PISCES: Fish Oil Slashes Cardiovascular Event Risk of Maintenance Dialysis

Patients on maintenance hemodialysis receiving daily fish oil had significantly lower rates of serious cardiovascular (CV) events than those receiving placebo.1,2

These findings, from the PISCES trial, were simultaneously published in New England Journal of Medicine and presented at the American Society of Nephrology (ASN) Kidney Week 2025, held November 5-9, 2025, in Houston, Texas, by Charmaine E. Lok, MD, MSc, Professor of Medicine, University Health Network, Toronto, Ontario, Canada.

“So, should fish oil now be recommended for our patients receiving hemodialysis? On the one hand, the reported differences in cardiovascular risk are impressive (with upper boundaries of 95% confidence intervals well below unity), so it seems unlikely that these findings are due to chance… 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. This situation suggests that we should pause before accepting such remarkable results as gospel,” Finnian R. Mc Causland, MBBCh, MMSc, Brigham and Women’s Hospital, Harvard Medical School, and David M. Charytan, MD, Division of Nephrology, New York University Grossman School of Medicine, wrote in a related editorial.3

PISCES was a multicenter double-blind placebo-controlled randomized controlled trial that evaluated the effect of daily oral supplementation with 4 g of n−3 polyunsaturated fatty acids (PUFA; 1.6 g EPA, 0.8 g DHA; n = 610) compared with placebo (n = 618) in 1228 adults on maintenance hemodialysis across 26 sites for 3.5 years. The trial primarily assessed the rate of all serious CV events, including CV death, non-fatal myocardial infarction, stroke, and peripheral vascular disease requiring amputation. Secondary outcomes further assessed all-cause mortality and individual components of the primary outcome.1,2

Lok and colleagues found that the rate of serious cardiovascular events was significantly lower in the fish-oil group (0.31 per 1000 patient-days) than in the placebo group (0.61 per 1000 patient-days; hazard ratio [HR], 0.57; 95% CI, 0.47-0.70; P <.001). Including noncardiac causes of death also yielded a lower HR of 0.77 (95% CI, 0.65-0.90) compared to placebo.1,2

Specifically, the HR for cardiac death was 0.55 (95% CI, 0.40-0.75); for fatal and nonfatal myocardial infarction, 0.56 (95% CI, 0.40-0.80); for peripheral vascular disease leading to amputation, 0.57 (95% CI, 0.38-0.86); for fatal and nonfatal stroke, 0.37 (95% CI, 0.18-0.76); and for a first cardiovascular event or death from any cause, 0.73 (95% CI, 0.61-0.87).1,2

Importantly, investigators also found that benefits were consistent among those with prior CV event (HR, 0.50; 95% CI, 0.37-0.67) and those without prior CV events (HR, 0.55; 95% CI, 0.40-0.76; P < 0.000) prior CV events. There were no safety signals in the trial, with similar rates of adverse events and similar adherence rates between groups.1,2

“Given the successful completion of PISCES, a confirmatory trial seems achievable and is certainly indicated. Until then, some physicians may want to consider recommending that their patients use n−3 polyunsaturated fatty acids, but history suggests that we should exercise caution until we are sure that there is truly a fish on the line,” Mc Causland and Charyton wrote.3

Mc Causland and Charyton also pointed out limitations of the trial that Lok and colleagues acknowledged in their paper, including issues related to generalizability and a lack of mechanistic understanding of the findings, as well as small numerical imbalances in the incidence of infections and respiratory complications with n−3 PUFA which require further exploration, given that infections are the second leading cause of death among patients receiving maintenance hemodialysis.3

References

1. Lok CE, Hemmelgarn B, Moist LM, et al. Protection Against Incidences of Serious Cardiovascular Events Study with Daily Fish Oil Supplementation in Patients on Dialysis (PISCES). Presented at: ASN Kidney Week. Houston, Texas. November 05-09, 2025. #FR-OR082

2. Lok CE, Farkouh M, Hemmelgarn BR, et al. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. Published online November 7, 2025. doi: 10.1056/nejmoa2513032

3. Mc Causland FR, Charytan DM. Fish Oil for Patients Receiving Hemodialysis — Red Herring or Great Catch? N Eng J Med. Published online November 7, 2025. doi: 10.1056/nejme2515057