Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population, pragmatic trial on patients with recent
myocardial infarctions 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, nonfatal
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 with 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 every 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 Long-Term Intervention with
Pravastatin in Ischaemic Disease (
LIPID) trial, where 5.2 lives could be saved per 1000 hypercholesterolemic,
coronary heart disease patients treated with
pravastatin for 1 yr. The choice 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, and the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of nonfatal
myocardial infarction) all strongly suggest 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 analyses 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.