CORRESPONDENCE: LETTER TO THE EDITOR
The Role of Omega-3 Fatty Acids in Primary Prevention of Coronary Artery Disease and in Atrial Fibrillation Is Controversial
Palaniappan Saravanan, MD* and
Neil C. Davidson, MD
* Cardiovascular Research Group, University of Manchester, 46. Grafton Street, Manchester M13 9LT, United Kingdom (Email: palaniappan.saravanan{at}manchester.ac.uk).
We read with interest a recent review article on the cardiovascular effects of omega-3 fatty acids ( -3 PUFA) by Lavie et al. (1) and wish to highlight some of the controversial issues in this review. In relation to the role of -3 PUFA in primary prevention of coronary artery disease (CAD), the authors quote 3 studies—the DART (Diet And Reinfarction Trial) (2), GISSI Prevenzione (Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico–Prevenzione) study (3), and JELIS (Japan EPA Lipid Intervention Study) (4)—as supportive evidence for a beneficial effect. As discussed further in the same review, the DART and GISSI Prevenzione studies are secondary prevention studies, and in the JELIS—which included 14,981 subjects in primary prevention and 3,664 subjects in secondary prevention—major coronary events were indeed significantly reduced in the -3 PUFA-treated subjects. However, when the groups with and without previous CAD (i.e., primary and secondary prevention cohorts) were individually analyzed, there was no benefit in the primary prevention group. Therefore, the 3 studies quoted by the authors do not lend any supportive evidence to the claim that -3 PUFA are useful in primary prevention of CAD.
In addition, the authors claim that the most significant antiarrhythmic effects of -3 PUFA are noted in studies on atrial fibrillation (AF) and quote 2 interventional studies (5,6) in addition to 1 observational study (7). To our knowledge, there has been only 1 interventional study published on the effect of -3 PUFA on AF after coronary artery bypass graft surgery. This study by Calò et al. (5) is a relatively small open-label study in 160 patients who received 2 g/day of -3 PUFA for 5 days before coronary artery bypass surgery. The second study referred to by the authors (6) is in fact a systematic review of studies that have evaluated all interventions that might be of benefit in reducing AF after coronary artery bypass graft surgery.
We wish to highlight that there were 2 large epidemiological studies—the Rotterdam Study (8) quoted by the authors and the Danish Diet, Cancer and Health study (9)—that showed no association between the risk of developing AF and dietary fish intake.
Of note, the study by Mozaffarian et al. (7) exclusively looked at subjects  65 years of age and could not be extrapolated to the entire population at risk of AF, which would include both young (often lone AF) and old (often with underlying structural heart disease).
The authors have failed to indicate that a recent systematic review by León et al. (10) and a systematic review of the 3 large studies on implantable cardioverter-defibrillator population (11) have reported no benefit with -3 PUFA therapy on cardiac arrhythmias. Hence, we believe that the role of -3 PUFA on primary prevention of CAD and AF are far from clear as this review seems to suggest.
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References
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1. Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases J Am Coll Cardiol 2009;54:585-594.[Abstract/Free Full Text]2. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet And Reinfarction Trial (DART) Lancet 1989;2:757-761.[Web of Science][Medline] 3. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI Prevenzione trial Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico Lancet 1999;354:447-455.[CrossRef][Web of Science][Medline] 4. Yokoyama M, Origasa H, Matsuzaki M, et al. Japan EPA lipid intervention study (JELIS) Investigators Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis Lancet 2007;369:1090-1098.[CrossRef][Web of Science][Medline] 5. Calò L, Bianconi L, Colivicchi F, et al. N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial J Am Coll Cardiol 2005;45:1723-1728.[Abstract/Free Full Text] 6. Crystal E, Garfinkle MS, Conolly SS, Ginger TT, Sleik K, Yusuf SS. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery Cochrane Database Syst Rev 2004;4CD003611. 7. Mozaffarian D, Psaty BM, Rimm EB, et al. Fish intake and risk of incident atrial fibrillation Circulation 2004;110:368-373.[Abstract/Free Full Text] 8. Brouwer IA, Heeringa J, Geleijnse JM, Zock PL, Witteman JC. Intake of very long-chain n-3 fatty acids from fish and incidence of atrial fibrillation. The Rotterdam Study. Am Heart J 2006;151:857-862.[CrossRef][Web of Science][Medline] 9. Frost L, Vestergaard P. n-3 fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study Am J Clin Nutr 2005;81:504. 10. León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT. Effect of fish oil on arrhythmias and mortality: systematic review BMJ 2008;337:a2931.[Abstract/Free Full Text] 11. Brouwer IA, Raitt MH, Dullemeijer C, et al. Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators Eur Heart J 2009;30:8206.
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References