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Author Notes:

Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115., Email: dlbhattmd@post.harvard.edu

The authors thank the Amarin team members who are not authors of this article but who contributed to the success of the trial and of these analyses, including K. Diffin, A. Granger, and G. Chester, for operational support; R. Bhavanthula, R.H. Iroudyassamy, J. Jin, D. Klevak, G. Liu, H. Panchal, J. Shi, R. Wang, and S.-R. Wang, for data management and statistical support; and K. Keating from Amarin and S. Mercuro from Brigham and Women’s Hospital for editorial assistance (limited to formatting and collation of coauthor comments); and the investigators, the study coordinators, and especially the patients who participated in REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl – Intervention Trial).

See publication for disclosures.


Research Funding:

The study was funded by Amarin Pharma, Inc., which was involved in the study design, collection, analysis, and interpretation of data, and development and review of this article. The decision to submit the article for publication was made by the authors.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cardiac & Cardiovascular Systems
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • eicosapentaenoic acid ethyl ester
  • fatty acids
  • omega-3
  • lipids
  • prevention and control
  • renal insufficiency
  • chronic
  • triglycerides

Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL

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Journal Title:



Volume 144, Number 22


, Pages 1750-1759

Type of Work:

Article | Final Publisher PDF


BACKGROUND: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function. METHODS: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min-1·1.73 m-2 (range, 17-123 mL·min-1·1.73 m-2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59-0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57-0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min-1·1.73 m-2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51-0.95]; P=0.02). Although patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86-2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90-2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76). CONCLUSIONS: In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Copyright information:

© 2021 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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