Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Myocardial and Microvascular Injury in Acute Myocardial Infarction: Insights From the Randomized MonAMI Trial

Abstract

Background Intravenous morphine administration can adversely affect platelet inhibition induced by P2Y12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury. Methods and Results Patients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P=0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P=0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P=0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14–0.93 [P=0.035]). There was no significant difference in infarct size (P=0.491) and extent (P=0.753) or presence (P=0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group. Conclusions In this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02627950.