The Mechanism of Action of Omega-3 Fatty Acids in Secondary Prevention Post-Myocardial Infarction

Nigel Harrison; Brihad Abhyankar

Disclosures

Curr Med Res Opin. 2005;21(1):95-100. 

In This Article

A Brief Overview of the Trials Showing CHD-Related Benefits of Omega-3 Fatty Acids

The Zutphen study[3] showed that men who rarely or never ate fish had a significantly higher rate of coronary artery disease than those who ate fish more than once a week. Further supportive evidence, strongly suggesting a protective effect of omega-3 fatty acids, comes from the Multiple Risk Factor Intervention Trial[4] the Honolulu Heart Programme[5] and the Western Electric Study.[6] The Lyon Diet Heart trial[7] compared a Mediterranean diet rich in omega-3 fatty acids and alpha-linolenic acids (LNA) with the American Heart Association step 1 diet in patients with known MI. No improvement in the lipid profile, lipoproteins or body mass index was seen, yet there was a striking difference in mortality, with 59 events in the control group and 14 events in the study group showing a reduction of 76% (<0.0001).

The Diet and Re-infarction Trial[8] (DART) demonstrated a 29% ( p < 0.05) all-cause mortality reduction over two years in men who ate fish or consumed fish oils and who had a previous history of MI. While the rate of non-fatal MI was unchanged and no significant cholesterol lowering was observed, this study sparked interest in whether a diet rich in fish oil could reduce the risk of sudden death. The observed striking difference in early mortality in the trial suggested a possible antiarrhythmic or antithrombotic potential rather than an influence on atherosclerosis, which would cause events to occur later.

Siscovick and colleagues[9] showed in a population-based, case-controlled study that patients consuming modest amounts of fish - the equivalent of one fatty fish meal per week - had a lower risk of primary cardiac arrest, compared with those who did not eat any fish at all.

Women in the large ( p = 84 129) Nurses Health Study,[10] who consumed higher amounts of fish and omega-3 fatty acids, had a lower risk of CHD, particularly IHD deaths over a 16-year follow-up period. In 2002 Albert et al.[11] proposed that the long-chain omega-3 fatty acids found in fish may reduce the risk of sudden death from cardiovascular causes among apparently healthy men, without previous history of cardiac disease. This led to a prospective, nested case control analysis among healthy men followed up for up to 17 years in the US Physicians Health Study.[12] The results showed that baseline blood levels of long chain omega-3 fatty acids were inversely related to the risk of sudden death. The data suggest that eating more fish or taking omega-3 fatty acid supplements may represent a low cost, low risk intervention to reduce the risk of sudden death in the population.

The results of the GISSI-Prevenzione study,[2] originally published in 1999, were also presented as a rapid access online publication in 'Circulation' in 2002.[13] This latter report included a re-analysis of the time course of the results of the original GISSI-Prevenzione trial. It was demonstrated that post-MI patients treated with a highly purified supplement of the omega-3 fatty acids EPA and DHA had a significant reduction in the combined primary end points of: (A) death, non-fatal MI and non-fatal stroke, and, (B) cardiovascular death, non-fatal MI and non-fatal stroke. Secondary end points in the study included cardiovascular mortality (cardiac death, coronary death and sudden death), other deaths and non-fatal cardiovascular events.

The GISSI-Prevenzione trial[2] enrolled 11 323 patients with recent MI (< three months; median 16 days) in a multi-centre, open-label, parallel, clinical trial with a follow-up of 3.5 years. The four arms of the study evaluated the efficacy of the 1 g omega-3 fatty acid supplement, vitamin E 300 mg/day, a combination of the two and a control. All patients, regardless of their allocation, received the same care strategies, including lifestyle modification and up-to-date secondary preven-tion measures.

Long-term follow-up data showed that the early administration of omega-3 fatty acids in the dose of 1 g/day (one Omacor capsule), in addition to proven secondary prevention measures, reduced the risk of sudden death by up to 45% and overall mortality by 20% at 42 months.

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