Effectiveness of icosapent ethyl on first and total cardiovascular events in patients with metabolic syndrome, but without diabetes: REDUCE-IT MetSyn
Open accessAbstract
Aims: Metabolic syndrome (MetSyn) is associated with high risk of cardiovascular (CV) events, irrespective of statin therapy. In the overall REDUCE-IT study of statin-treated patients, icosapent ethyl (IPE) reduced the risk of the primary composite endpoint (CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization) and the key secondary composite endpoint (CV death, non-fatal myocardial infarction, or non-fatal stroke). Methods and results: REDUCE-IT was an international, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled LDL cholesterol and elevated triglycerides to IPE 4 g/day or placebo. The current study evaluated the pre-specified patient subgroup with a history of MetSyn, but without diabetes at baseline. Among patients with MetSyn but without diabetes at baseline (n = 2866), the majority (99.8%) of this subgroup was secondary prevention patients. Icosapent ethyl use was associated with a 29% relative risk reduction for the first occurrence of the primary composite endpoint [hazard ratio: 0.71; 95% confidence interval (CI): 0.59–0.84; P < 0.0001, absolute risk reduction (ARR) = 5.9%; number needed to treat = 17] and a 41% reduction in total (first plus subsequent) events [rate ratio: 0.59; (95% CI: 0.48–0.72); P < 0.0001] compared with placebo. The risk for the key secondary composite endpoint was reduced by 20% (P = 0.05) and a 27% reduction in fatal/non-fatal MI (P = 0.03), 47% reduction in urgent/emergent revascularization (P < 0.0001), and 58% reduction in hospitalization for unstable angina (P < 0.0001). Non-statistically significant reductions were observed in cardiac arrest (44%) and sudden cardiac death (34%). Conclusion: In statin-treated patients with a history of MetSyn, IPE significantly reduced the risk of first and total CV events in REDUCE-IT. The large relative and ARRs observed supports IPE as a potential therapeutic consideration for patients with MetSyn at high CV risk. Registration REDUCE-IT ClinicalTrials.gov number: NCT01492361
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The trends observed in the prespecified REDUCE-IT MetS analysis are consistent with results identified for primary and key secondary composite endpoints.
“Overall, the trends observed in the prespecified REDUCE-IT MetS analysis [7] are consistent with results identified for primary and key secondary composite endpoints.”
From Icosapent ethyl reduces CVD risk in cardiovascular-kidney-metabolic syndrome: REDUCE-IT CKM (2026) · cites this paper as [7]
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- Authors
- Miller, M., Bhatt, D. L., Brinton, E. A., Jacobson, T. A., Steg, P. G., Pineda, A. L., Ketchum, S. B., Doyle, R. T., Tardif, J.-C., & Ballantyne, C. M.
- Affiliations
- Hospital of the University of Pennsylvania (US)
- Icahn School of Medicine at Mount Sinai (US)
- Utah Lipid Center , Salt Lake City, UT , USA
- Emory University (US)
- Université de Paris, FACT (French Alliance for Cardiovascular Trials), Assistance Publique–Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148 , Paris , France
- Amarin (United States) (US)
- Montreal Heart Institute (CA)
- Baylor College of Medicine (US)
- Corresponding author
- Miller, Michael
- ORCID
- Venue
- European Heart Journal Open
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-11
- Volume
- 3
- Issue
- 6
- Pages
- oead114-oead114
- ISSN
- 2752-4191 (ISSN-L)
- PMC
- PMC10684296
- OpenAlex
- W4388637596
- Cited by
- 11
- References
- 32
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 2
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- European Heart Journal Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- Amarin
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- icosapent ethyl, metabolic syndrome, cardiovascular events, REDUCE-IT trial, statin-treated patients, triglycerides, omega-3 fatty acids, myocardial infarction, coronary revascularization, unstable angina, secondary prevention, cardiovascular risk reduction, LDL cholesterol, sudden cardiac death, cardiac arrest
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