Cardiac MRI Shows Post-MI Remodeling Gains From High-Dose Omega-3 Fatty Acids

Marlene Busko

August 03, 2016

BOSTON, MA — Half a year of treatment with a high dose of omega-3 acid ethyl ester (Lovaza, GlaxoSmithKline) in patients with a recent MI surpassed placebo in mitigating adverse cardiac remodeling[1].

The Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction (OMEGA-REMODEL) trial by Dr Bobak Heydari (Brigham and Women's Hospital, Boston, MA) and colleagues was published in the August 2, 2016 issue of Circulation. It was presented in preliminary form at a meeting last year and covered by heartwire from Medscape at the time.

The trial randomized 358 patients who had had a recent heart attack to receive placebo or 4 mg/day of Lovaza plus standard care for 6 months. Patients who received the study drug had a lower adverse left ventricular end systolic volume index (LVESVI; an indication of the heart's pumping ability), less myocardial scarring (fibrosis) in the undamaged areas of the heart, and better levels of some serum biomarkers.

On average, patients who received the fish-oil capsules experienced about a 6% improvement in heart pumping function and about a 6% suppression of fibrosis. However, patients whose red blood cell levels of omega-3 fatty acid were in the highest quartile had a 13% improvement in heart pumping function, suggesting a dose-response relationship. There were also no major adverse effects.

Even though survival in the first few months after a heart attack "has dramatically improved in the past decade," a fair number of patients develop heart failure, senior author Dr Raymond Y Kwong (Brigham and Women's Hospital, Boston, MA), told heartwire . "Drugs that potentially work along the line of suppressing inflammation . . . and improving remodeling after a heart attack are scarce," so it would be helpful to have more treatment options, he noted.

However, these are "intriguing" but preliminary findings, Kwong cautioned. "It is premature to advise heart-attack patients to consume 4 g of fish oil," which is far more than a person could obtain from eating fish, he noted. Although Lovaza and, since 2014, four generic omega-3 acid ethyl esters are approved by the US Food and Drug Administration for treating certain patients with high triglycerides, these drugs have not been approved to protect against cardiac remodeling in patients who have had an MI, and therefore, importantly, this use is not covered by insurance companies.

Effect of Fish-Oil Capsules to Heal the Heart

Preclinical trials have shown that omega-3 fatty acid has cardiovascular benefits, but two large clinical trials of fish oil in patients who have had an MI have had inconsistent findings. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione trial in Italy showed a reduction in mortality with omega-3 fatty-acid therapy, but the OMEGA trial in Germany did not show any beneficial effects; and both trials used a dose of 1 g daily.

Thus, Heydari et al used cardiac MRI to test the hypothesis that a larger, 4-g/day dose of omega-3 fatty acids given for 6 months would attenuate adverse left ventricular remodeling beyond standard care.

They randomized 358 patients within 14 to 28 days after they had an MI and were seen in three tertiary care centers in Boston. The patients received standard care plus either the study drug (about 465 mg of eicosapentaenoic acid [EPA] and about 375 mg of docosahexaenoic acid [DHA]) or a corn-oil placebo, taken as 4 capsules daily, with meals, for 6 months.

At baseline and at 6 months, the patients had cardiac MRI and blood tests to determine serum levels of markers of inflammation (C-reactive protein, myeloperoxidase, lipoprotein-associated phospholipase A2, fibrinogen), neurohormonal activation (N-terminal prohormone brain natriuretic peptide, cystatin C), and cardiac fibrosis (ST-2, galectin-3), as well as red blood cell levels of omega-3 fatty acid (which correlates with myocardial levels)

A total of 133 of 180 patients in the study drug group and 128 of 178 patients in the placebo group had data from both visits; about 40 patients in each group refused to come for the follow-up visit or had moved out of state.

In an intention-to-treat analysis, compared with patients who received placebo, those who received omega-3 fatty acids had significant reductions of left ventricular systolic volume index (–5.8%, P=0.017) and noninfarct myocardial fibrosis (–5.6%, P=0.026).

They also had a significant reduction of biomarkers of inflammation (myeloperoxidase, lipoprotein-associated phospholipase A2) and myocardial fibrosis (ST2).

"We therefore speculate that [omega-3 fatty-acid] treatment provides the . . . improvement in LV remodeling and noninfarct myocardial fibrosis through suppression of inflammation at both systemic and myocardial levels during the convalescent healing phase after acute MI," Heydari and colleagues write.

The drug was safe: the most common side effect was nausea, reported in 5.9% of the fish-oil–treated arm and 5.4% of the placebo arm (P=0.11). None of the fish-oil–treated patients had any significant bleeding related to the study drug, Kwong pointed out. There were three (2%) and eight (4%) deaths in placebo and fish-oil–treated patients, respectively (P=0.22).

These patients received optimal standard care, "yet the omega-3 fatty acids were able to provide an incremental benefit; we believe the findings were intriguing for those reasons," said Kwong.

"I think clinicians need to be aware of the potential promise of this line of therapy," he continued. "We are planning a larger clinical trial to see the outcome effects of fish oil in driving down heart failure," and there is also a need for more study of the downstream metabolites of this drug.

The study was funded by the National Institutes of Health, and the study drug and placebo were provided by GlaxoSmithKline. The authors have no relevant financial relationships.

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