Omega-3 Fatty Acids Protect Against Cardiac Remodeling and Fibrosis Following MI: OMEGA-REMODEL

March 06, 2015

SAN DIEGO, CA — Patients with MI treated with a high-dose of omega-3 fatty acids on top of standard care had significant improvements in cardiac function and structure compared with individuals who received standard medical care alone, according to the results of a new study[1].

Among those who received a daily 4-g dose of omega-3 fatty acids (Lovaza, GlaxoSmithKline), MRI revealed a significant reduction in the left ventricular end systolic volume index (LVESVI) and myocardial extracellular volume fraction (MECVF), report investigators.

"The high-risk post-MI period is one of the remaining battles for physicians," senior investigator Dr Raymond Kwong (Brigham and Women's Hospital, Boston, MA) told heartwire . "In spite of all of our therapies, while mortality rates have improved a lot, certain outcomes, such as arrhythmias or sudden death, remain fairly high. We were interested in whether omega-3 fatty acids could favorably change ventricular remodeling, if they could change the way the heart contracts, and also what they could do to the region of the myocardium that was not infarcted. MRI was the right tool for that."

Scheduled for presentation next week at the American College of Cardiology 2015 Scientific Sessions in San Diego, CA, the study, known as the OMEGA-REMODEL trial, included 358 post-MI patients randomized to omega-3 fatty-acid supplementation or to matching placebo. The trial was designed years back following the positive GISSI-Prevenzione study, a landmark trial that showed the benefit of a 1-g dose of omega-3 fatty acids on the incidence of sudden death and all-cause mortality. Subsequent studies, noted Kwong, have not shown a similar benefit, however.

"If you take a step back and look at the basic pharmacokinetics and the reported mechanisms of fish oil, there are a number things favorable to cardiac health," said Kwong. Some of the beneficial aspects of fish oil include pleiotropic effects, such as the ability to reduce inflammation, which would be favorable in the post-MI setting.

In OMEGA-REMODEL, 6 months of treatment with the polyunsaturated fatty acid resulted in a significant reduction in LVESVI, a marker associated with improved prognosis following MI, compared with the placebo-treated patients. The researchers also examined the area of heart muscle undamaged by the infarction, which is measured using MECVF, a relatively new metric. This fraction is an estimation of how much fibrosis occurs following MI.

"The idea is that after a heart attack, the undamaged heart muscle may develop fibrosis because the heart is now weaker and the rest of heart muscle has to work harder to contract," said Kwong. "If there is ongoing inflammation induced by the heart attack, then this inflammation might cause some degree of fibrosis in the 'good' muscle. We wondered if this process was altered by the fish oil. We found that patients who received the fish oil did have a substantial reduction in the extracellular volume fraction."

There was also a significant reduction in inflammatory biomarkers such as C-reactive protein (CRP) and myeloperoxidase, as well as reduction in ST2, which is a marker of the severity of adverse cardiac remodeling and fibrosis, according to the group.

Given the surrogate outcomes in this trial, Kwong said they have proposed a larger randomized, controlled clinical trial investigating the effect of high-dose omega-3 fatty acids on hard end points in patients who have had an MI. They are continuing to study the present group and collect data on clinical events, but the present trial, which is large for a remodeling study, is underpowered to determine effects on cardiovascular end points. Given the improvements in MECVF and LVESVI, though, it is conceivable these changes would lead to better outcomes, said Kwong.

GlaxoSmithKline provided the omega-3 fatty acids used in the trial.


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