Long Term Benefit Of Early Prereperfusion Metoprolol Administration
Long Term Benefit Of Early Pre-reperfusion Metoprolol Administration In Patients With Acute Myocardial Infarction: Results From The METOCARD-CNIC trial. Borja Ibanez, G Pizarro, L Fernandez-Friera, R Fernandez-Jiménez, JM García-Ruiz, A García-Álvarez, A Mateos, A Iñiguez, I Garcia-Lunar, S Pocock, A Fernandez-Órtiz, V Sánchez-Brunete, C Macaya, Valentin Fuster. On behalf of the METOCARD-CNIC researchers.
Conflicts of interest There are no potential conflicts of interest.
Background STEMI treated by p. PCI results in low acute mortality. However, STEMI survivors are at high risk of repetitive events (heart failure, death, . . ) huge socioeconomic burden. Infarct size is a main determinant of long term morbimortality (others LVEF, LVESV, MVO). Therapies able to reduce infarct size are extensively sought: “smaller infarctions better long term heart performance (LVEF) fewer adverse clinical events.
Background The effect of early i. v. ß-blocker on infarct size (and long term LV function is unclear. Several trials in the pre-reperfusion era (inconclusive results). Roberts et al, Hjalmarson et al, Yusuf et al, MILIS, . . ONE single randomized trial in the thrombolytic era. van de Werf et al J Am Coll Cardiol 1993. NO trials in the p. CI era.
Background Pre-Clinical data: Metoprolol during ongoing ischemia reduces infarct size in the pig model of STEMI. Ibanez B, Fuster V, Sanz J, Badimon J et al. Circulation 2007. Pre- but not post-reperfusion i. v. metoprolol reduces infarct size in the pig model of STEMI. Ibanez B, Fuster V, Sanz J, Badimon J et al. Int J Cardiol 2011.
Clinical Implications ACC/AHA guidelines 2013
METOCARD-CNIC H. Clínico San Carlos, Madrid H. Doce de Octubre, Madrid H. Puerta de Hierro, Madrid H. La Princesa, Madrid H. Meixoeiro, Vigo H. León H. M de Valdecilla, santander SUMMA 112, Madrid 061 Galicia, AAMUR, Madrid
METOCARD-CNIC study design 1 st STEMI revascularized <6 hr (N=270) Anterior wall AMI, Killip I-II Metoprolol i. v pre -reperfusion Control (no metoprolol pre-reperfusion) Primary PCI Metoprolol Oral / 12 hr (first Dose 12 -24 hr post-reperfusion) Primary endpoint: Infarct Size by MRI (d 7 post-MI, N=220). already reported (Circulation 2013; 128: 1495 -1503). Main pre-specified secondary endpoint: LV function on MRI 6 months after STEMI (N=202). Cardiovascular events (> 12 months).
Day 7 results 20% reduction.
Day 7 results
Improved Perfusion i. v. metoprolol pre-reperfusion reduces Microvascular Obstruction (even after adjusting for infarct size). N=220. García-Lunar, Pizarro et al ACC 2014 (ORAL Presentation).
Today we present the pre-specified evaluation on long-term (6 months) LVEF (primary MRI measurement) and the effect on clinical endpoints of the METOCARD-CNIC trial.
Results i. v. metoprolol pre-reperfusion improves long term (6 months) LVEF. 49± 10% 45± 12% N=101
Results Reduction of chronic post-infarction LV systolic dysfunction. N=101
Results Reduction of Implantable Cardioverter-Defibrillator indications. N=101
Results Benefits attributable to acute effect of early i. v. metoprolol.
Results MRI data on 6 months MRI
Results
Follow-up (confidential)
Conclusions In Killip-I-II anterior STEMI patients reperfused by p. PCI within 6 hours from symptoms onset, the early pre-reperfusion i. v. metoprolol administration results in: Reduced infarct size & slightly increased LVEF at one week. Increased long term LVEF (6 months MRI). Reduced cases of severely depressed. Trend for reduced long-term hard endpoints (driven by reduction of heart failure readmission). . These results set the basis for a large RCT powered to detect differences in clinical endpoints (MOVE ON! trial).
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