© 2004 European Society of Cardiology
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*
a Policlinico San Matteo, IRCCS, Pavia Italy
b Istituto di Ricerche Farmacologiche ‘Mario Negri Milano, Italy
c Centro Studi ANMCO Firenze, Italy
d Ospedale Santa Maria degli Angeli Pordenone, Italy
e Ospedale San Michele ‘G. Brotzu’ Cagliari, Italy
f Consorzio Mario Negri Sud Santa Maria Imbaro, Italy
* Corresponding author. Present address: GISSI-HF Co-ordinating Centre, Centro Studi ANMCO, Via La Marmora 34, Firenze, Italy. E-mail address: gissihf{at}anmco.it
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Abstract |
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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.
Key Words: Heart failure • Polyunsaturated fatty acids • Statins • Mortality
Received September 12, 2003; Revised September 19, 2003; Accepted March 1, 2004
GISSI-HF Investigators: GISSI—Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca—is endorsed by Associazione Nazionale Medici Cardiologi Ospedalieri—ANMCO—and by Istituto di Ricerche Farmacologiche ‘Mario Negri’.
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