Timing of Metoprolol Administration and Cardioprotective Effect in STEMI
How does the timing of administration of intravenous (IV) metoprolol impact its cardioprotective effect in the reduction of infarct size in ST-segment elevation myocardial infarction (STEMI)?
This was a post hoc analysis of the METOCARD-CNIC (effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion) trial. In the METOCARD-CNIC trial, patients were recruited and randomized to 15 mg IV metoprolol or control before arterial access, either during ambulance transit or at the hospital performing primary percutaneous coronary intervention (i.e., there was significant heterogeneity in terms of timing of metoprolol administration). The primary endpoint was myocardial infarct size, assessed by cardiac magnetic resonance (CMR) at 5-7 days post-infarction. To study the impact of metoprolol timing on cardioprotection, the authors divided patients allocated to IV metoprolol into two groups according to whether the metoprolol-to-reperfusion interval was longer than the median value (long-interval group) or shorter (short-interval group). The authors also performed a controlled validation study in 51 pigs subjected to 45 minutes of ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (-25 minutes) or short (-5 minutes) pre-perfusion interval, IV metoprolol post-reperfusion (+60 minutes), or IV vehicle.
A total of 218 patients were included in this analysis. The median time from 15 mg metoprolol bolus-to-reperfusion was 53 minutes. Compared with patients in the short-interval group, those with longer 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. In the animal study, the long-interval group (IV metoprolol 25 minutes before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR).
Among patients without contraindications to beta-blockade, the sooner metoprolol is injected in the course of STEMI, the smaller the infarct and the higher the LVEF.
This is a valuable study that lends support to American and European guidelines for the use of IV beta-blockade for STEMI patients who are without contraindications and are hypertensive or show ‘signs of ongoing ischemia.’ Furthermore, the authors provide support for early IV administration of beta-blockade in those without contraindications (exclusion criteria for METOCARD-CNIC were signs of heart failure, systolic blood pressure <120 mm Hg, or any degree of atrioventricular block). Although the study was a post hoc analysis, the authors tested the hypothesis generated in an experimental model of STEMI (pig ischemia/reperfusion).
Keywords: Acute Coronary Syndrome, Adrenergic beta-Antagonists, Infarction, Magnetic Resonance Spectroscopy, Myocardial Infarction, Myocardial Ischemia, Metoprolol, Percutaneous Coronary Intervention, Reperfusion, Stroke Volume, Ventricular Function
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