Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function.
Author: Mateos Rodríguez, Alonso
Abstract: BACKGROUND Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment
elevation myocardial infarction (STEMI).
OBJECTIVES 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.
METHODS 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 (þ60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed
in the acute and chronic phases in both clinical and experimental settings.
RESULTS 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 ¼ 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; p ¼ 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).
CONCLUSIONS 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.
Universal identifier: http://hdl.handle.net/10641/1176
Date: 2016
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