Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure

Eur J Heart Fail. 2004 Aug;6(5):635-41. doi: 10.1016/j.ejheart.2004.03.001.


Background: The GISSI Heart Failure project is a large-scale, randomized, double-blind study designed to investigate the effects of n-3 polyunsaturated fatty acids and rosuvastatin on mortality and morbidity in patients with symptomatic heart failure.

Methods and results: Patients with New York Heart Association classes II to IV heart failure, already receiving optimized recommended therapy, will be recruited in a nation-wide network of more than 300 cardiology and internal medicine services to be randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily) or the corresponding placebo. Patients with no clear indication or contraindication to cholesterol-lowering therapy will be further randomized to receive low-dose rosuvastatin (10 mg daily) or placebo. According to data available in heart failure registries, it is expected that 70% of the patients will be suitable to enter both components of the trial, which assume the same co-primary endpoints: (a) 15% reduction of all-cause mortality and (b) 20% reduction of all-cause mortality or cardiovascular hospitalizations. The trial is event-driven and will continue either until at least 1252 deaths have been recorded or a reduction of all-cause mortality will satisfy the significance boundaries, which have been established to stop the study. The recruitment of the planned sample size of approximately 7000 patients randomized in the n-3 PUFA trial is expected to be completed within 18 months from the trial start. As of February 29, 2004, 4624 heart failure patients have been included in the trial.

Conclusion: The GISSI-HF project, with its protocol articulated into two independent randomization schemes, has the aim and the power to verify the hypothesis that n-3 polyunsaturated fatty acids and rosuvastatin can favorably modify the prognosis of patients with symptomatic heart failure.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated / therapeutic use*
  • Fluorobenzenes / therapeutic use*
  • Heart Failure / drug therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypolipidemic Agents / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Research Design
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use*
  • Triglycerides / therapeutic use*


  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Pyrimidines
  • Sulfonamides
  • Triglycerides
  • Pikasol
  • Rosuvastatin Calcium