Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 18757090 · doi:10.1016/S0140-6736(08)61239-8
What was done
A randomized, double-blind, placebo-controlled trial conducted across 357 centers in Italy evaluated patients with New York Heart Association class II–IV chronic heart failure of any cause and left ventricular ejection fraction. A total of 6,975 participants were allocated via concealed computerized randomization to receive either 1 g daily of n-3 polyunsaturated fatty acids (n=3494) or placebo (n=3481) and were followed for a median of 3.9 years (IQR 3.0–4.5). Co-primary endpoints were time to death from any cause, and time to death or hospital admission for cardiovascular reasons, evaluated by intention-to-treat analysis.
What was found
- All-cause mortality: 955 (27%) in the n-3 PUFA group vs 1,014 (29%) in the placebo group (adjusted HR 0.91, 95.5% CI 0.833–0.998, p=0.041; NNT = 56 over 3.9 years). - Composite of death or cardiovascular hospitalization: 1,981 (57%) in the n-3 PUFA group vs 2,053 (59%) in the placebo group (adjusted HR 0.92, 99% CI 0.849–0.999, p=0.009; NNT = 44 over 3.9 years). - Adverse events: Gastrointestinal disorders were the most frequent adverse reaction, occurring in 96 (3%) patients on n-3 PUFA versus 92 (3%) on placebo.
Why it matters
This large trial showed that adding 1 g/day of omega-3 fatty acids to standard care provides a small but statistically significant reduction in all-cause mortality and cardiovascular hospitalizations in symptomatic heart failure patients, with a favorable safety profile.
Limits
The absolute risk reduction is modest (2% absolute difference in mortality; NNT of 56 over ~4 years), with the upper bound of the mortality hazard ratio close to 1.00 (0.998). The trial was conducted entirely in Italy, where background dietary omega-3 intake may differ from other populations, potentially limiting generalizability. The abstract does not provide subgroup analyses by heart failure etiology, baseline ejection fraction, or baseline dietary intake.
Cited by
- contradicts Vascepa is the only omega-3 formulation approved by the FDA for reducing cardiovascular event risk, whereas Lovaza has never been tested in a cardiovascular outcome trial.