A colleague recently sent me a paper that had her hemodialysis (HD) unit buzzing. It had everyone asking:
Should all HD patients be recommended fish oil supplements?
So, for today’s journal club, let’s take a closer look at the PISCES study to see what the data actually tell us—and what it might (and might not) mean for practice.
The reference for today’s post is: Lok, Charmaine E., et al. “Fish-oil supplementation and cardiovascular events in patients receiving hemodialysis.” New England Journal of Medicine (2025).
Why Did the Researchers Do This Study?
In the general population, fish oil supplements and cardiovascular disease (CVD) have been studied for over 50 years. However, whether omega-3 fatty acids—specifically EPA and DHA—reduce cardiovascular events in adults receiving maintenance hemodialysis has remained unclear.
The PISCES investigators aimed to answer a straightforward but clinically important question:
Can omega-3 supplementation reduce serious cardiovascular events in people on HD?
What Type of Study Was It?
The Protection against Incidences of Serious Cardiovascular Events Study (PISCES) was a:
- Multi-centre
- Parallel-group
- Randomized
- Placebo-controlled clinical trial
In other words, this was a randomized controlled trial (RCT)—generally considered the gold standard for assessing cause-and-effect relationships.
Participants were randomized to receive either:
- Daily fish oil supplements, or
- Daily corn oil placebo
The study was conducted across 16 sites in Canada and Australia and included oversight by an independent data and safety monitoring committee, which adds to the study’s methodological rigour.
Who Was Eligible to Participate?
To be included, participants had to:
- Be 18 years or older
- Be receiving hemodialysis 3–4 times per week
- Be clinically stable
People were excluded if they:
- Had allergies to fish, soy, or corn
- Were already taking omega-3 supplements
What Supplement Did Participants Receive?
Participants in the intervention group received a steam-deodorized, citrus-flavoured omega-3 PUFA supplement.
- Dose: 4 × 1 g capsules per day
- Total daily omega-3 dose:
- 1.6 g EPA
- 0.8 g DHA
The placebo group received a citrus-flavoured corn oil supplement designed to match taste and appearance.
How Long Were Participants Followed?
Participants were followed for a median of 3.5 years after randomization—an impressively long follow-up period for a nutrition intervention trial in HD.
What Outcomes Were the Researchers Looking For?
Primary Outcome: Serious Cardiovascular Events
This included:
- Sudden or non-sudden cardiac death
- Fatal myocardial infarction (MI) or stroke
- Non-fatal MI
- Peripheral vascular disease resulting in amputation
- Non-fatal stroke
Notably, heart failure was excluded, as volume overload is common in the HD population and could confound results.
Importantly, all events were counted, meaning a single participant could contribute more than one event to the total.
Secondary Outcomes
- Cause-specific mortality
- Individual components of the primary outcome
- First cardiovascular event or death
How Were Outcomes Measured?
Outcomes were reported as:
- Number of events per 1,000 patient-days, and
- Percentage of participants experiencing an event
To calculate events per 1,000 patient-days, researchers divided the total number of events by total follow-up time and multiplied by 1,000.
The study accumulated:
- 1,394 patient-years of follow-up in the omega-3 group (610 participants)
- 1,382 patient-years in the placebo group (618 participants)
I’ll admit—reporting events per 1000 patient days can feel a bit abstract when we’re trying to translate findings to individual patients.
Did They Use an Intention-to-Treat Analysis?
Yes—and this is an important strength.
An intention-to-treat (ITT) analysis means participants were analyzed in the group they were originally randomized to, regardless of adherence.
Why does this matter?
- It reflects real-world practice
- It prevents cherry-picking of data
- It preserves the benefits of randomization
A helpful analogy: we can prescribe a medication (or supplement), but we can’t force someone to take it exactly as directed. ITT analysis assumes that reality—and that’s a good thing.
Who Were the Participants?
A total of 1,228 participants were randomized between 2013 and 2019. On average, the participants characteristics were:
- ~64 years old
- on dialysis for 3.7 years
- 62–63% male
- BMI of 27–28
- ~33% had a history of cardiovascular disease
- ~40% White
What Did They Find?
Serious Cardiovascular Events
- Omega-3 group: 158 events
- Placebo group: 309 events
Event rates:
- 0.31 events per 1,000 patient-days in the omega-3 group
- 0.61 events per 1,000 patient-days in the placebo group
That’s roughly a 40% lower event rate with omega-3 supplementation.
Mortality
- 173 deaths in the omega-3 group
- 195 deaths in the placebo group
Across all outcomes assessed, the omega-3 group consistently experienced fewer events, including among participants with prior cardiovascular disease.
Why Might the Results Have Been So Favourable?
The authors propose several explanations:
- Formulation matters
- The 40:20 ethyl ester formulation may cause fewer GI side effects, potentially improving adherence.
- Dose matters
- The total dose exceeded 1 g/day, which may be necessary to achieve cardiovascular benefit.
What Are the Limitations?
As with any trial, there are caveats:
- Participants were not followed if they switched to peritoneal dialysis or received a transplant
- Compliance was verified with blood testing only once (at 3 months)
- The authors could not confirm whether participants independently took omega-3 supplements outside the study
Key Takeaways for Dietitians
The PISCES study provides promising evidence that 4 g/day of omega-3 supplements (1.6 g EPA + 0.8 g DHA) may reduce serious cardiovascular events in adults receiving maintenance HD 3–4 times per week.
The study was well-designed and rigorously conducted. However, it’s important to keep a few things in perspective:
- Absolute event rates were relatively low
- The intervention added four additional pills per day
- HD patients already experience a high pill burden
So while omega-3 supplementation may represent an exciting adjunct therapy, decisions should be individualized—balancing potential benefit against pill burden and patient preference.
