PUFA provide modest benefit in HF

31 August 2008

MedWire News: 31 August 08 – Taking a daily dose of n-3 polyunsaturated fatty acids (PUFA) results in a modest reduction in mortality among patients with chronic heart failure (HF), results from the GISSI-HF trial reveal.

Although the benefits seen with daily PUFA were only modest, the investigators suggest the intervention could provide an attractive addition to optimal medical therapy, being well tolerated, easy to take, and relatively cheap.

The GISSI-HF trial involved two nested studies designed to concurrently test the mooted clinical benefits of PUFA and statins in HF. PUFA have been shown in preclinical studies to have a large number of potentially beneficial effects on cardiovascular function that could impact on the syndrome of HF, while epidemiologic studies have shown that consumption of fish rich in PUFA is linked to reduced cardiac death rates.

A total of 6975 patients with New York Heart Association (NYHA) class II-IV HF of any cause and with any left ventricular ejection fraction were randomly assigned to receive n3-PUFA 1 g (805-882 mg eicosapentaenoic acid and docosahexaenoic acid in the average ratio 1:1.2) daily or placebo. Of these patients, 4574 considered eligible for treatment with a statin were also randomized to rosuvastatin 10 mg daily or placebo.

The results were presented today at the European Society of Cardiology (ESC) annual Congress in Munich, Germany, and simultaneously published online by The Lancet.

Chair of the GISSI-HF steering committee Luigi Tavazzi (Fondazione Policlinico San Matteo, IRCCS, Pavia, Italy) presented the results of the PUFA intervention at the ESC congress. He reported that, over a median follow-up of 3.9 years, all-cause death occurred in 27.3% of patients who took PUFA compared with 29.1% of those who received placebo. Thus PUFA resulted in a 1.8% absolute risk reduction, which translated into a 9.0% reduction in hazard ratio (HR) after adjusting for unbalanced variables (p=0.041).

Similarly, PUFA-treated patients had a 2.3% absolute reduction in all-cause death or hospital admission for cardiovascular reasons, giving an 8.0% reduction in the adjusted HR (p=0.009) relative to placebo-treated patients.

The benefits of PUFA supplementation only became apparent after about 2 years of treatment. Tavazzi noted that the absolute risk reductions achieved with PUFA mean that 56 patients would need to be treated over a 4-year period to prevent one death, while 44 would need to be treated to avoid a death or a hospital admission for cardiovascular causes.

Tavazzi highlighted that the rate of presumed arrhythmic death was no different between treatment groups but that PUFA-treated patients had a 28% lower adjusted hazard for hospitalization for ventricular arrhythmias.

Noting that that there was no difference in adverse events between groups, he also reported that the per protocol analysis in 4994 patients who completed follow-up showed a greater reduction of 12-14% in all-cause death and death or hospitalization due to cardiovascular cause with PUFA. He also emphasized that the modest benefits in the main analysis were seen on a background of optimal medical therapy.

Invited discussant at the ESC presentation, Michel Komajda (Paris and Pitie Salpetriere Hospital, France), questioned what the mechanism for the observed modest benefit in the co-primary endpoints could be, especially given that sudden death did not differ between groups.

Nevertheless, he concurred with Tavazzi that the benefit was seen across a broad range of patients who were being optimally treated and that the intervention could offer a simple and well-tolerated additional measure in patients having to take many medications.

Writing in an editorial accompanying the GISSI-HF papers in The Lancet, Gregg Fonarow (University of California, Los Angeles, USA) expressed a similar view.

He wrote: “While questions remain about the mechanism of action, optimum dosing, and formulation, supplementation with PUFA should join the short list of evidence-based life-prolonging therapies for HF.”

European Society of Cardiology Congress; Munich, Germany: 30 Aug – 3 Sept 2008