The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial

Abstract

Endothelial dysfunction (ED) precedes acute coronary syndrome. Oxidative stress results in ED but is reversible. Melatonin is aside from being a circadian hormone, also an antioxidant. The aim of this study was to investigate whether 25 mg melatonin administered for twelve weeks following acute coronary syndrome (ACS) could improve ED. In this placebo‐controlled randomized trial, ED was measured as reactive hyperemia index (RHI) at baseline, day 14, and day 84. The effect was assessed using a generalized estimating equation adjusted for the baseline RHI. As secondary outcome, the concentrations of three biomarkers were measured: l‐arginine, asymmetric dimethylarginine, and uric acid. Thirty‐one patients were included in the study. The intention‐to‐treat analysis of the primary outcome had 26 patients due to missing data. The estimated marginal mean difference in RHI at day 14 and day 84 between the groups was 0.15 (95% CI: 0.29‐0.01, P = .039) in favor of the placebo group. No significant differences in the biomarker concentrations were found. Melatonin treatment after ACS did not improve but may have aggravated ED. The significant difference between groups was in favor of placebo, but this might be due to the effect of missing data or uneven distribution of comorbidities.

Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized, double‐blinded clinical trial

“…In another study, while melatonin regulated some markers of ED in vitro and its high dose of 10 mg sustained‐release tablets, three times daily, had clinical benefit in early onset preeclampsia, but it did not affect endothelial function or oxidative stress markers in studied patients 23 . Our results are also in contrast to a recent study, which demonstrated that 12 weeks of 25 mg oral melatonin did not improve endothelial function, measured by reactive hyperemia index, or its serum markers in patients after acute coronary syndrome 24 …”

“… 23 Our results are also in contrast to a recent study, which demonstrated that 12 weeks of 25 mg oral melatonin did not improve endothelial function, measured by reactive hyperemia index, or its serum markers in patients after acute coronary syndrome. 24 …”

Sphingosine kinase 1 promotes cerebral ischemia‐reperfusion injury through inducing ER stress and activating the NF‐κB signaling pathway

“…Acute inflammation response has been regarded as a signal to clear the damaged tissue whereas chronic inflammation reaction seems to be a process related to tissue repairing (Cao et al, 2019;Eiringhaus et al, 2019). In our study, we found that the levels of acute and chronic inflammation response were significantly elevated by oxidative stress and (Oliveira et al, 2019;Zahid et al, 2019).…”

Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits

“…Pretreatment with melatonin during five days before coronary artery bypass grafting surgery reduced myocardial injury, heart rate, oxidative stress, and inflammatory markers when compared to placebo [ 240 ]. On the other hand, 25 mg melatonin administered for twelve weeks following acute coronary syndrome may aggravate endothelial dysfunction [ 241 ]. Interestingly, the combination of 50 mg intravenously and 10 mg orally display cardioprotection in patients undergoing abdominal aortic aneurysm repair, with a risk reduction of 25% of cardiac morbidity, including postoperative atrial fibrillation [ 242 ].…”