Impact of the timing of metoprolol administration during STEMI on infarct size and ventricular function

Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-t...

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Authors: García Ruiz, José María, Fernández Jiménez, Rodrigo, García Álvarez, Ana, Pizarro, Gonzalo, Galán Arriola, Carlos, Fernández Friera, Leticia, Mateos, Alonso, Nuño Ayala, Mario, Agüero, Jaume, Sánchez González, Javier, García Prieto, Jaime, López Melgar, Beatriz, Martínez Tenorio, Pedro, López Martín, Gonzalo J., Macías, Ángel, Pérez Asenjo, Braulio, Cabrera Rodríguez, José Ángel
Format: article
Publication Date:2016
Country:España
Institution:Universidad Europea (UEM)
Repository:ABACUS. Repositorio de Producción Científica
Language:English
OAI Identifier:oai:abacus.universidadeuropea.com:11268/6024
Online Access:http://hdl.handle.net/11268/6024
Access Level:Open access
Keyword:Resonancia magnética nuclear (Medicina)
Infarto de miocardio
Enfermedad cardiovascular
Sistema cardiovascular
Description
Summary:Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval. We performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short- and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (−25 min) or short (−5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings. For 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR). In anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study.