Treatment with n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-prevenzione trial

GISSI-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarction conducted in the framework of the Italian public health system. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA 1 g daily, but not vitamin E 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. At variance from the orientation of a scientific scenario largely dominated by the ‘cholesterol-heart hypothesis’, GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. As to the relevance and comparability of GISSI-Prevenzione results, up to 5·7 lives could be saved per 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the LIPID trial, where 5·2 lives could be saved per 1000 hypercholaesterolemic, CHD patients treated with pravastatin for 1 year. The choice in favour of a relatively low-dose regimen (1 g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of non-fatal myocardial infarction), all suggest that it can confidently be said that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the preliminary analyses (to be submitted in the final form for publication) of the interplay between diet and n-3 PUFA: there is an interesting direct correlation between size of the effect and ‘correctness’ of background diets. It can be anticipated that a conceptual barrier must be overcome: a ‘dietary drug’ should be added to ‘dietary advice’, which remains fundamental to allow this statement to become true in clinical practice.