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n-3 fatty acids in the secondary prevention of coronary heart disease

An article from the e-journal of the ESC Council for Cardiology Practice

Epidemiological studies, animal and in-vitro experiments, and the beneficial effects on coronary risk factors have given rise to the hypothesis that n-3 polyunsaturated fatty acids (PUFA) from fish may be protective in patients suffering from coronary heart disease (CHD) (1).

Chronic Ischaemic Heart Disease (IHD)

Burr et al. (2) randomised 2.000 men with a recent myocardial infarction (MI) to various dietary changes, including an increased intake of n-3 PUFA (fatty fish twice weekly or alternatively fish oil capsules) for two years (the DART trial). There was a significant 29% reduction in total mortality and in deaths from CHD, and a non-significant increase in non-fatal MI in the group given fish advice. The authors suggested an anti-arrhythmic effect of n-3 PUFA as an explanation for their findings. A 10-year follow-up study showed that the effect of the initial dietary changes in DART did not translate into a sustained survival benefit (3).

In the Lyon study, the effect of a Mediterranean type of diet with an increased intake of fish, bread, fruit, vegetables and in particular the non-marine n-3 PUFA, a-linolenic acid, was investigated in 600 patients with a recent MI (4). There was a 70% reduction in cardiac morbidity and mortality in the patients randomised to the Mediterranean diet. However, in this trial an increased intake of fish was only one of several dietary changes.

The Itallian, multicenter GISSI-Prevenzione trial was initiated in 1993 and published in 1999 (5). 11,324 patients with a recent (< 3 months) MI were randomised to one of four groups in an open-label 2x2 factorial design. One group received one daily capsule of 1 g of fish oil containing approximately 0.85 g of n-3 PUFA as ethyl esters; a second group received one capsule of vitamin E 300 mg per day; a third group received the combination of n-3 and vitamin E while the last group received no supplements. The supplements were given in addition to standard treatment of patients with a recent MI. The patients were followed for 3.5 years, and the primary endpoints were the cumulative rate of 1) total death, non-fatal MI and non-fatal stroke or 2) cardiovascular death, non-fatal MI and non-fatal stroke. In a four-way, intention to treat analysis, there was a significant relative reduction of 15% in the first primary endpoint (all-cause death + non-fatal MI + non-fatal stroke), and a significant 20% reduction in the other primary endpoint (cardiovascular death + non-fatal MI + non-fatal stroke) in patients randomised to n-3 PUFA. The reduction in fatal events was entirely due to a 30% reduction in cardiovascular deaths.

In a recent publication comprising 3,114 men below 70 years of age with angina pectoris by the investigators of the DART study and performed with a similar design - patients advised to eat fatty fish twice a week (6). Surprisingly, total mortality was increased by 15% (p=0.13), coronary deaths increased by 26% (p=0.047) and SCD increased by 54% (p=0.025) in the fish group. The authors offered several explanations for their unexpected findings, the most likely probably being results by chance or by changes in diet or lifestyle in the n-3 group. Anyway, the study raises questions about the use of n-3 PUFA in patients with stable angina pectoris.

In a Norwegian study 610 patients undergoing coronary artery bypass surgery were supplemented with 3.5 g n-3 PUFA daily as fish oil capsules or no supplement for one year. Graft patency for venous grafts was significantly better after one year of follow-up in those randomised to fish oil (7). The effect of n-3 PUFA on re-stenosis rate after PTCA was initially reported to be promising. However, larger trials set up to finally prove an effect of n-3 PUFA on re-stenosis rate failed to do so. These trials were performed before coronary stents were used routinely.

The potential anti-arrhythmic effect of n-3 PUFA is believed to be important (8,9,10), and is currently investigated in studies both in patients at increased risk for sudden cardiac death and in patients treated with an implantable cardioverter device (ICD),

In our opinion, patients with recent MI should eat fatty fish at least twice weekly aiming for an intake of 7 g of n-3 fatty acids per week. Despite the negative outcome of the DART/angina pectoris trial we tend to expand this recommendation to patients with CHD. Another controversial question is whether patients with CHD not consuming fish should be given fish oil concentrates. We would recommend 1 g of n-3 fatty acids from high quality products daily to such patients. However, more studies are warranted in different groups of heart patients to further clarify the issue.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.


1. Schmidt EB. n-3 fatty acids and the risk of coronary heart disease. Dan Med Bull 1997; 44: 1-22.

2. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, and Deadman NM. Effects of changes in fat, fish, and fibre intakes on death and reinfarction: diet and reinfarction trial (DART). Lancet 1989; 2: 757-61.

3. Burr ML, Sweetnam PM, Fehily AM. Diet and reinfarction. Eur Heart J 1994; 15: 1152-3.

4. De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin J, Monjaud I, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994; 343: 1454-9.

5. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999; 354: 447-55.

6. Ness AR, Hughes J, Elwood PC, Whitley E, Smith GD, Burr ML. The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction Trial. Eur J Clin Nutr 2002; 56: 512-8.

7. Eritsland J, Arnesen H, Grønseth K, Fjeld NB, Abdelnoor M. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol 1996; 77: 31-6.

8. Marchioli R, Barzi F, Bomba E, Chieffo C, Gregorio DD, Mascio RD, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GN, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, and Valgussa F. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction. Circulation 2002; 105: 1897-903.

9. Christensen JH. n-3 fatty acids and the risk of sudden cardiac death: Emphasis on heart rate variability (thesis). Dan Med Bull 2003; 50: 347-67.

10. De Caterina R, Madonna R, Zucchi R, La Rovere MT. Antiarrhythmic effects of omega-3 fatty acids: From epidemiology to bedside. Am Heart J 2003; 146: 420-30.


Vol3 N°01

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.