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#69 Omega-3 Fatty Acids (Fish Oil) for Patients with Cardiovascular Disease (CVD)

Do omega-3 fatty acid supplements reduce the risk of cardiovascular events in patients with and without existing cardiovascular disease (CVD)?

Evidence does not support using omega-3 fatty acid supplements for primary or secondary prevention of CVD.

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One meta-analysis1 and two subsequent Randomized Controlled Trials (RCTs)2,3 evaluated omega-3s for primary or secondary CVD prevention. 
  • Meta-analysis1 of 20 RCTs (68,680 patients) 
    • Two RCTs administering dietary omega-3s showed opposing effects on all-cause mortality. 
  • Eighteen RCTs administering omega-3 supplements found: 
    • No significant difference in all-cause mortality, myocardial infarction or stroke. 
    • Note: 9% relative reduction in cardiac death not significant after adjusting for multiple comparisons, and not reflected in change in above outcomes or sudden death. 
  • RCT2 of 12,513 patients at high CVD risk showed no difference at five years in: 
    • Death or hospitalization from cardiovascular cause: Omega-3s 11.7% versus 11.9% with placebo. 
    • Other CVD outcomes unchanged. 
  • Secondary outcomes of AREDS2 RCT3 of 4,203 patients with age-related macular degeneration: 
    • No difference at 4.8 years in CVD morbidity or mortality: 9% in both groups. 
  • Only RCT4 in patients with heart failure (included in above systematic review) demonstrated: 
    • Decreased all-cause mortality: Omega-3s 27.3% versus placebo 29.1%. 
    • But achieved statistical significance (p=0.041) only after adjusting for differences in baseline characteristics.
  • Omega-3s are a group of polyunsaturated fatty acids found in fish oils, flax seed (to a lesser extent other nuts), canola oil, and soybeans. 
  • Observed lower CVD in the Inuit was thought to be due to their high marine omega-3 intake.5 
  • The only RCTs to demonstrate CVD benefits of omega-3s were not blinded6,7 or had low use of standard cardiovascular medications (like statins).6 
  • Meta-analyses of lower-level evidence (cohort studies) show inconsistent effects of omega-3s on outcomes.8-10 
  • Canada’s Food Guide11 and the American Heart Association12 encourage consumption of two or more portions of fish per week for primary and secondary prevention of CVD. 
    • Since 2013, NICE guidelines no longer recommends eating fish specifically for CVD prevention as no benefit (though acknowledge no evidence of harm in doing so).13 
updated by ricky July 23 2016

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  • Fred Janke MD MSc CCFP
  • Michael R. Kolber BSc MD MSc CCFP
  • Ricky D. Turgeon BSc(Pharm) ACPR PharmD

1. Rizos EC, Ntzani EE, Bika E, et al. JAMA. 2012; 308:1024-33.

2. The Risk and Prevention Study Collaborative Group. N Engl J Med. 2013; 368:1800-8.

3. Writing Group for the AREDS2 Research Group. JAMA Intern Med. 2014; 174:763-71.

4. GISSI-HF Investigators. Lancet. 2008; 372:1223-30.

5. Stone NJ. Circulation. 1996; 94:2337-40.

6. GISSI-Prevenzione Investigators. Lancet. 1999; 354:447-55.

7. Yokoyama M, Origasa H, Matsuzaki M, et al. Lancet. 2007; 369:1090-8.

8. Hooper L, Thompson RL, Harrison RA, et al. Cochrane Database Syst Rev. 2004; (4):CD003177.

9. Leung SSL, Stark KD, Thanassoulis G, et al. Am J Med. 2014; 127:848-57.

10. Del Gobbo LC, Imamura F, Aslibekyan S, et al. JAMA Intern Med. 2016; 176(8):1155-66.

11. Canada’s Food Guide. Available for download at: Last Accessed: July 24, 2016.

12. Kris-Etherton PM, Harris WS, Appel LJ, et al. Circulation. 2002; 106:2747-57.

13. NICE Guidelines. Available for download at: Last Accessed: July 24, 2016.

Authors do not have any conflicts of interest to declare.

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