Fish Oil and Heart Attacks and Strokes: What VITAL, REDUCE-IT, STRENGTH and ASCEND Found
Trial by trial, what VITAL, ASCEND, REDUCE-IT and STRENGTH found for omega-3 and heart attacks and strokes, plus what pooled reviews say, and why the products differ.
Content last updated . This page has not been medically reviewed.
Quick answer
Large trials of omega-3 for heart attacks and strokes do not agree, and the reason is partly that they tested different products in different people. Two trials of ordinary 1-gram capsules in people without known heart disease (VITAL and ASCEND) did not find a significant drop in their main outcome. A trial of a purified prescription EPA product (REDUCE-IT) did, and a trial of a prescription EPA and DHA product (STRENGTH) did not. None of these results can simply be carried over to a different product, amount or group. All amounts are study amounts, not advice.
What a "cardiovascular event" means
A major cardiovascular event is usually a combined outcome of heart attack, stroke or death from cardiovascular causes. Some trials add procedures such as coronary revascularization, or hospital admission for unstable angina. The outcomes differ between trials, so compare the rows below with care. A change in cholesterol or triglycerides is a lab biomarker, not a heart attack.The four named trials
| Trial | Who, how long | Product and comparator | Main result |
|---|---|---|---|
| VITAL | 25,871 US adults (men 50+, women 55+), no prior heart disease; median 5.3 years | 1 g a day marine omega-3 vs placebo (also tested vitamin D) | Major cardiovascular events: hazard ratio 0.92 (95% CI 0.80 to 1.06), not significant. [1] |
| ASCEND | 15,480 adults with diabetes and no evident cardiovascular disease; mean 7.4 years | 1-g capsules of omega-3 vs olive oil placebo daily | Serious vascular events 8.9% vs 9.2% (rate ratio 0.97, 95% CI 0.87 to 1.08). [2] |
| REDUCE-IT | 8,179 statin-treated adults with triglycerides 135 to 499 mg/dL and cardiovascular disease, or diabetes plus risk factors; median 4.9 years | 4 g a day icosapent ethyl (purified EPA ethyl ester, prescription) vs placebo | Primary events 17.2% vs 22.0% (hazard ratio 0.75, 95% CI 0.68 to 0.83). Funded by the manufacturer. [3] |
| STRENGTH | 13,078 statin-treated adults at high risk with raised triglycerides and low HDL cholesterol | 4 g a day EPA and DHA carboxylic acid (prescription-type) vs corn oil | Primary events 12.0% vs 12.2% (hazard ratio 0.99, 95% CI 0.90 to 1.09). Stopped early for low probability of benefit. [4] |
Other details worth knowing.
- In VITAL, total heart attack was lower (hazard ratio 0.72, 95% CI 0.59 to 0.90) in a secondary analysis, while stroke (1.04) and cardiovascular death (0.96) were not. The paper reported no excess risk of bleeding or other serious adverse events. [1] A secondary result is a hint to test, not a finding on its own.
- In REDUCE-IT, hospitalization for atrial fibrillation or flutter was 3.1% vs 2.1%, and serious bleeding was 2.7% vs 2.1% (P=0.06). [3]
- In STRENGTH, stomach side effects were 24.7% with the omega-3 product vs 14.7% with corn oil. [4]
- The sources we read do not explain why REDUCE-IT and STRENGTH differed. The product (EPA alone vs EPA and DHA), the form, the placebo or comparator, and the study populations were not the same.
Pooled reviews
| Review | What it combined | What it found |
|---|---|---|
| Cochrane 2020 | 86 trials, 162,796 adults; fish and plant omega-3, mainly capsules | Little or no effect on all-cause death (RR 0.97, high certainty), cardiovascular events (RR 0.96, high certainty) or stroke (RR 1.02, moderate certainty). Possible slight reduction in coronary heart disease events (RR 0.91) and deaths (RR 0.90), low certainty. Effects did not differ by dose. [5] |
| Aung 2018 | 10 large trials, 77,917 high-risk people; EPA 226 to 1,800 mg a day; mean 4.4 years | No significant link with coronary heart disease death (RR 0.93), non-fatal heart attack (RR 0.97) or major vascular events (RR 0.97). [6] |
| Hu 2019 | 13 trials, 127,477 people; mean 5.0 years | Lower risk of heart attack (RR 0.92), coronary death (RR 0.92) and total cardiovascular disease (RR 0.97) even after excluding REDUCE-IT; the authors reported a linear relationship with omega-3 dose. [7] |
The three reviews reach different headlines because they include different trials and analysis choices. Hu 2019 included REDUCE-IT in its analyses, and NCCIH says it added VITAL, ASCEND and REDUCE-IT to the earlier 10-trial review. [7][8] NCCIH's summary of this research says there is some evidence that people with heart disease or high triglycerides may benefit, and describes the 2020 Cochrane finding as a slight reduction in coronary events and coronary death. [8]
What health bodies say
The NHS advises at least 2 portions of fish a week, including 1 of oily fish, and says long-chain omega-3 may help prevent heart disease. [9] MedlinePlus says certain fish are the best sources of omega-3 and cites the American Heart Association advice of at least 2 servings a week of omega-3-rich fish. [10] These are food-based statements and are not trial results for capsules. For the American Heart Association view on triglycerides, see omega-3 and high triglycerides. Cochrane notes there is little evidence from trials on the effects of eating fish. [5] Trial evidence for fish meals is therefore thin; see omega-3 supplements vs eating fish.Frequently asked questions
Does fish oil prevent heart attacks and strokes?
In VITAL and ASCEND, 1-g omega-3 capsules did not significantly lower the main outcome of major cardiovascular events compared with placebo. [1][2] Cochrane found little or no effect on overall cardiovascular events or stroke. [5]
Why did REDUCE-IT show a benefit and STRENGTH did not?
They tested different prescription products, EPA alone vs EPA and DHA, against different comparators in somewhat different high-risk groups. [3][4] The sources we read do not settle the reason.
Can I take over-the-counter fish oil to get the REDUCE-IT result?
REDUCE-IT tested a purified prescription EPA product at 4 g a day. NCCIH says prescription products may not have the same effects as dietary supplements. [8] Ask your prescriber before changing anything.
What did the pooled reviews find?
They differ. Cochrane found a possible slight reduction in coronary events, low certainty. Aung 2018 found no significant link. Hu 2019 found lower risk of heart attack and coronary death. [5][6][7]
Is eating fish different from taking capsules?
Yes. Trials of capsules do not test fish meals. The NHS advises oily fish as part of a balanced diet. [9]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Limits and uncertainty
- Trials differ in omega-3 type, form, amount, duration, comparator and participants; the comparison oil differs between trials (placebo, olive oil, corn oil), so "vs placebo" does not mean the same thing every time.
- Most trials were in adults in high-income countries. [5]
- Everyone in REDUCE-IT and STRENGTH was taking a statin, so those results may not apply to people who are not. [3][4]
- Lab changes (triglycerides, omega-3 index) are not heart attacks. See the omega-3 index and heart risk.
- Why trial results differ: why omega-3 trials disagree.
Safety and who should ask a clinician
Omega-3 products can interact with medicines that affect bleeding, and a prescription EPA label lists atrial fibrillation and bleeding warnings. [11] If you have heart disease, diabetes or take a blood thinner, ask your doctor or pharmacist before adding fish oil, and do not stop a prescribed medicine on your own. Tell your surgical team about any omega-3 product before an operation. Chest pain, shortness of breath, or signs of stroke need emergency care: call 911 in the US. See blood-pressure and cholesterol effects, fish oil and atrial fibrillation, after a heart attack and medication interactions.
References
- Manson JE et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer (VITAL). N Engl J Med 2019. Read 2026-10-23.
- ASCEND Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med 2018. Read 2026-10-23.
- Bhatt DL et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (REDUCE-IT). N Engl J Med 2019. Read 2026-10-23.
- Nicholls SJ et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk (STRENGTH). JAMA 2020. Read 2026-10-23.
- Abdelhamid AS et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020. Read 2026-10-23.
- Aung T et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials. JAMA Cardiol 2018. Read 2026-10-23.
- Hu Y, Hu FB, Manson JE. Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials. J Am Heart Assoc 2019. Read 2026-10-23.
- NCCIH, Omega-3 Supplements: What You Need To Know. Read 2026-10-23.
- NHS, Fish and shellfish. Read 2026-10-23.
- MedlinePlus, Omega-3 fats - Good for your heart. Read 2026-10-23.
- FDA-approved prescribing information for icosapent ethyl capsules (Vascepa), label revised 3/2026, DailyMed. Read 2026-10-23.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.