HOUSTON — Daily oral fish oil supplementation led to remarkable improvements in cardiovascular outcomes in a high-risk population of patients receiving hemodialysis, according to the results of a randomized clinical trial with a follow-up of 3.5 years, prompting cautious optimism from experts.

“This is a major achievement,” said David Charytan, MD, director of the Division of Nephrology at the NYU Grossman School of Medicine, New York City, speaking as a discussant at the presentation of the findings here at Kidney Week 2025: American Society of Nephrology’s Annual Meeting.

“To the best of my knowledge, [this] is the first large outcome study to show a cardiovascular risk reduction in dialysis patients,” said Charytan. 

Calling it “incredibly exciting,” he noted that “we should not stop at one study. We need more data from a large, well-powered trial to confirm these results and get a better understanding.”

The study was simultaneously published in the New England Journal of Medicine. 

Patients on hemodialysis have an exceptionally high cardiovascular disease risk, with rates of cardiovascular mortality that are more than 20 times higher than the general population, first author Charmaine E. Lok, MD, of the University Health Network, University of Toronto, Canada, told meeting attendees.

Notably, however, many of the most common pharmacotherapies for cardiovascular disease in the general population — including statins, ACE inhibitors, and angiotensin receptor blockers — have failed to show benefit in these patients.

Although the benefits of fish oil and omega-3 fatty acids have been inconsistent for some indications, EPA and DHA, the active ingredients in omega-3 polyunsaturated fatty acids, have nevertheless been shown, separately and together, to have potentially important antithrombotic, anti-inflammatory, and antiarrhythmic properties, the study authors explained.

PISCES: Fish Oil in the Dialysis Population

To investigate those effects in the dialysis population, the researchers conducted the PISCES study, involving 1228 adult participants who were receiving maintenance hemodialysis at 26 sites in Canada and Australia between November 2013 and July 2019.

Patients were randomized 1:1 to treatment either with fish oil, containing 4 g of n-3 polyunsaturated fatty acids (n = 610, with 1.6 g of EPA and 0.8 g of DHA), or a corn-oil placebo (n = 618).

After a 3.5-year follow-up, the results showed substantially greater improvements in the endpoint composite of 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. 

Among those treated with fish oil, the primary endpoint was 158 events (or 0.31 per 1000 patient-days) compared with 309 events (or 0.61 per 1000 patient-days) in the placebo group (hazard ratio [HR], 0.57; 95% CI, 0.47-0.70; P < .001), representing a 43% lower risk with fish oil supplementation.

Of note, the results were similar regardless of whether or not the patient had prior cardiovascular events (HR, 0.50 and 0.55, respectively).

“We know that if someone has a cardiac event, they are more likely to have a future event, yet these results showed that patients who took fish oil and had experienced a prior cardiovascular event actually had the same risk as a placebo patient who did not have a previous cardiovascular event,” Lok noted.

The extended primary endpoint of the cardiovascular composite that included noncardiac causes of death was also lower in the fish oil group, with a hazard ratio of 0.77 (95% CI, 0.65-0.90).

Secondary endpoints, including specific components of the primary endpoint, also showed significant benefit of fish oil over placebo, with the fish oil group having lower rates of cardiac death (HR, 0.55), fatal and nonfatal myocardial infarction (HR, 0.56), peripheral vascular disease leading to amputation (HR, 0.57), fatal and nonfatal stroke (HR, 0.37), and a first cardiovascular event or death from any cause (HR, 0.73).

Serious bleeding occurred in 4.8% of participants in the fish oil group, and in 7.6% in the placebo group. There were no significant differences between the groups in terms of adherence to the regimens or other adverse events.

The authors note that the results are consistent with smaller previous observational studies suggesting that oral supplementation with n-3 fatty acids may reduce the risk of cardiovascular events in patients receiving hemodialysis. The current study also confirms findings from their own previous study, published in 2012, showing some key benefits of the fish oil supplementation on graft patency in patients with new synthetic arteriovenous hemodialysis grafts, as well as lower rates of thrombosis and corrective interventions. 

‘Landmark Trial’ — but Practice Changing?

In discussing the study’s clinical implications, Charytan pointed to the less striking mortality outcomes. 

“I think we do need to figure out why, if the cardiovascular risk reduction was so impressive, there doesn't seem to be nearly as much effect on all-cause mortality,” he said.  

In addition, the study had a dropout rate of 24%, which is hard to interpret because it occurred similarly in both groups, he noted. Importantly, the fish oil formulation used in the study is not FDA-approved in the United States.

Despite these caveats, Charytan said he does consider the trial to be a landmark study. For context, he cited reductions seen in kidney and cardiovascular events in other landmark studies, such as the CREDENCE trial of SGLT2-inhibitor canagliflozin and the FLOW trial of semaglutide, which had comparative risk reductions of 30% and 24%, respectively. 

“This [current study] shows nearly double those numbers, so I think we always want to have some caution when something is so surprisingly effective.” 

Start Prescribing While Waiting for Further Studies? 

Charytan was also co-author of  an editorial, published concurrently with the study, opining that“contemporary medicine is replete with examples in which potentially practice-changing, outsized results of early trials have failed to be replicated.”

“This situation suggests that we should pause before accepting such remarkable results as gospel,” the editorialists write.

That being said, Charytan said in his presentation the findings do suggest potentially important benefits of the study’s fish oil regimen for patients on dialysis.

“I think it would be very reasonable, given these results and given that it's the first study to show a reduction in cardiovascular mortality in the dialysis population, to start prescribing it for our patients,” he said. “I think in that context, both the cost and the lack of an apparent safety signal are quite reassuring.”

However, he added, “I would advocate that we should follow the lead of cardiologists and not stop at one study. I think we need more data.” 

Hope for the Dialysis Population 

Meg Jardine, MBBS, PhD, director of the University of Sydney NHMRC Clinical Trials Centre, and a professor of medicine at the University of Sydney, Australia, agreed that the results are eye-opening in the context of other kidney trials.

“The blockbuster SGLT2 inhibitor trials were transformative, and this was an even stronger effect size,” she told Medscape Medical News. 

A caveat is that “fish oil trials are complex,” she noted, so a key question will be whether the benefits are attributable to the specific fish oil formulation.

But it’s important to note the significance of such findings for the population of patients on dialysis, said Jardine.

“We've had so many wonderful outcomes in terms of chronic kidney disease prevention in the last 5 years that have been truly exciting,” she said. “However, there has not been a lot for the people who have already reached dialysis. 

“The study is very exciting for the kidney failure population,” she said. “This population has been truly resistant to many, many interventions, so while this needs to be confirmed, at least having activity and promise is important.”

Lok reported no relevant financial relationships. Charytan reported advisory or other relationships with Fresenius, CSL Behring, Boehringer Ingelheim, Eli Lilly, AstraZeneca, GSK, Merck LG Chem Pharma, Allena Pharma, and Alentis Therapeutics. Jardine reports advisory or other relationships with AstraZeneca, Bayer, Baxter, Boehringer Ingelheim, Chinook, CSL, Janssen, Novartis, OccuRx, Vifor.