In the initial Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto miocardico (GISSI) trial, patients taking n-3 polyunsaturated fatty acids (PUFA) after myocardial infarction had a lower mortality rate than those in the control group. The purpose of the GISSI-HF trial was to determine if PUFA could improve morbidity and mortality in patients with symptomatic heart failure of any cause.
Patients with New York Heart Association heart failure class II-IV, irrespective of left ventricular ejection fraction, were randomly assigned to 1g PUFA (n=3494) or placebo (n=3481). Median follow up was 3.9 years; the primary endpoints were time to death, and time to death or admission to hospital for a cardiovascular cause. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (hazard ratio, 0.91; p=0.041). 1981 (57%) patients in the PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (hazard ratio, 0.92; p=0.009).
In absolute terms the results suggest that 56 patients would need to be treated for a median of 3.9 years to avoid one death. Furthermore, PUFAs are cost-effective and have a low incidence of side-effects. Although two large-scale trials have now shown the clinical benefit of the drug, the exact mechanism of its action remains to be defined. Nonetheless, the results are encouraging given that a further paper from the GISSI-HF group, looking at the effect of rosuvastatin 10mg in heart failure, failed to show any benefit.
- GISSI-HF investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008; DOI: 10.1016/S0140-6736(08)61241-6.
- GISSI-HF investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008; DOI: 10.1016/S0140-6736(08)61241-6.
- Fonarow GC. Statins and n-3 fatty acid supplementation in heart failure. Lancet 2008; DOI: 10.1016/S0140-6736(08)61239-8.