title: Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause.
  
  
  METHODS
  We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3.9 years (IQR 3.0-4.5). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336.
  
  
  RESULTS
  We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0.91 [95.5% CI 0.833-0.998], p=0.041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0.92 [99% CI 0.849-0.999], p=0.009). In absolute terms, 56 patients needed to be treated for a median duration of 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group).
  
  
  CONCLUSIONS
  A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchioli
authors.forename: Simona
authors.initials: S
authors.lastname: Barlera
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Franzosi
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Donata
authors.initials: D
authors.lastname: Lucci
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Nicolosi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Porcu
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni