Melatonin as a cardioprotective therapy following ST-segment elevation myocardial infarction: is it really promising? Reply

We thank Dominguez-Rodriguez and Abreu-Gonzalez¹ for their comment on our ESC Working Group (WG) Position Paper on cardioprotection,² in which they propose melatonin to be a promising cardioprotective strategy. This was based, in part, on the recently published results of the Melatonin Adjunct in acute myocaRdial Infarction treated with Angioplasty (MARIA) trial, in which they investigated the cardioprotective effects of melatonin in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI).³ However, in the MARIA trial, the authors found that intravenous and intracoronary melatonin administered at the time of reperfusion failed to reduce acute myocardial infarct (MI) size (assessed by cardiac MRI).³ In fact, in that study, melatonin was found to actually worsen adverse post-MI left ventricular (LV) remodelling when compared to placebo (with significantly higher left LV end diastolic and systolic volumes, and lower ejection fraction on cardiac MRI at 4 months following PPCI).³ The cause of this detrimental effect of melatonin on post-MI LV remodelling is not clear, but may be related to its reported effects on increasing myocardial accumulation of collagen and glycosaminoglycans following infarction.⁴ In another study, oral melatonin started on the night following PPCI and continued daily during the hospitalisation, had mixed results on enzymatic MI size following STEMI (CK-MB and hs-Troponin-T at 6 h post-PPCI),⁵ although the study was underpowered (only 40 patients), and the dosing regimen was suboptimal. Another clinical study reported cardioprotective effects with 5 days' pre-treatment with melatonin in patients undergoing coronary artery bypass graft (CABG) surgery, as evidenced by less peri-operative myocardial injury when compared to placebo pre-treatment,⁶ suggesting that melatonin may be more effective as a cardioprotective agent when administered prior to index ischaemia (as in CABG surgery) rather than at the time of reperfusion (as in STEMI patients).

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