Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction

Abstract

BACKGROUND Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects but their role in modifying cardiac structures and tissue characteristics in patients who have suffered an acute myocardial infarction (MI) while receiving current guideline-based therapy remains unknown. METHODS In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute MI were randomized 1:1 to 6-months of high-dose omega-3 fatty acids (n=178) or placebo (n=180). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and following study therapy. The primary study endpoint was change in left ventricular systolic volume index (LVESVI). Secondary endpoints included change in non-infarct myocardial fibrosis, LVEF, and infarct size. RESULTS By intention-to-treat analysis, patients randomized to omega-3 fatty acids experienced a significant reduction of LVESVI (−5.8%, P=0.017), and non-infarct myocardial fibrosis (−5.6%, P=0.026) compared with placebo. Per-protocol analysis revealed that those subjects who achieved the highest quartile increase in RBC omega-3 index experienced a 13% reduction in LVESVI as compared with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. CONCLUSIONS Treatment of acute MI patients with high-dose omega-3 fatty acids was associated with reduction of adverse LV remodeling, non-infarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.

Polyunsaturated fatty acids supplementation impairs anti‐oxidant high‐density lipoprotein function in heart failure

“…In the light of previous reports showing that treatment with n3‐PUFAs improves left ventricular function in HF by reducing ventricular remodelling and myocardial fibrosis,8, 11 our finding is rather surprising at first. However, upon a closer look, this result may provide preliminary evidence for a mechanistic link for previous conflicting study results 13.…”

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

“…In a recent study, EPA and DHA have been shown to reduce myocardial fibrosis. EPA and DHA supplementation for 6 months in post–myocardial infarction patients was associated with a favorable effect on left ventricular remodeling and a significant reduction in noninfarct myocardial fibrosis measured by cardiac magnetic resonance imaging (mean reduction, −5.6%; 95% CI, −10.4% to −0.9%; P =0.022) compared with placebo 35. In a subset of 6 patients from the current study, several resolvins, which have been shown to be present in healthy subjects,36, 37, 38 were absent or present at low levels in CAD patients not on omega‐3 ethyl‐ester; the resolvins were restored or their level increased in those receiving omega‐3 ethyl‐ester 39.…”

Response by Heydari et al to Letter Regarding Article, “Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial”

“…1 Dr. Naegele expressed concern regarding the safety of omega-3 fatty acids based on the numbers of mortality cases in the omega-3 fatty acid and placebo treatment arms. Dr. Naegele postulated that the long term cumulative effect of omega-3 fatty acids exposure may be harmful due to “lipid peroxidation” following “gradual accumulation within biological membranes.” Although, at the present time, the effects of omega-3 fatty acids on lipid peroxidation and mitochondrial glucose utilization remain unclear, 2 we do not find supportive evidence that indicate harmful effects from omega-3 fatty acids in our study.…”

“…1 This was in part complicated by the heterogeneity in study methods and target patient populations in the medical literature. Our study results demonstrated substantial reductions in adverse left ventricular (LV) remodeling, non-infarct myocardial fibrosis, and circulating biomarkers of inflammation in those patients who achieved a substantial increase in RBC omega-3 fatty acid levels.…”

“…Our study results demonstrated substantial reductions in adverse left ventricular (LV) remodeling, non-infarct myocardial fibrosis, and circulating biomarkers of inflammation in those patients who achieved a substantial increase in RBC omega-3 fatty acid levels. 1 Interestingly, a recent meta-analysis inclusive of studies that measured circulating or tissue omega-3 fatty acid levels within 45,637 patients associated omega-3 fatty acids use with a significant decreased risk of cardiovascular mortality. 3 …”