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

Philippe Le Corvoisier, Romain Gallet, Pierre-François Lesault, Etienne Audureau, Muriel Paul, Julien Ternacle, Saïd Ghostine, Stéphane Champagne, Raphaele Arrouasse, Dalila Bitari, Gauthier Mouillet, Jean-Luc Dubois-Randé, Alain Berdeaux, Bijan Ghaleh, Jean-François Deux, Emmanuel Teiger, Philippe Le Corvoisier, Romain Gallet, Pierre-François Lesault, Etienne Audureau, Muriel Paul, Julien Ternacle, Saïd Ghostine, Stéphane Champagne, Raphaele Arrouasse, Dalila Bitari, Gauthier Mouillet, Jean-Luc Dubois-Randé, Alain Berdeaux, Bijan Ghaleh, Jean-François Deux, Emmanuel Teiger

Abstract

Background: Experimental 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.

Methods: Ninety-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.

Results: Infarct 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.

Conclusions: Intracoronary 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 registration: ClinicalTrials.gov, NCT01186445 (date of registration: August 23, 2010).

Keywords: Cardioprotection; Infarct size; Morphine; Reperfusion injury; STEMI.

Conflict of interest statement

Ethics approval and consent to participate

The study was performed in accordance with the ethical principles stated in the Declaration of Helsinki and good clinical practice principles. The protocol was approved by an ethics committee (institutional review board of the Pitie-Salpetriere hospital, Paris, France) and all patients gave written informed consent.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Patient flowchart
Fig. 2
Fig. 2
Areas under the curves and peak of serum troponin T (TnT) (Panel a and c) and creatine kinase CK (panel b and d) levels. No difference was observed between groups. Results are shown as boxplots, with each box representing the interquartile range (1st to 3rd quartile, IQR), the line within the box indicating the median, and the whiskers extending to 1.5 times the IQR above and below the box

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