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#277 Somethin’ Fishy: Prescription variants of Omega-3 to prevent cardiovascular disease 

Do prescription variants of omega-3’s, like icosapent, reduce the risk of cardiovascular events when added to statins?

In high risk patients, icosapent reduced cardiovascular events to 17% from 22% on placebo after 5 years. In lower risk patients, Eicosapentaenoic Acid (EPA) ethyl ester reduced major cardiovascular events to 2.8% from 3.5% with control after 5 years. Whether these products differ from each other or traditional omega-3 fatty acids (that don’t show cardiovascular benefit) is unknown. Cost will likely limit use.  

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Focusing on patient-oriented outcomes from large randomized controlled trials (RCTs) where prescription EPA products were added to statins. 
  • Icosapent: 
    • REDUCE-IT:18179 patients (70% secondary prevention), randomized to icosapent 2g twice daily or placebo. Mean age 64 years, 72% male. After ~5 years: 
      • Composite of cardiovascular events: 17.2% versus 22.0% placebo. Number needed to treat (NNT)=21. 
      • All-cause mortality: 6.7%, versus 7.6% placebo; no difference. 
      • Atrial fibrillation: 5.3% versus 3.9% placebo; number needed to harm (NNH)=71. 
    • EPA ethyl ester: 
      • JELIS:218,645 Japanese (~80% primary prevention) patients with total cholesterol >6.5mmmol/L, randomized (open label) to EPA ethyl ester 1.8 g/day plus statin or statin alone. Mean age 61, 69% female. After ~5 years: 
        • Major coronary events: 2.8% EPA versus 3.5% (NNT=143). 
        • All-cause mortality: no difference. 
        • Adverse events leading to discontinuation: 11.7% EPA ethyl ester plus statin versus 7.2% statin (NNH=23). 
  • Traditional Omega-3’s are made up of EPA and decosahexaenoic acid (DHA). 
    • Icosapent is an ethyl form of EPA,1 a type of long chain omega-3 fatty acid.3 
    • Systematic reviews of omega-3's do not generally find benefit in the prevention of cardiovascular disease4,5 particularly when examining high quality studies.5 
  • Evidence gaps include: 
    • A small secondary prevention trial has not been published.6 
    • Additional trials evaluating EPA on cardiovascular outcomes are not being conducted.7 
    • No studies compare EPA products. 
    • Concerns exist with approving medications on single trial results.8 
  • Only icosapent is approved in Canada.9 
    • Cost (~$3600/year) requires >40% reduction to approach cost effectiveness.10 

James Lanz-O'Brien April 24, 2021

I have a few patients whose primary problem is hypertriglyceridemia. I have traditionally managed them with atorvastatin due to its supposedly superior effect on triglycerides compared to other statins. It is great to have something more evidence based to provide though. Hopefully we will see the cost of icosapent come down to reality soon!

Gilbert Bretecher May 10, 2023

Omega -3 agents have limited effect and are costly

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  • Allison Paige MD CCFP
  • Joey Ton PharmD
  • Michael R Kolber MD CCFP MSc

1. Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2019; 380(1):11-22.

2. Yokoyama M, Origasa H, Matsuzaki M, et al. Lancet. 2007; 369(9567):1090-8.

3. Brinton EA, Mason RP. Lipids Health Dis. 2017; 16:23.

4. Aung T, Halsey J, Kromhout D, et al. JAMA Cardiol. 2018; 3:225-34.

5. Abdelhamid AS, Brown TJ, Brainard JS, et al. Cochrane Database Syst Rev. 2020; 3(2):CD003177.

6. NIH. U.S. National Library of Medicine. Trial # NCT03192579. Available at Accessed Oct 30, 2020.

7. NIH. U.S. National Library of Medicine. Available at Accessed Oct 30, 2020.

8. Haslam A, Prasad V. Circ Cardiovasc Qual Outcomes. 2019;12:e005494.

9. Health Canada Prescription Drug List (PDL): Multiple additions. Available at: Accessed Sept 29, 2020.

10. Canadian Agency for Drugs and Technologies in Health. Available at: Last accessed: Sept 8, 2020.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.