Fish Oil Supplementation and Cardiovascular Events in Hemodialysis

Key Takeaways

• Fish oil was associated with a lower rate of serious cardiovascular events than corn-oil placebo during follow-up.
• The extended composite outcome and several individual cardiovascular outcomes also favored fish oil.
• Adherence and overall adverse-event incidence were similar, and the authors concluded that daily n-3 fatty acid supplementation was associated with a lower rate of serious cardiovascular events than placebo.

In an NEJM trial, adults receiving maintenance hemodialysis who took daily fish oil had a lower rate of serious cardiovascular events than those given corn-oil placebo over 3.5 years, with a hazard ratio of 0.57. The difference was seen in the composite of serious cardiovascular events rather than any single component outcome.

The double-blind, randomized, placebo-controlled trial was conducted at 26 sites in Canada and Australia. The trial enrolled 1228 adults receiving maintenance hemodialysis and randomized 610 to fish oil and 618 to placebo between November 28, 2013, and July 22, 2019. The active regimen was daily fish oil containing 4 g of n-3 polyunsaturated fatty acids, including 1.6 g of EPA and 0.8 g of DHA. Published online November 7, 2025, and later in the January 8, 2026, issue, the study prespecified a serious cardiovascular composite as its main efficacy assessment.

The primary end point combined all serious cardiovascular events, including sudden and nonsudden cardiac death, fatal and nonfatal myocardial infarction, peripheral vascular disease leading to amputation, and fatal and nonfatal stroke. Secondary assessments extended that composite to include noncardiac causes of death and examined individual components as well as first cardiovascular event or death from any cause. Event rates were 0.31 and 0.61 per 1000 patient-days, favoring fish oil with a hazard ratio of 0.57, 95% confidence interval 0.47 to 0.70, and P<0.001. The extended primary end point also favored fish oil, with hazard ratio 0.77, while cardiac death and myocardial infarction had hazard ratios of 0.55 and 0.56. Peripheral vascular disease with amputation, stroke, and first cardiovascular event or death from any cause had hazard ratios of 0.57, 0.37, and 0.73, respectively.

Adherence to the trial regimen did not differ meaningfully between the fish-oil and placebo groups. Overall adverse-event incidence also did not differ meaningfully between groups. The authors concluded that among participants receiving maintenance hemodialysis, daily supplementation with n-3 fatty acids was associated with a lower rate of serious cardiovascular events than placebo.