Early Treatment of Acute Myocardial Infarction with Melatonin: Effects on MMP-9 and Adverse Cardiac Events

Abstract

Background: Matrix metalloproteinase-9 (MMP-9) is crucial in tissue remodeling after an adverse cardiac event. In experimental studies, melatonin has been found to attenuate MMP-9 activation. The present study assessed the effects of systemic melatonin administration on the prognosis of patients with acute myocardial infarction (AMI) successfully treated with primary percutaneous coronary intervention, and to examine the effects on MMP-9 levels. Methods: We conducted a randomized controlled trial, enrolling patients who underwent primary percutaneous coronary intervention due to AMI. They were assigned to two groups for melatonin or placebo. The primary endpoint was a combined event of mortality and heart failure readmission at 2 years. The secondary endpoint was the levels of MMP-9 after the percutaneous coronary intervention. Results: Ninety-four patients were enrolled, 45 in the melatonin group and 49 in the control group. At 2 years of follow-up, 13 (13.8%) patients suffered the primary endpoint (3 deaths and 10 readmissions due to heart failure), 3 patients in the melatonin group and 10 in the placebo group. The difference in the restricted mean survival time was 87.5 days (p = 0.02); HR = 0.3 (95% CI 0.08–1.08; p = 0.06); Log-rank test 0.04. After controlling for confounding variables, melatonin administration reduced MMP-9 levels to 90 ng/mL (95% CI 77.3–102.6). Conclusions: This pilot study demonstrated that compared to placebo, melatonin administration was associated with better outcomes in AMI patients undergoing primary percutaneous coronary intervention.

Traumatic Brain Injury, Sleep, and Melatonin—Intrinsic Changes with Therapeutic Potential

“…Researchers found that melatonin was associated with a significant reduction in infarct size when given early after symptom onset [ 50 ]. A follow-up pilot RCT showed increased survival rates among melatonin recipients as measured by mortality and heart failure readmission at two years [ 51 ]. Interestingly, in the short term, there was no improvement in myocardial salvage index on cardiac MRI at day 4 (+/−1) after intravenous melatonin administration following STEMI.…”

The role of the circadian system in cardiovascular diseases and clinical implications

“…U prospektivnoj, randomizovanoj studiji Domínguez-Rodríguez i saradnici su pokazali da je intravenska primena melatonina kod bolesnika sa STEMI, lečenih primarnom perkutanom koronarnom intervencijom, korelirala sa redukcijom mortaliteta i rehospitalizacije zbog srčane slabosti, u dvogodišnjem periodu praćenja. Efekat melatonina se ogledao u atenuaciji matriksne metaloproteinaze-9, ključnog enzima uključenog u remodelovanje miokarda usled akutnog infarkta miokarda (36). Studija publikovana u Lancet-u 2018. godine pokazala je značaj hronobiologije i u kardiohirurgiji.…”

“…In a prospective randomized study, Domínguez-Rodríguez et al showed that intravenous administration of melatonin in patients with STEMI treated by primary percutaneous coronary intervention correlated with a reduction in mortality and rehospitalization due to heart failure in a two-year follow-up period. The effect of melatonin was reflected in the attenuation of matrix metalloproteinase-9, a key enzyme involved in myocardial remodeling due to acute myocardial infarction (36). A study published in Lancet in 2018 showed the importance of chronobiology in cardiac surgery.…”