Intra-coronary morphine versus placebo in the treatment of acute ST-segment elevation myocardial infarction: the MIAMI randomized controlled trial

Abstract

BackgroundExperimental studies suggest that morphine may protect the myocardium against ischemia-reperfusion injury by activating salvage kinase pathways. The objective of this two-center, randomized, double-blind, controlled trial was to assess potential cardioprotective effects of intra-coronary morphine in patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous intervention.MethodsNinety-one patients with STEMI were randomly assigned to intracoronary morphine (1 mg) or placebo at reperfusion of the culprit coronary artery. The primary endpoint was infarct size/left ventricular mass ratio assessed by magnetic resonance imaging on day 3–5. Secondary endpoints included the areas under the curve (AUC) for troponin T and creatine kinase over three days, left ventricular ejection fraction assessed by echocardiography on days 1 and 6, and clinical outcomes.ResultsInfarct size/left ventricular mass ratio was not significantly reduced by intracoronary morphine compared to placebo (27.2% ± 15.0% vs. 30.5% ± 10.6%, respectively, p = 0.28). Troponin T and creatine kinase AUCs were similar in the two groups. Morphine did not improve left ventricular ejection fraction on day 1 (49.7 ± 10.3% vs. 49.3 ± 9.3% with placebo, p = 0.84) or day 6 (48.5 ± 10.2% vs. 49.0 ± 8.5% with placebo, p = 0.86). The number of major adverse cardiac events, including stent thrombosis, during the one-year follow-up was similar in the two groups.ConclusionsIntracoronary morphine at reperfusion did not significantly reduce infarct size or improve left ventricular systolic function in patients with STEMI. Presence of comorbidities in some patients may contribute to explain these results.Trial registrationClinicalTrials.gov, NCT01186445 (date of registration: August 23, 2010).

Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury

“…However, the reality of the synergistic role of various biological mechanisms in IRI made it challenging to prevent or treat. Indeed, some medications with predicted benefits to IRI have not been proved with a definite role in prevention or treatment, likely vitamin C (Hill et al, 2019 ), morphine (Le Corvoisier et al, 2018 ), etc. In the field of liver transplantation, nearly all randomized clinical trials have ultimately failed to ameliorate liver IRI in patients (Zhai et al, 2013 ).…”

Sodium Thiosulfate in Acute Myocardial Infarction

“…Based on experience from local and previous studies, we allowed for up to a 33% dropout for the primary endpoint caused by contraindications for CMR—eg, implantable cardioverter-defibrillator implantation, claustrophobia, or unable to obtain sufficient image quality for infarct size detection. 36 , 37 , 38 , 39 Therefore, we expected to need to include 380 patients to obtain a reliable primary outcome measure in 250 patients. Due to the COVID-19 pandemic, the actual drop-out for the CMR visit after 4 months was higher than anticipated, but this did not result in the recommendation of the DSMB or ethical committee to extend enrollment.…”

Reperfusion Strategies in Acute Myocardial Infarction: State of the Art

“…61 Intravenous or ic administration of melatonin was not associated with a reduction in the size of AMI and increased left ventricular remodeling; 62 however, when administration was early, it reduced the size of the infarction. 63 The ic injection of morphine did not reduce the size of the AMI in patients undergoing PCI PCI 64 . There was no reduction in the size of AMI in patients treated with a mineralocorticoid receptor antagonist before reperfusion, but there was an improvement in left ventricular remodeling.…”