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Heterogeneity in Randomized Controlled Trials of Long Chain (Fish) Omega-3 Fatty Acids in Restenosis, Secondary Prevention and Ventricular Arrhythmias

Clinical Nutrition & Risk Factor Modification Center (D.J.A.J., A.R.J., R.L.T., C.W.C.K.)
Department of Medicine, and Divisions of Endocrinology and Metabolism (D.J.A.J.)
Cardiology (P.D.), St. Michael's Hospital
Departments of Nutritional Sciences (D.J.A.J., A.R.J., R.L.T., C.W.C.K.)
Medicine (D.J.A.J.), Faculty of Medicine, University of Toronto, Toronto
Ontario, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan (C.W.C.K.)
Research Center on Aging, Université de Sherbrooke, Québec (S.C.C.), CANADA
Department of Epidemiology, Statistics and Public Health, Cardiff University, Wales, UNITED KINGDOM (M.L.B.)

Address correspondence to David J.A. Jenkins, Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, 61 Queen St. East, Toronto, Ontario, CANADA, M5C 2T2. E-mail: cyril.kendall{at}utoronto.ca

Randomized controlled trials of marine omega-3 fatty acid supplementation in relation to coronary heart disease (CHD) have inconsistent outcomes, yet public health messages are uniformly positive. Originally, fish were seen as a low saturated fat protein source, and later as a valuable source of omega-3 fatty acids. Early trials indicated that increased fish oil consumption prevented restenosis after coronary angioplasty. Later trials demonstrated that fish oils prolonged life post myocardial infarction (MI). Currently, the potential antiarrhythmic effects of fish derived omega-3 fatty acids are seen as the primary reason for cardiac benefits, as suggested by one trial with compliant subjects with implantable cardioverter defibrillators (ICDs), and sudden death reduction in a post MI trial.

However, the earlier benefits of EPA and DHA on restenosis have only been confirmed in a subgroup in a recent meta-analysis. Newer data indicate that fish oils may increase CHD events in men with angina. Furthermore, in two of three trials in patients with ICDs and a history of ventricular arrhythmias, fish oils showed no significant benefit or even increased the risk of appropriate ICD discharge.

Certain groups of individuals may benefit from long-chain omega-3 fatty acids while others, including men with angina and some individuals with a history of ventricular arrhythmia, may not. Due to significant heterogeneity in the response to fish oils, further studies are required before making widespread recommendations for all groups to increase consumption of fish and fish oil.

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