The GISSI-HF trial suggests long-term treatment with n-3 PUFAs provides moderate clinical benefits for chronic heart failure patients

August 31, 2008 by Leah H. Biller [1]

ESC Congress 2008- Munich, Germany: The GISSI-HF study demonstrates that among chronic heart failure patients, treatment with n-3 polyunsaturated fatty acids (n-3 PUFAs) in addition to standard best care practices results in lower rates of mortality and cardiovascular-related hospital admissions. These results were presented by Dr. Luigi Tavazzi on behalf of the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) group as part of the ESC 2008 Congress Hot Line I .

Clinical interest in n-3 PUFAs began over 30 years ago, when researchers found better cardiovascular health in Inuit populations consuming regular quantities of fish versus other groups with lower intakes of fish . Scientists later were able to determine that it was the presence of n-3 PUFAs in the fish that lead to its anti-arrhythmic properties. Recent studies have continued to explore the cardiovascular benefits of increased consumption of n-3 PUFAs. In the GISSI-HF trial, researchers investigated the impact of n-3 PUFAs on the mortality and morbidity of chronic heart failure patients.

In this randomized, double blind, placebo-controlled trial, 6975 patients with chronic heart failure of NYHA class II-IV were given a daily 1 g n-3 PUFA or placebo supplement. This was a multicenter study with patients enrolled in 357 sites in Italy. Follow-up occurred for a median of 3.9 years, and the primary endpoints were time to death and time to death or to cardiovascular-related hospital admission.

The GISSI-HF study found a 9% risk reduction (p=0.041) of death from any cause for patients taking the n-3 PUFA supplement versus placebo (27% [n=955) died in the n-3 PUFA group versus 29% [n=1014] in the placebo group). Similarly, an 8% relative risk reduction (p=0.009) was found between study arms for death or hospitalization for cardiovascular reason (57% [n=1981] had an event in the n-3 PUFA group versus 59% [n=2053] in the placebo group). These results translate in absolute terms such that for every 56 patients treated with n-3 PUFAs for 3.9 years, one death would be avoided, and for every 44 patients treated with n-3 PUFAs for 3.9 years, one death or cardiovascular-related hospital admission would be avoided. The GISSI investigators also performed a per-protocol analysis in 5000 full complier patients which showed a relative risk reduction for death of 14% (p=0.004).

The findings of this study contribute to the body of knowledge concerning the advantages of n-3 PUFAs that began in the 1970s. Treatment with inexpensive and safe n-3 PUFA supplements, in conjunction with current best care practices, was shown to provide moderate benefits in cardiovascular outcomes for patients with chronic heart failure. These results suggest the value (both clinical and financial) of daily n-3 PUFA therapy for patients in this disease population.

The GISSI-HF trial was endorsed by: Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Firenze, Italy; Ist.Ricerche Farmacologiche Mario Negri, Milan, Italy; and Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy. Funding was also provided by SPA, Pfizer, Sigma Tau and AstraZeneca. The GISSI-HF trial was planned, conducted and analyzed by the GISSI groups which has full data ownership.

Reviewed by C. Michael Gibson, M.S., M.D.