The GISSI-HF trial: Effects of n-3 PUFA in 6,975 patients with symptomatic chronic heart failure

Researchers involved in the GISSI trial, concluded that simple, safe and cheap treatment with n-3 PUFA can provide a moderate beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with chronic heart failure, in a context of usual care.

Several epidemiological and experimental studies suggested that n-3 PUFA could exert favourable effects on the atherotrombotic cardiovascular disease including arrhythmias. The GISSI team investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause.

The GISSI researchers undertook a randomised, double blind, placebo controlled trial in 357 cardiology sites in Italy. They enrolled 6 975 patients with chronic heart failure of New York Heart Association class II-IV, assigned to n-3 PUFA 1 g daily or placebo. Patients were followed up for a median of 3•9 years. Primary end-points were time to death and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention-to-treat population.

Among the GISSI findings: 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (relative risk reduction 9%, 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 (relative risk reduction 8%, p=0•009). In absolute terms, 56 patients needed to be treated for 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In a per-protocol analysis performed in about 5000 full complier patients, the relative risk of death was reduced by 14% (p 0.004). Safety was excellent.

GISSI is endorsed by theAssociazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Firenze, Italy; Ist.Ricerche Farmacologiche Mario Negri, Milan, Italy and the Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.

The GISSI-HF trial was planned, conducted and analyzed by the GISSI group which has full ownership of the data.

This study is registered with Clinical trials.gov., number: NCT00336336.