Level 1: Likely reliable evidence

The GISSI-HF randomized placebo-controlled trial also evaluated n-3 polyunsaturated fatty acids (PUFAs) in 357 cardiology or internal medicine centers in Italy (Lancet. 2008;372:1223-1230). Patients with chronic heart failure (NYHA class II-IV) (N=7,046, mean age 67 years) were randomized to n-3 PUFAs 1 g vs. placebo once daily. The n-3 PUFA preparation contained 850-882 mg of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) as ethyl esters in average ratio 1:1.2. Median follow-up was 3.9 years. Seventy-one patients (1%) from one site were not analyzed due to inadequate data.

On analysis, n-3 PUFAs were associated with decreases in death from any cause (NNT 56), death from cardiovascular cause (NNT 63), and hospital admission for cardiovascular reasons (NNT 59). There were no significant differences in rates of sudden cardiac death, MI, or admission for heart failure, but there were nonsignificant trends toward reduced rates with n-3 PUFAs. There were no significant differences in rates of stroke. By the end of the trial, the percentages of patients no longer taking the study drug or placebo were similar (29% with treatment vs. 30% with placebo). GI disorders were the most frequently reported adverse reaction (3% in both groups).

The study was partially funded by a PUFA manufacturer; the drug used in the study appears similar to (but not the same as) the prescription drug Lovaza. According to an American Heart Association scientific statement, dietary sources of EPA and DHA include fatty fish, such as salmon (about four ounces provides the same amount of PUFAs used in the study).

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