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J Am Coll Cardiol. 2016 May 10;67(18):2093-2104. doi: 10.1016/j.jacc.2016.02.050. Epub 2016 Apr 3.

Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function.

Author information

1
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Central de Asturias, Oviedo, Spain.
2
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
3
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clinic, Barcelona, Spain.
4
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Quirón, Universidad Europea de Madrid, & Clínica Ruber-Quirónsalud, Madrid, Spain.
5
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
6
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario HM Montepríncipe-CIEC, Madrid, Spain.
7
Servicio de Urgencia Médica de Madrid-SUMMA112, Madrid, Spain; Universidad Francisco de Vitoria, Madrid, Spain.
8
Philips Healthcare Iberia, Iberia, Spain.
9
Servicio de Urgencia Médica de Madrid-SUMMA112, Madrid, Spain.
10
Hospital Universitario Quirón, Universidad Europea de Madrid, & Clínica Ruber-Quirónsalud, Madrid, Spain.
11
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
12
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Instituto de Investigación Sanitaria & Department of Cardiology, Fundación Jiménez Díaz Hospital, Madrid, Spain. Electronic address: bibanez@cnic.es.

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 (+60 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 = 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).

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.

KEYWORDS:

cardiac magnetic resonance; cardioprotection; left ventricular ejection fraction; myocardial infarction; reperfusion injury

PMID:
27052688
DOI:
10.1016/j.jacc.2016.02.050
[Indexed for MEDLINE]
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