Haemodialysis patients who take daily fish oil supplements experience serious cardiovascular events at a 40% lower rate than those receiving a placebo, a trial led by Australian and Canadian researchers has found.
The PISCES study, presented at the American Society of Nephrology’s Kidney Week 2025, randomised 1,228 dialysis patients to receive either 4g of n−3 polyunsaturated fatty acids daily or a placebo. Cardiovascular event outcomes were tracked over a maximum 3.5 years of follow up.
The rate of serious cardiovascular events was significantly lower in the group of patients receiving fish oil (HR 0.57), while the rate of cardiac deaths was also significantly reduced (HR 0.55).
The data also showed risk differences across a range of other outcomes favouring the fish oil group: a 44% lower risk of MI, a 43% lower risk of peripheral vascular disease resulting in amputation, and a 63% lower risk of stroke.
“The benefits associated with supplementation with n−3 fatty acids appeared to be consistent among participants with or without a history of cardiovascular events,” the researchers said in a simultaneous publication in New England Journal of Medicine [link here].
Adjunct professor, Medicine at Monash Health Kevan Polkinghorne was a co-author
Notably, the rate of serious cardiovascular events among patients in the treatment group who had experienced a previous cardiac event was similar to that of patients in the placebo group with no cardiovascular history.
The authors said their findings were aligned with a meta-analysis of previous trials suggesting oral supplementation of n−3 fatty acids could reduce the risk of cardiovascular death in dialysis patients.
However, the effects of fish oil on the rate of cardiovascular events in the general population are unclear, with studies producing mixed results.
Factors accounting for the different results seen between trials and the general vs haemodialysis population included composition of n-3 fatty acids used, the authors said.
Meanwhile, patients receiving haemodialysis have a unique metabolic and cardiovascular profile.
“Hemodialysis is characterized by a proinflammatory and proarrhythmic milieu, whereby cardiac stunning, ischemia, and vascular dysfunction are exacerbated by the rapid shifts in levels of fluid, sodium, potassium, and calcium,” the investigators said.
“One might speculate that such circumstances might also lead to arrhythmias.”
The stimuli for arrythmias may be lowered in the presence of n-3 fatty acids, the authors proposed.
“Because patients treated with hemodialysis have low levels of n−3 fatty acid, the cardioprotective properties of n−3 fatty acids may be especially beneficial.”
Are the results a red herring?
In a linked editorial, Harvard Medical School academic Associate Professor Finnian Mc Causland and NYU Langone nephrologist Dr David Charytan said some doctors might consider recommending their patients take fish oil supplements based on these results.
However, “history suggests that we should exercise caution until we are sure that there is truly a fish on the line”, they argued [link here].
While the study was to be commended for its success in recruitment and follow-up of dialysis patients, the results presented several unanswered questions, the editorial authors said.
“As the authors note in their discussion, issues related to generalisability and a lack of mechanistic understanding of the findings warrant caution.”
On the one hand, the reported differences in cardiovascular risks in the study were impressive and there were a lack of effective measures to prevent major cardiovascular events in these patients, the duo said.
“On the other hand, contemporary medicine is replete with examples in which potentially practice-changing, outsized results of early trials have failed to be replicated.”
The PISCES study also showed small numerical imbalances in infection and respiratory complications within the fish oil group when compared with the placebo, which needed further exploration.
These results set the scene for a confirmatory trial, associate professor Mc Causland and Dr Charytan said.
“Given the successful completion of PISCES, a confirmatory trial seems achievable and is certainly indicated.”