Preventive use of N-3 fatty acids.

To the Editor: In the editorial “N-3 fatty acids: priority for post–myocardial infarction clinical trials,” Dr Scott Grundy1 (somewhat cautiously) endorsed the need for a trial to test the hypothesis that -3 fatty acid (FA) supplements will reduce risk for coronary death in patients randomized in the immediate post–myocardial infarction period. We support this recommendation, but we differ with Dr Grundy’s assessment of the strength of the evidence for recommending increased intake of eicosapentaenoic and docosahexaenoic acids (EPA and DHA) today. The GISSI Prevenzione study, although not placebo-controlled (blinding -3 FA capsules is not easy), did, however, provide compelling evidence from a randomized trial of 11 000 postinfarction patients that 850 mg of these two FA will reduce total mortality by 28% (P 0.03) and risk for sudden death by 47% (P 0.01).2 This appears to be due to a unique ability of -3 fats to reduce fatal ventricular arrhythmias that are independent of, and additive to, the cardioprotective effects of standard cardiovascular pharmacotherapy (eg, aspirin, angiotensin-converting enzyme inhibitors, statins, and -blockers). These findings are supported by a large and consistent body of evidence correlating fish intake with reduced risk of fatal coronary events.3–5 We disagree with the implication that physicians should refrain from utilizing these FA until further clinical trials are completed (which would delay implementation for many years). Additional large, randomized, placebo-controlled trials using -3 fats to affect clinical end points are needed, but there are multiple population studies supporting the cardioprotective effects of -3 FA, and the randomized trials that have been reported with 0.5 to 3 g of EPA DHA have been uniformly positive. The dearth of large, randomized, placebo-controlled trials is largely due to the pharmaceutical industry’s lack of interest in promoting an agent that cannot be patented. To require the same level of proof as a new drug for a nutritional product designated as “generally recognized as safe” by the Food and Drug Administration with strongly suggestive benefits is in our view excessively conservative. Taking an evidence-based approach, the American Heart Association has endorsed the use of about 1 g of EPA DHA for patients with coronary disease.5 At worst, following this advice is harmless; at best, thousands of lives will be saved.