Discrepancy Between Fasting Flow-Mediated Dilation and Parameter of Lipids in Blood: A Randomized Exploratory Study of the Effect of Omega-3 Fatty Acid Ethyl Esters on Vascular Endothelial Function in Patients With Hyperlipidemia

Introduction Omega-3 fatty acid ethyl esters (omega-3), an eicosapentaenoic acid and docosahexaenoic acid preparation (Lotriga®, Takeda Pharmaceutical Company Limited), are approved in Japan to treat triglyceridemia. We investigated the effects of omega-3 on vascular endothelial function, measured by flow-mediated dilation (FMD). Methods Patients with dyslipidemia receiving 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors were randomized 1:1 to receive omega-3 at 2 g (QD) or 4 g (2 g BID) for 8 weeks. The primary end point was the change from baseline of fasting %FMD in each treatment group. Secondary end points included the 4-h postprandial %FMD and 4-h postprandial triglyceride (TG) level. Results Thirty-seven patients were randomized to receive omega-3 at 2 g (n = 18) or 4 g (n = 19). Mean fasting %FMD did not increase from baseline to week 8 in the 2-g group (− 1.2%) or 4-g group (− 1.3%). Mean 4-h postprandial %FMD did not change from baseline to week 8 in the 2-g group (0.0%), but increased in the 4-g group (1.0%). Mean 4-h postprandial TG level decreased by 34.7 mg/dl from baseline over week 8 in the 2-g group, with a significantly larger decrease in the 4-g group of 75.9 mg/dl (p < 0.001). No new safety concerns were identified. Conclusions Fasting %FMD did not improve after 8 weeks of omega-3 treatment at 2 g or 4 g. After 8 weeks, 4-h postprandial TG levels showed improvement at both doses, with a greater reduction in the 4-g group. Trial Registration ClinicalTrials.gov, ID: NCT02824432.