Combined EPA and DHA supplementation showed no broad benefit for major adverse cardiovascular events in patients with established diseaseNew research shows combined fish oil supplements did not lower heart attack risk for patients with existing heart disease

Pharmacology research & perspectives Published June 1, 2026 Study authors: Shayan Sepideh Karkon, Abbood Rosull Saadoon, Al-Taie Sarah F, Nataj Paria Ganji, Khamdamjonovna Mak… PubMed ↗ DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Consider that combined moderate-dose EPA + DHA offers no broad benefit for MACE or AF risk in heterogeneous post-event populations.

This meta-analysis examined the impact of combined eicosapentaenoic acid and docosahexaenoic acid supplementation on patients with established cardiovascular disease. The study focused on secondary prevention or perioperative settings where patients received high background guideline-directed medical therapy. The primary outcome assessed was major adverse cardiovascular events, while secondary outcomes included atrial fibrillation and postoperative atrial fibrillation incidence.

The analysis revealed no significant reduction in major adverse cardiovascular events. While there was a trend toward reduced atrial fibrillation incidence, this did not reach statistical significance. The authors noted that the heterogeneous nature of the post-event populations likely contributed to the lack of broad benefit in reducing cardiovascular risk or atrial fibrillation risk.

Key limitations identified by the authors include moderate-dose combined supplementation use and limited subgroup reporting on metabolic comorbidities such as diabetes and hypertriglyceridemia. The presence of concomitant therapies like statins and high background medical therapy reduced residual risk, potentially masking any potential treatment effects. Consequently, the practice relevance is limited to specific contexts rather than offering broad clinical utility.

This big study looked at over 25,000 people who already had heart disease. They took a mix of two types of healthy fats found in fish oil. The goal was to see if these supplements could help prevent serious heart problems like heart attacks or strokes.

The main results showed no clear benefit for preventing major heart events. The data did not prove that taking these supplements made a difference in stopping bad heart outcomes for this group of patients.

There was a small sign that fewer people had irregular heartbeats, but this finding was not strong enough to be sure. The study also noted that many patients were already on other strong heart medicines, which might have made it hard to see extra benefits from the supplements.

Doctors should know that these fish oil supplements do not broadly lower the risk of heart attacks or irregular heartbeats for most patients with heart disease.

What this means for you:

Moderate-dose combined fish oil supplements did not lower major heart event risk for patients with existing heart disease.

Study Details

Study typeMeta analysis

Sample sizen = 578

EvidenceLevel 1

PublishedJun 2026

PMID42144851

View Original Abstract ↓

Cardiovascular diseases (CVD) remain to impose a main global burden of morbidity and mortality despite advances in anticipation and treatment. Omega-3 fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been extensively studied for potential cardioprotective effects, yet their impact on cardiovascular outcomes remains debated due to heterogeneity in formulation, dose, and patient subgroups. This meta-analysis evaluated the effects of EPA and DHA supplementation on major adverse cardiovascular events (MACE) and atrial fibrillation (AF), including postoperative AF (POAF), in patients with established CVD. A systematic search of Embase, PubMed/MEDLINE, Scopus, and Web of Science (January 2010-December 2021) identified randomized controlled trials (RCTs) of combined EPA + DHA supplementation in secondary prevention or perioperative settings. Data were synthesized using RevMan v5.3 with a random-effects model, and study quality was assessed via the Cochrane RoB 2 tool. From 3682 records, 25 RCTs (n = 25 578 patients) were included. Pooled analysis showed no significant reduction in MACE (effect estimate 0.042 ± 0.0499, Z = 0.850, 95% CI [-0.055, 0.140], p = 0.396; low heterogeneity) or AF/POAF incidence (trend toward reduction: -0.198 ± 0.1498, Z = -1.319, 95% CI [-0.491, 0.096], p = 0.187; modest heterogeneity). Neutral findings likely reflect moderate-dose combined EPA + DHA use, limited subgroup reporting on metabolic comorbidities (e.g., diabetes, hypertriglyceridemia) or concomitant therapies (e.g., statins), and high background guideline-directed medical therapy reducing residual risk. Although omega-3 fatty acids exert anti-inflammatory, antithrombotic, and lipid-modulating effects, this analysis indicates no broad benefit in reducing MACE or AF risk with combined moderate-dose EPA + DHA in heterogeneous post-event populations. Recent evidence highlights more MACE reductions with high-dose purified EPA monotherapy in high-metabolic-risk subgroups, balanced against dose-dependent AF increases at high doses (> 1.5 g/day). Future large-scale RCTs should prioritize biomarker-verified compliance, metabolic/concomitant therapy stratification, and formulation-specific comparisons to define targeted therapeutic roles. Trial Registration: This study has been registered in PROSPERO, and the registration code is 642795.

Combined EPA and DHA supplementation showed no broad benefit for major adverse cardiovascular events in patients with established diseaseNew research shows combined fish oil supplements did not lower heart attack risk for patients with existing heart disease

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Combined EPA and DHA supplementation showed no broad benefit for major adverse cardiovascular events in patients with established diseaseNew research shows combined fish oil supplements did not lower heart attack risk for patients with existing heart disease

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