Polyunsaturated Fatty Acids

n-3 polyunsaturated fatty acids (PUFA) have been associated with lower mortality after MI, primarily from a reduction in sudden cardiac death.168 In the GISSI-Prevenzione trial, 3-year treatment with low-dose n-3 PUFA was associated with a significant reduction of total mortality (21%) in patients who survived a recent MI. In the published design paper for the subsequent GISSI-HF trial, the authors described the results of an unpublished, post-hoc analysis of the GISSI-Prevenzione trial, showing that in nearly 2000 post-infarction patients with LV dysfunction enrolled in the trial, the effects of n-3 PUFA on all-cause and sudden mortality were similar to those observed in the overall trial population.169 A single randomized controlled trial, the Italian GISSI-HF trial, has been conducted with n-3 PUFA in the HF population.170 Patients with NYHA Class II-IV symptoms and LVEF <40% were enrolled. Patients with LVEF >=40% were also eligible, provided they had been hospitalized for HF at least once in the preceding year (accounted for 9% of the total population). Patients were randomized to either 1 g/day of PUFA (850-882 mg eicosapentaenoic acid and docosahexaenoic acid as ethyl esters in the average ratio of 1:1.2) or matching placebo. The primary endpoints were time to death, and time to death or cardiovascular hospitalization. A total of 3494 patients were enrolled in the n-3 PUFA group and 3481 in the placebo group. All cause mortality was 27% in the n-3 PUFA group and 29% in the placebo group (adjusted HR 0.91, 95.5% CI 0.833-0.998, P=0.041). All-cause death or cardiovascular hospitalization occurred in 57% of the n-3 PUFA treated patients and 59% of the placebo group (adjusted HR 0.92, 99% CI 0.849-0.999, P=0.009). Patients were receiving standard medical therapy for HF, with 93% on ACE-inhibitors or ARBs, 65% on beta blockers, and approximately 40% on spironolactone. N-3 PUFA was generally well tolerated, with gastrointestinal complaints being the most commonly reported adverse effect in both groups.170 The therapy is not widely adopted, but it may be considered as an adjunctive therapy in patients with chronic HF.