Insulin Resistance Modifies the Effects of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction (from the OMEGA-REMODEL Randomized Clinical Trial)

Abstract

Insulin resistance early after acute myocardial infarction is associated with increased heart failure and mortality. OMEGA-REMODEL was a prospective double-blind 1:1 randomized control trial of patients with AMI. We reported that 6-month treatment with omega-3 fatty acid (O-3FA) 4 g/day attenuated cardiac remodeling accompanied by reduction in inflammation. We hypothesized that insulin resistance modifies the therapeutic effect of O-3FA on post-MI cardiac remodeling. The OMEGA-REMODEL study group was dichotomized according to cohort- and gender-specific median cutoff value of leptin-to-adiponectin ratio (LAR) at baseline (LAR-Hi vs LAR-Lo). Mixed model regression analyses were used to evaluate effect modification of O-3FA on reduction of left ventricular end-systolic volume index (LVESVI) by LAR status. Baseline LAR was evaluated on 325 patients (59 ± 11 years, 81% male). A total of 168 patients were categorized in LAR-Lo, and 157 in LAR-Hi. O-3FA treatment resulted in significant LVESVI reduction in patients with LAR-Lo but not with LAR-Hi (p = 0.0002 vs 0.66, respectively). Mixed model regression analysis showed significant modification of LAR on O-3FA's treatment effect in attenuating LVESVI (p = 0.021). In conclusion, this post-hoc efficacy analysis suggests that LAR status significantly modified O-3FA's treatment effect in attenuating cardiac remodeling. During the convalescent phase of acute infarct healing, patients with lower insulin resistance estimated by LAR appear to derive more therapeutic response from O-3FA toward improvement of LVESVI.

Trial registration: ClinicalTrials.gov NCT00729430.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1.

%change from baseline to follow-up in (A) LVESV and (B) ECV remote, comparing O-3FA treatment groug and placebo group. Significant change was observed in patients with LAR-Lo but not with LAR-Hi.

Figure 2.

The odds of improving (A) LVESVI and (B) ECVremote by O-3FA comparing patients high and low levels of LAR, proinsulin, C-peptide, and HOMA-IR. The odds of improving LVESVI and ECVremote was significant in LAR-Lo group but not significant in LAR-Hi group.

Figure 3.

The difference of LVESVI between baseline and follow-up in patients with (A) LAR-Lo and (B) LAR-Hi.