z., F.A.M., S.A.M., E.L.G., S.Z., R.P.G., M.S.S.); Ionis Pharmaceuticals, Carlsbad (T.A.P., V.J.A., E.K.-P., S.T.), and the Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla (S.T.) — both in California; and the Department of Medicine, Université de Montréal and Ecogene-21 Clinical Research Centre, Quebec, QC, Canada (D.G.).
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2024-05-16
Volume
390
Issue
19
Pages
1770-1780
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2402309
OpenAlex
W4394063777
Semantic Scholar
e9297203e04305826d00d4054d21576bb119360c
Cited by
214
References
28
Citations by year
2026: 71 · 2025: 98 · 2024: 45
FWCI
60.15
Type
journal article
Language
en
Open access
closed
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ionis Pharmaceuticals
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
olezarsen, hypertriglyceridemia, antisense oligonucleotides, apolipoprotein C-III, triglyceride lowering, cardiovascular risk, apolipoprotein B, non-HDL cholesterol, LDL cholesterol, triglyceride-rich lipoproteins, dose comparison, adverse events, hepatic safety, renal safety, platelet abnormalities
MeSH terms
Heart Disease Risk Factors, Adult, Aged, Hypolipidemic Agents, Apolipoproteins B, Cardiovascular Diseases, Double-Blind Method, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Oligonucleotides, Triglycerides, Hypertriglyceridemia, Oligonucleotides, Antisense, Apolipoprotein C-III

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