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Supplementation with omega-3 polyunsaturated fatty acids improved left ventricular function in patients with mild-to-moderate chronic heart failure due to dilated cardiomyopathy, a randomized, placebo-controlled trial showed.

After one year of treatment, patients who took the supplements had a significant improvement of 10.4% in left ventricular ejection fraction, compared with a decline of 5% in patients on placebo (P<0.001), according to Mihai Gheorghiade, MD, of Northwestern University in Chicago, and colleagues.

Omega-3 supplementation also improved peak oxygen uptake by 6.2% (versus a worsening of 4.9% with placebo) and exercise duration by 7.7% (versus a reduction of 5.8% with placebo), the researchers reported online in the Journal of the American College of Cardiology.

None of the patients taking the supplements moved to a higher New York Heart Association functional class, whereas 28.8% of those on placebo worsened (P<0.001).

Given the study results, which were originally presented last September at the Heart Failure Society of America meeting in San Diego, "larger studies are in order to confirm our findings," Gheorghiade and his colleagues wrote.

The findings add support to a larger trial -- GISSI-HF -- that showed that long-term treatment with a lower dose of omega-3 polyunsaturated fatty acids reduced mortality and cardiovascular hospitalizations in patients with chronic heart failure.

But until the current trial was conducted, it had been unknown whether supplementation would improve left ventricular function.

Gheorghiade and his colleagues recruited 133 patients from a single clinic at the University of Brescia in Italy. All had NYHA class I or II heart failure due to nonischemic dilated cardiomyopathy with minimal symptoms. All were on standard, evidence-based therapy with an ACE inhibitor, an angiotensin II receptor blocker, a beta-blocker, and furosemide. Many patients were also taking an aldosterone receptor blocker.

The researchers randomized the patients in roughly equal numbers to supplementation with omega-3 polyunsaturated fatty acids or placebo.

Active treatment was given in 1-gram capsules containing 850 to 882 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters. Patients took five capsules daily for the first month followed by two capsules daily for the rest of the study.

After 12 months there were significant between-group differences in left ventricular ejection fraction (the primary endpoint), peak oxygen consumption, exercise duration, and functional class (P<0.001 for all).

Left ventricular diastolic function -- according to deceleration time and diastolic function score -- improved in the supplementation group and worsened in the placebo group.

Consistent with experimental evidence that omega-3 polyunsaturated fatty acids reduce inflammation, levels of three inflammatory cytokines -- tumor necrosis factor (TNF)-alpha, interleukin-6, and interleukin-1 -- significantly increased in the placebo group and decreased in the supplementation group (P<0.001).

All of these changes may have been responsible for the significant reduction in the rate of cardiovascular hospitalizations in the supplementation group (6% versus 30%, P=0.0002), the researchers noted.

Supplementation was well tolerated, with no serious adverse events.

The furosemide dose was maintained in 61% of the supplementation group and reduced in 39%. In contrast, the dose was maintained in 76% of the placebo group and increased in 24%. There were no changes to any of the other medications.

In an accompanying editorial, W.H. Wilson Tang, MD, and Michael Samara, MD, of the Cleveland Clinic, noted that the question of whether higher doses of omega-3 polyunsaturated fatty acids (PUFAs) could achieve better outcomes remained unknown.

"This is a critical question to address, since prescription-strength, high-dose omega-3 PUFA regimens differ significantly from the lower and inconsistent dosages found in over-the-counter supplements," they wrote.

"In other words, simply telling patients to take 'fish-oil' supplements without understanding the adequacy of dosing is unlikely to yield the same benefits as promised in the current study."

Gheorghiade and his colleagues acknowledged some limitations of the study, including the use of a single center, the small sample size, the limited number of clinical events, and the lack of tissue Doppler measurements of diastolic function.

In addition, they wrote, the results cannot be generalized to patients with more advanced heart failure, those with disease from other causes, or those not receiving optimal medical therapy.