A type of omega-3 fatty acid found in oily fish, used as a medication to lower triglycerides, may directly protect the heart after a heart attack. A study led by the Research Institute of Sant Pau (IR Sant Pau) shows that the eicosapentaenoic acid ethyl ester (EPA-E) reduces cardiac damage through mechanisms that go beyond its effect on blood lipids. The study, published in the journal European Heart Journal, shows that this compound not only improves the lipid profile but also acts directly on injured cardiac tissue, modulating key processes such as inflammation, cellular metabolism, and oxidative stress. All of which are critical in the progression of myocardial infarction.
These findings are consistent with those observed in previous clinical trials, such as the REDUCE-IT study, in which this type of treatment was shown to reduce cardiovascular events in patients with hypertriglyceridemia—a common condition affecting nearly one-third of the population and associated with increased cardiovascular risk even in individuals with controlled LDL cholesterol levels—although the extent of this benefit cannot be explained solely by the reduction in circulating triglycerides.
“Until now, we knew this treatment helped reduce cardiovascular risk, but our results indicate that its effect is much broader. It acts directly on the infarcted heart, promoting mechanisms that limit injury and improve tissue response after a heart attack,” explains Dr. Gemma Vilahur, head of the Molecular Pathology and Therapeutics of Atherothrombotic Diseases research group at IR Sant Pau and of the group at the Biomedical Research Networking Center for Cardiovascular Diseases (CIBERCV), and senior author of the study.
The research, whose first author is PhD candidate Sebastià Alcover, provides a new perspective on the role of these compounds in cardiovascular protection by demonstrating that their benefit is not limited to triglyceride control, but also involves direct mechanisms acting on cardiac tissue that influence heart attack progression.
The study was conducted in an experimental rat model reproducing a common clinical situation, namely elevated blood triglyceride levels associated with a higher risk of myocardial infarction. To achieve this, researchers induced elevated triglyceride levels through a high-carbohydrate diet over several weeks and, once this metabolic alteration had been established, administered EPA-E to some animals for two weeks, while the remaining animals received no treatment.
After this period, the researchers induced a controlled myocardial infarction through temporary occlusion of a coronary artery and analyzed the progression of cardiac damage during the following 24 hours. This approach made it possible to study under controlled conditions both the effect of the treatment and the response of cardiac tissue after the heart attack.
The data obtained showed that treated animals had a significantly smaller infarct size than untreated animals, reflecting less extensive cardiac tissue damage. In addition, infarction-associated mortality was reduced by nearly half in treated animals (29%) compared with untreated animals (56%), approaching the values observed in the control group (13%), although the difference did not reach statistical significance.
One of the study’s most relevant findings was that these benefits were not associated with blood triglyceride levels. In fact, no association was observed between triglyceride concentration and the extent of cardiac damage or survival after myocardial infarction. This suggests that the reduction in damage does not depend exclusively on lowering these lipids, but rather that the treatment exerts additional effects directly on the heart.
“This result is important because it helps explain why this treatment has shown benefits in patients even when triglyceride levels are not particularly high,” says Sebastià Alcover. This finding challenges the idea that triglyceride reduction is the main mechanism underlying the treatment’s benefit and reinforces the hypothesis that EPA-E exerts a direct protective effect on cardiac tissue.
Beyond reducing initial injury, the study indicates that EPA-E intervenes in the processes that determine how the heart responds and repairs itself after a heart attack. Following interruption of blood flow, cardiac tissue enters a critical phase characterized by cell death, lipid accumulation, and an intense inflammatory response that, if disproportionate, may worsen injury.
Researchers observed that the treatment reduced lipid accumulation in cardiac tissue and limited cardiomyocyte death, two factors directly involved in the extent of damage. They also found lower activation of the processes leading to fibrosis, suggesting better preservation of heart structure after myocardial infarction.
Tissue analysis also showed a significant reduction in inflammatory cell infiltration, close to 50%, together with an increase in multiple signals associated with inflammation resolution. This shift indicates that the treatment not only attenuates the initial inflammatory response, but also promotes a faster transition toward repair phases.
“The heart not only suffers less damage, but also responds differently. We see a more controlled inflammatory response that is better directed toward repair, which likely contributes to limiting the long-term consequences of myocardial infarction,” explains Sebastià Alcover. Taken together, these findings reinforce the idea that the treatment modifies the way the heart responds to a heart attack, promoting more effective tissue recovery.
The study also identified relevant effects at the cellular and metabolic levels that help explain how the treatment protects the heart beyond the initial injury. After a heart attack, cardiac cells experience impaired energy production capacity, favoring the accumulation of stress-associated metabolites and worsening cardiac tissue injury.
In this regard, researchers observed that the treatment helped preserve mitochondrial function, the structures responsible for generating cellular energy, and reduced oxidative stress, one of the main mechanisms of damage following an ischemic event. In addition, metabolic analysis showed changes consistent with more efficient energy use by injured cardiac tissue.
The study also demonstrated remodeling of the heart’s lipid profile, with an increase in compounds associated with protective effects and a reduction in others linked to inflammation and cellular damage. This effect may be related, among other factors, to the compound’s ability to incorporate into cardiac cell membranes and displace lipids with greater pro-inflammatory potential.
“These results indicate that the treatment not only acts on the visible injury caused by the heart attack, but also on the internal functioning of cells, improving their ability to adapt to damage,” says Dr. Gemma Vilahur.
These findings help explain why the treatment maintains its protective effect even when triglyceride changes alone do not account for the observed improvement. By acting on energy production, lipid balance, and the cellular stress response, EPA-E helps cardiac tissue better tolerate oxygen deprivation and limit heart attack-associated damage, promoting more efficient recovery.
The study’s findings provide a mechanistic basis that helps explain why the treatment has shown benefits in previous clinical trials, even when triglyceride reduction does not fully explain the magnitude of the observed effect. In this regard, the work suggests that its clinical impact may largely depend on its ability to act directly on cardiac tissue and modify the heart’s response to myocardial infarction.
Although these findings will need to be confirmed in human clinical studies, the study proposes a shift in the approach to cardiovascular prevention by proposing that the benefit of these therapies may not be limited to controlling risk factors, but may also involve their ability to reduce damage once a heart attack has already occurred and improve cardiac tissue recovery.
Alcover S, Ramos-Regalado L, Muñoz-García N, Girón GO, Otero S, López S, Padro T, Badimon L, Vilahur G. Eicosapentaenoic acid ethyl ester, cardiac metabolomic and lipidomic signatures, and cardioprotection in myocardial infarction. Eur Heart J. 2026. https://doi.org/10.1093/eurheartj/ehag187
Last update: 27 de May de 2026
