C Michael Gibson1, Robert P Giugliano2, Robert A Kloner3, Christoph Bode4, Michal Tendera5, András Jánosi6, Bela Merkely7, Jacek Godlewski8, Rim Halaby9, Serge Korjian9, Yazan Daaboul9, Anjan K Chakrabarti10, Kathryn Spielman11, Brandon J Neal11, W Douglas Weaver12. 1. PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW-459, Boston, MA 02215, USA mgibson@bidmc.harvard.edu. 2. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 3. Huntington Medical Research Institutes, Pasadena, CA, USA Cardiovascular Division, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 4. Cardiology and Angiology I, Heart Center, Freiburg University, Freiberg, Germany. 5. 3rd Department of Cardiology, School of Medicine in Katowice, Medical University of Medicine, Katowice, Poland. 6. Gottsegen Gyorgy National Institute of Cardiology, Budapest, Hungary. 7. Semmelweis University Heart Center, Budapest, Hungary. 8. Krakowski Szpital Specjalistyczny im. Jana Pawla II, Krakow, Poland. 9. Harvard Medical School, Boston, MA, USA. 10. Eastern Virginia Medical School, Norfolk, VA, USA. 11. PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW-459, Boston, MA 02215, USA. 12. Henry Ford Hospital, Detroit, MI, USA.
Abstract
AIMS: Among patients with ST-elevation myocardial infarction (STEMI), reperfusion injury contributes to additional myocardial damage. MTP-131 is a cell-permeable peptide that preserves the integrity of cardiolipin, enhances mitochondrial energetics, and improves myocyte survival during reperfusion. METHODS AND RESULTS: EMBRACE STEMI is a multicentre, randomized, double-blind Phase 2a trial that evaluated the efficacy and safety of MTP-131 vs. placebo infused at a rate of 0.05 mg/kg/h for 1 h among first-time anterior STEMI subjects undergoing primary percutaneous coronary intervention (PCI) for a proximal or mid left anterior descending (LAD) artery occlusion. Administration of MTP-131 was not associated with a significant reduction in the primary endpoint, infarct size by creatine kinase-myocardial band (CK-MB) area under the curve (AUC) over 72 h (5785 ± 426 ng h/mL in placebo vs. 5570 ± 486 ng h/mL in MTP-131; ITALIC! P = NS). MTP-131 was not associated with an improvement in pre-specified magnetic resonance imaging, angiographic, electrocardiographic, or clinical outcomes. CONCLUSION: Among subjects with first-time anterior STEMI due to a proximal or mid LAD lesion who undergo successful PCI, administration ofMTP-131 was safe and well tolerated. Treatment with MTP-131 was not associated with a decrease in myocardial infarct size as assessed by AUC0-72 of CK-MB. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: Among patients with ST-elevation myocardial infarction (STEMI), reperfusion injury contributes to additional myocardial damage. MTP-131 is a cell-permeable peptide that preserves the integrity of cardiolipin, enhances mitochondrial energetics, and improves myocyte survival during reperfusion. METHODS AND RESULTS: EMBRACE STEMI is a multicentre, randomized, double-blind Phase 2a trial that evaluated the efficacy and safety of MTP-131 vs. placebo infused at a rate of 0.05 mg/kg/h for 1 h among first-time anterior STEMI subjects undergoing primary percutaneous coronary intervention (PCI) for a proximal or mid left anterior descending (LAD) artery occlusion. Administration of MTP-131 was not associated with a significant reduction in the primary endpoint, infarct size by creatine kinase-myocardial band (CK-MB) area under the curve (AUC) over 72 h (5785 ± 426 ng h/mL in placebo vs. 5570 ± 486 ng h/mL in MTP-131; ITALIC! P = NS). MTP-131 was not associated with an improvement in pre-specified magnetic resonance imaging, angiographic, electrocardiographic, or clinical outcomes. CONCLUSION: Among subjects with first-time anterior STEMI due to a proximal or mid LAD lesion who undergo successful PCI, administration of MTP-131 was safe and well tolerated. Treatment with MTP-131 was not associated with a decrease in myocardial infarct size as assessed by AUC0-72 of CK-MB. Published on behalf of the European Society of Cardiology. All rights reserved.
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