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

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Abstract
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.