Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).
OBJECTIVE
The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events.


BACKGROUND
Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI).


METHODS
The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up.


RESULTS
Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046).


CONCLUSIONS
In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700).
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Quirón-Universidad Europea de Madrid, Madrid, Spain.
Gonzalo
G
Pizarro
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Montepríncipe, Madrid, Spain.
Leticia
L
Fernández-Friera
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York.
Valentin
V
Fuster
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
Rodrigo
R
Fernández-Jiménez
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Central de Asturias, Oviedo, Spain.
José M
JM
García-Ruiz
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clinic, Barcelona, Spain.
Ana
A
García-Álvarez
Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain.
Alonso
A
Mateos
Servicio de Emergencia Medica 061 de Galicia, Galicia, Spain.
María V
MV
Barreiro
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Noemí
N
Escalera
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Maite D
MD
Rodriguez
Complejo Hospitalario Universitario de Vigo-Meixoeiro, Pontevedra, Spain.
Antonio
A
de Miguel
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Quirón-Universidad Europea de Madrid, Madrid, Spain; Hospital Universitario Puerta de Hierro, Madrid, Spain.
Inés
I
García-Lunar
Hospital Universitario Doce de Octubre, Madrid, Spain.
Juan J
JJ
Parra-Fuertes
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Philips Healthcare, Madrid, Spain.
Javier
J
Sánchez-González
Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain.
Luis
L
Pardillos
Complejo Hospitalario Universitario de Vigo-Meixoeiro, Pontevedra, Spain.
Beatriz
B
Nieto
Hospital Universitario León, León, Spain.
Adriana
A
Jiménez
Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain.
Raquel
R
Abejón
Hospital de la Princesa, Madrid, Spain.
Teresa
T
Bastante
Hospital Universitario Quirón-Universidad Europea de Madrid, Madrid, Spain.
Vicente
V
Martínez de Vega
Hospital Universitario Quirón-Universidad Europea de Madrid, Madrid, Spain.
José A
JA
Cabrera
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Doce de Octubre, Madrid, Spain.
Beatriz
B
López-Melgar
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario La Paz, Madrid, Spain.
Gabriela
G
Guzman
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Jaime
J
García-Prieto
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Puerta de Hierro, Madrid, Spain.
Jesús G
JG
Mirelis
Hospital Clínico San Carlos, Madrid, Spain.
José Luis
JL
Zamorano
Hospital Universitario Doce de Octubre, Madrid, Spain.
Agustín
A
Albarrán
Hospital Universitario Puerta de Hierro, Madrid, Spain.
Javier
J
Goicolea
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
Javier
J
Escaned
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; London School of Hygiene & Tropical Medicine, London, United Kingdom.
Stuart
S
Pocock
Complejo Hospitalario Universitario de Vigo-Meixoeiro, Pontevedra, Spain.
Andrés
A
Iñiguez
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
Antonio
A
Fernández-Ortiz
Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain.
Vicente
V
Sánchez-Brunete
Hospital Clínico San Carlos, Madrid, Spain.
Carlos
C
Macaya
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain. Electronic address: bibanez@cnic.es.
Borja
B
Ibanez
D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D061345:Early Medical Intervention; D006801:Humans; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D016037:Single-Blind Method; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D058671:Adrenergic beta-1 Receptor Antagonists; D008790:Metoprolol
ICD; LVEF; PCI; STEMI; beta-adrenergic receptors; heart failure; infarct size; magnetic resonance imaging; metoprolol; myocardial infarction