1. 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.

2. There are no potential conflicts of interest. Conflicts of interest

3. Background STEMI treated by pPCI results in low acute mortality. However, STEMI survivors are at high risk of repetitive events (heart failure, death,..)  huge socioeconomic burden. Therapies able to reduce infarct size are extensively sought: “smaller infarctions  better long term heart performance (LVEF)  fewer adverse clinical events. Infarct size is a main determinant of long term morbi- mortality (others LVEF, LVESV, MVO).

4. Background  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 pCI era. The effect of early i.v. ß-blocker on infarct size (and long term LV function is unclear.

5. 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.

6. Clinical Implications

7. 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 SUMMA112, Madrid 061 Galicia, AAMUR, Madrid

8. Metoprolol i.v pre-reperfusion Control (no metoprolol pre-reperfusion) 1 st STEMI revascularized <6hr (N=270) Anterior wall AMI, Killip I-II Metoprolol Oral / 12 hr (first Dose 12-24hr post-reperfusion) Primary PCI Primary endpoint: Infarct Size by MRI (d7 post-MI, N=220). already reported (Circulation 2013;128:1495-1503). Cardiovascular events (> 12 months). Main pre-specified secondary endpoint: LV function on MRI 6 months after STEMI (N=202). METOCARD-CNIC study design

9. 20% reduction. Day 7 results

11. Improved Perfusion García-Lunar, Pizarro et al ACC 2014 (ORAL Presentation). i.v. metoprolol pre-reperfusion reduces Microvascular Obstruction (even after adjusting for infarct size). N=220.

12. 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.

13. Results i.v. metoprolol pre-reperfusion improves long term (6 months) LVEF. N=101 49±10% 45±12% N=101

14. Reduction of chronic post-infarction LV systolic dysfunction. Results N=101

15. Results Reduction of Implantable Cardioverter-Defibrillator indications. N=101

16. Results Benefits attributable to acute effect of early i.v. metoprolol.

17. Results MRI data on 6 months MRI

18. Results

19. Follow-up (confidential)

20. Conclusions In Killip-I-II anterior STEMI patients reperfused by pPCI 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).