Omega-3 Breakthrough Cuts Major Heart Events by 43%

We’ve had failure after failure after failure, but it now looks like we finally have a breakthrough from a new Omega-3 study.

And this breakthrough has important implications for your health and mine.

Because despite the initial promising studies on Omega-3 and heart health, things took a turn for the worse.

Table of Contents

• Early Promise, Followed by Disappointments
• A New Breakthrough in High-Risk Patients
• What This Means for the Rest of Us
• References

Early Promise, Followed by Disappointments

Despite the initial promising studies on Omega-3 and heart health, the research journey has been rocky.

A 2006 systematic review found that increased consumption of n-3 fatty acids from fish or fish-oil supplements — but not alpha-linolenic acid — reduced the rates of all-cause mortality, cardiac and sudden death, and possibly stroke [1].

But by 2012, things started to go horribly wrong.

In 2012, the findings were published from a large study of 12,536 patients who had type 2 diabetes or were at elevated risk of it. These patients were also at high risk for cardiovascular events like heart attacks and strokes. One group in the study took a 1 g Omega-3 supplement daily [2].

After a median follow-up of 6.2 years, heart-related deaths in the Omega-3 group weren’t significantly lower than in the placebo group. The incidence of the primary outcome was:

• 9.1% in the Omega-3 group (574 patients)
• 9.3% in the placebo group (581 patients)
• Hazard ratio: 0.98 (95% CI: 0.87 to 1.10; P=0.72) [2]
  

There also wasn’t a significant difference in heart attacks and strokes. For major vascular events:

• Omega-3 group: 16.5% (1034 patients)
• Placebo group: 16.3% (1017 patients)
• Hazard ratio: 1.01 (95% CI: 0.93 to 1.10; P=0.81) [2]

And then came the STRENGTH trial, published in 2020. This was a massive study of over 13,000 patients taking statins who were at high risk for heart problems. It spanned 22 countries across North America, Europe, South America, Asia, Australia, New Zealand, and South Africa [3].

The study tested high-dose Omega-3 fatty acids (EPA and DHA) compared with corn oil.

It was actually stopped early, because the data was clear: no significant difference when it came to major cardiovascular events like heart attacks and strokes.

• Hazard ratio: 0.99 (95% CI: not provided in summary) [3]
  

The only bright spot came from the VITAL trial in 2018. It included 25,871 participants with a follow-up period of 5.3 years. One group took 1 g of Omega-3 daily [4].

That group had a 28% lower risk of heart attack compared to placebo.

• Hazard ratio for total myocardial infarction: 0.72 (95% CI: 0.59 to 0.90) [4]
  

To try and make sense of the conflicting data, the Mayo Clinic conducted a large meta-analysis. This included 40 studies and 135,267 participants.

Here’s what they found:

• Heart attack risk dropped by 13%
  • Relative risk (RR): 0.87 (95% CI: 0.80 to 0.96)
• Fatal heart attack risk dropped by 35%
  • RR: 0.65 (95% CI: 0.46 to 0.91)
• Number needed to treat (NNT):
  • 272 for heart attacks
  • 128 for fatal heart attacks [5]

But there remained a number of important questions — about dosing, the best forms of Omega-3, and the risks of a dangerous heart rhythm problem known as atrial fibrillation. We’ll come back to that in a moment.

Overall, from the VITAL trial and the Mayo Clinic’s meta-analysis, we’ve seen some real and important benefits — even though the early hype has cooled a bit.

A New Breakthrough in High-Risk Patients

It was because of these potential heart health benefits that researchers wanted to test Omega-3 in a group of patients where nothing else seemed to work — where everything seemed to fail.

What they discovered appears to be a game changer. And it has important implications for the rest of us, too.

The patient group in question is those with kidney failure who are undergoing dialysis. Dialysis is where a machine filters your blood because your kidneys no longer can.

This is a surprisingly large group — estimated at around 3 million people globally. But the dialysis machines just don’t do as good a job as our kidneys.

One of the major problems dialysis patients face is a very high mortality rate, especially from heart disease. In fact, around 40–50% of those on dialysis die from heart-related problems [6].

And yet finding interventions that help bring this number down has been extremely difficult.

Example 1: Statins

These cholesterol-lowering drugs have shown impressive benefits in the general population.
For example:

• Statins reduce cardiovascular events by ~25% per 38.6 mg/dL LDL reduction
• Long-term LDL-C reduction (over 40 years) may lower cardiovascular mortality by 50–55%
• And the largest absolute benefits occur in high-risk groups [7]
  

But in dialysis patients, statins have been a disappointment.

A 2015 meta-analysis found no significant impact on all-cause or cardiovascular mortality [8].

Example 2: Spironolactone

This is a medication commonly used for heart failure and hypertension.

In a study of veterans with heart failure and preserved ejection fraction, spironolactone reduced all-cause mortality by 21%.

• Hazard ratio: 0.79 (95% CI: 0.71–0.87; P<0.0001) [9]
  

But when tested in dialysis patients, it made no difference.
A 2025 systematic review concluded it had little to no effect on cardiovascular mortality in this population [10].

The New Omega-3 Study

Against this backdrop of repeated failures, researchers asked a bold question:

Could a fish oil supplement — something simple — succeed where powerful heart medications failed?

The study was large and well-designed:

• Conducted across 26 sites in Canada and Australia
• Included 1,296 adult dialysis patients
  
• One group received 4 g/day of Omega-3
  • (1.6 g EPA and 0.8 g DHA)
• The other group received a corn oil placebo
• Follow-up period: 3.5 years [11]

The results were startling.

Major Cardiovascular Events

These included heart attacks, strokes, and heart-related deaths.

• The Omega-3 group had a 43% lower risk
  
  • Hazard ratio: 0.57 (95% CI: 0.47 to 0.70; P<0.001) [11]

Specific Outcomes:

• Cardiac deaths:
  • 45% lower risk
    
  • HR: 0.55 (95% CI: 0.40 to 0.75)
    
• Heart attacks (fatal and nonfatal):
  • 44% lower risk
  • HR: 0.56 (95% CI: 0.40 to 0.80)
    
• Peripheral vascular disease leading to amputation:
  • 43% lower risk
    
  • HR: 0.57 (95% CI: 0.38 to 0.86)
    
• Strokes (fatal and nonfatal):
  • 63% lower risk
  • HR: 0.37 (95% CI: 0.18 to 0.76) [11]

This level of benefit was completely unexpected — and extremely promising.

What This Means for the Rest of Us

So this new study provides some really exciting data on the potential cardiovascular benefits of Omega-3.

The promise here for an extremely high-risk group is huge.

But most of us don’t have end-stage kidney disease. So what does this mean for the rest of us?

Well, the story so far has a bit of tension.

On the one hand, we’ve seen impressive early studies and meta-analyses showing benefits.

On the other hand, we’ve had some major disappointments, like the STRENGTH trial, where researchers saw no benefit despite a large sample size and long follow-up.

But this new trial does two things:

1. It provides additional support to the existing evidence that Omega-3 likely has real potential to protect heart health

2. It suggests we may see stronger and more consistent results in the general population — if we get the dosing and formulation right

And dosing, as we’ve seen, is tricky.

In the Mayo Clinic meta-analysis, the authors stated:

“Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.” [5]

But unfortunately, atrial fibrillation (AF) risk also appears to increase with dosage.

A separate meta-analysis found that:

• Marine Omega-3s increased AF risk by 25% overall
• At >1 g/day:
  
  • 49% increased risk (HR: 1.49; 95% CI: 1.04–2.15)
• At ≤1 g/day:
  • 12% increased risk (HR: 1.12; 95% CI: 1.03–1.22)
    
• P for interaction <0.001, indicating dose matters [12]

And the latest study in dialysis patients? They used 4 g/day [11].

In patients at such high risk of death, a small bump in atrial fibrillation is probably worth the trade-off. But for the rest of us, it may not be.

So here’s the approach I personally take.

I think the evidence of a protective effect for heart health with Omega-3 is compelling. But I also want to stay away from the higher doses that are linked with an elevated risk of atrial fibrillation.

So I take 1 g a day.

But of course, just because I’m taking a supplement, that doesn’t mean you need to. It’s a decision to be made based on your own risk factors and with your doctor.

References

1. https://pubmed.ncbi.nlm.nih.gov/16825676/


2. https://pubmed.ncbi.nlm.nih.gov/22686415/


3. https://jamanetwork.com/journals/jama/fullarticle/2773120


4. https://www.nejm.org/doi/full/10.1056/NEJMoa1811403


5. https://www.mayoclinicproceedings.org/article/S0025-6196%2820%2930985-X/fulltext


6. https://www.nejm.org/doi/full/10.1056/NEJMe2515057


7. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773162

8. https://pubmed.ncbi.nlm.nih.gov/26139229/


9. https://www.ahajournals.org/doi/10.1161/JAHA.123.032231


10. https://pubmed.ncbi.nlm.nih.gov/40840478/


11. https://www.nejm.org/doi/full/10.1056/NEJMoa2513032


12. https://pmc.ncbi.nlm.nih.gov/articles/PMC9109217/