Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin Eafter myocardial infarction: results of the GISSI-Prevenzione trial

Background There is conflicting evidence on the benefits of foods rich in v itamin E (alpha-tocopherol), n-3 polyunsaturated fatty acids (PUFA), and th eir pharmacological substitutes. We investigated the effects of these subst ances as supplements in patients who had myocardial infarction. Methods From October, 1993, to September, 1995, 11324 patients surviving re cent (less than or equal to 3 months) myocardial infarction were randomly a ssigned supplements of n-3 PUFA (Ig daily, n=2836), vitamin E (300 mg daily , n=2830), both (n=2830), or none (control, n=2828) for 3.5 years. The prim ary combined efficacy endpoint was death, non-fatal myocardial infarction, and stroke. Intention-to-treat analyses were done according to a factorial design (two-way) and by treatment group (four-way). Findings Treatment with n-3 PUFA, but not vitamin E, significantly lowered the risk of the primary endpoint (relative risk decrease 10% [95% CI 1-18] by two-way analysis, 15% [2-26] by four-way analysis). Benefit was attribut able to a decrease in the risk of death (14% [3-24] two-way, 20% [6-33] fou r-way) and cardiovascular death (17% [3-29] two-way, 30% [13-44] four-way). The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint (14% [1-26]) and for fatal events (20% [5-33]). Interpretation Dietary supplementation with n-3 PUFA led to a clinically im portant and satistically significant benefit. Vitamin E had no benefit. Its effects on fatal cardiovascular events require further exploration.