Melatonin for recovery after heart attack

reference

Dominguez-Rodriguez A, Abreu-Gonzalez P, de la Torre-Hernandez JM, et al. Early treatment with melatonin for reducing the infarction size in patients with myocardial infarction with ST-distance elevation who receive percutaneous coronary intervention (from the melatonin additive in the "Acute Myocardial Infarction Treated With Angioplasty"). am j cardiol . 2017; 120 (4): 522-526.

Study goal

It should be evaluated whether the treatment effect of high-dose melatonin therapy in patients with myocardial infarction with ST-distance elevation (Stemi) is influenced by time until administration in relation to the cardiac event.

draft

The authors carried out a post-hoc analysis of the melatonin additive in the Maria study (Acute Myocardial Infarction Treated with Angioplasty) (NCT00640094), in which stemi patients randomize melatonin (intravenous and intracorone bolus) or placebo during a primary percutaneous coronary intervention (PCI).

participant

The Maria study included 146 patients who introduced themselves with Stemi within 6 hours after the chest pain began. The participants were randomized and received intravenous and intracoronary melatonin (n = 73) or placebo (n = 73) during the primary PCI.

medication and dosage study

The participants of the Maria study received 12 mg melatonin intravenously as a continuous infusion for 60 minutes. This dose increases the melatonin blood level about 12,000 times higher than the highest night values. In addition, the patients received a bolus of 2 mg intracoronary melatonin, which was administered by the PCI guide catheter after the blood flow was restored to the artery connected to the infarction.

target parameter

The primary end of effectiveness of the original Maria study was determined whether the treatment with melatonin reduces the infarction size, which is determined by the cumulative release of alpha hydroxybutyrat dehydrogenase (area under the curve: 0 to 72 h). Secondary endpoints were clinical events that occurred within the first 90 days: death, persistent ventricular arrhythmias, resuscitation after cardiac arrest, cardiogenic shock, heart failure, severe bleeding, stroke, necessity of revascularization, recurrent ischemia, pure coloring and dehospitalization.

Last year there were strong indications that melatonin should have been useful.

The study checked here is a secondary post-hoc analysis of data from the Maria study. The authors divided the patients treated in the Maria study in 3 groups (tertile), based on the time between the start of symptoms and "balloon" (when the balloon is inflated to restore the river during the PCI):

• First tertil: 136 ± 23 minutes
• second tertil: 196 ± 19 minutes
• third tertil: 249 ± 41 minutes

You used statistical analyzes to assess the relationships between the treatment effect and time.

important knowledge

This is the second of 2 important publications from the Maria study on Melatonin and heart attacks this year. This study examined whether the treatment effect of melatonin therapy in patients with stemi is influenced by time until administration.

The original Maria study began in 2007 and was a monocentric, prospective, randomized, double-blind, placebo-controlled phase-2 study for intravenous administration of melatonin. The results of this study were published in January 2017.

The present analysis was published in August 2017 and examined the effect of the time until the melatonin gift at MIS. The information from these two studies is relevant.

The first publication of the Maria results in January showed little benefits of the melatonin debt. The Baseline characteristics between the groups were similar. The size of the myocardial infarction, which was determined within a week after the procedure, does not differ between the melatonin and placebo group ( p = 0.63). The infarction size 130 days after the primary PCI, carried out in 91 patients (72.8 %), showed no statistically significant differences between the groups ( p = 0.27). The restoration of the left ventricular volume and the ejection fraction (LVEF) of 6 to 130 days after the procedure did not differ significantly, although the placebo group tended to higher volumes (60.0 ± 10.4 % compared to 53.1 ± 12.5 %; p = 0.008). Both the left ventricular end diastolic and the end systolic volume were lower in the placebo group ( p = 0.01). The incidence of undesirable events after 1 year was comparable in both groups ( p = 0.150). Therefore, intravenous and intracoronary melatonin was not connected to a reduction in the infarction size in a non-limited stemi population and has an unfavorable effect on the ventricular volumes and the LVEF development. ²

In the patient in the first tertil, who underwent the procedure earlier after the start of the symptoms, the infarction size of the subjects treated with melatonin was significantly smaller compared to placebo (14.6 ± 14.2 vs. 24.9 ± 9.0 %; p = 0.003).

On the other hand, treatment with melatonin was connected to the patients included in the third tertil (20.5 ± 8.7 % vs. 11.2 ± 5.2 %; p = 0.001).

practice implications

Everyone would like to have a simple intervention that can be given to a patient during and after a heart attack that reduces the long -term damage and accelerates the recovery.

In these reviews, we generally report good news; The Maria study forms something like an exception to this rule. The intervention has brought no benefit to these patients, but to be honest it is not an intervention that a naturopath would consider - it is outside of our framework and certainly outside of our philosophy.

Last year there were strong indications that melatonin should have been useful. A study of June 2017 reported that melatonin relieves myocardial ischemia/reproachment injuries in rats. ^{3 It also suppresses the platelet activation, which is triggered by cardiac ischemia/reproachment violation. 4}

Maybe the Maria Melatonin dose was simply too high or too intense. Perhaps it reached the heart too late to be still useful.

A year ago, Javanamard et al. Of these patients, 10 mg of melatonin orally received 20 1 month before going to bed. The 19-member control group received placebo. The average concentrations of 3 markers of the endothelzell function, including the intercellular adhesion molecule (ICAM), the vascular cell adhesion molecule (VCAM) and the C reactive protein (CRP), showed statistically significant reductions in the melatoning group. There was a statistically significant decrease in serum nitrogen monoxide (NO) in the control group, but no change in the melatoning group. ⁵

That is confusing. We had hoped that the Maria study would provide a clear justification for using melatonin aggressive for use in patients with heart attacks or balloon processes in order to limit tissue damage and accelerate recovery. In this case, the timing makes a big difference; Early administration could still prove to be useful, but later treatment could backfire.

The Harvard researcher Eva Schernhammer reported in May 2017 that there is a significant reverse connection between melatonin secretion and the MI risk, with a lower melatonin secretion being significantly associated with a higher MI risk. The ODDS ratio (OR) for each sulfateoxymelatonin/creatinine ratio for each lower logarithmically transformed was 1.51 (95% confidence interval [CI]: 1.16-1.96). Women in the highest category had an estimated absolute MI risk of 84 cases per 100,000 people in the lowest category compared to 197 cases per 100,000 people. The association was strongly modified by the BMI (P-value for interaction = 0.02). ⁶

In a study from 2014 on sub-body memia and reperfusion during the repair of the abdominal aorta, a 50 mg dose of melatonin plus a postoperative dose of 30 mg oxidative stress and myocardial damage. ⁷

It is clear that melatonin can be helpful, we probably only need the right dose at the right time. We're not there yet.