Expert Review: Ischemic Heart Disease

Long term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial.

Background and knowledge gap
β-blockers reduce mortality when administered after an AMI, and are a class IA indication in this context. Experimental models have shown that intravenous administration of metoprolol before (but not after) reperfusion of STEMI reduces infarct size1,2. However, whether early β-blocker administration is able to reduce infarct size in humans is still a subject of debate.

Aim of the Study
The study aimed:
a) To assess the long term effect (six moths) of iv metoprolol administration on left ventricular ejection fraction (LVEF), primarily assessed by MRI
b) To evaluate long term clinical benefits (mean follow up, 2 years)
-composite of death, readmission due to heart failure, re-infarction and malignant ventricular arrhythmias.
-rate of implantable cardioverter-defibrillator (ICD) indication

Methods
Elegible patients were individuals (18-80 years) with clinical presentation of STEMI (≥30 minutes of duration), defined as ST-segment elevation ≥2 mm in ≥2 contiguous leads V1-V5, and an estimated time from symptom onset to reperfusion ≤ 6 hours. Patients in Killip class III or IV were excluded.
The study randomized 270 patients to iv metoprolol (n=131) or no treatment (control, n=139) before reperfusion. Patients in the metorprolol group received up to 3 iv bolus of 5mg of metoprolol, with an interval of 2 minutes between bolus. In addition, all patients without contraindication received oral metoprolol within the first 24 hours.

Results
According to the objetctives of the study:
a) Mean LVEF assessed by MRI at 6 months MRI was higher after iv metoprolol (48.7±9.9% vs. 45.0±11.7% in controls; adjusted treatment effect 3.49%; 95% confidence interval [CI], 0.44 to 6.55%; p=0.025). A significantly lesser proportion of patients in the iv metoprolol group developed The severely depressed LVEF (≤35%) at 6 months (11% vs. 27%, p=0.006).
b) The pre-specified composite of death, heart failure admission, re-infarction, and malignant arrhythmia at a median follow-up of 2 years, occurred in 10.8% in iv metoprolol vs. 18.3% in controls, adjusted HR: 0.55; 95% CI, 0.26 to 1.04; p=0.065. Heart failure admission was significantly lower in iv. metoprolol (HR: 0.32; 95% CI, 0.015 to 0.95; P=0.046).
Fewer participants in the metoprolol group had an indication for a defibrillator (7% vs. 20%, p=0.012).

Clinical Impact:
The METOCARD-CNIC shows how the early administration of iv metoprolol in patients with anterior STEMI and no heart failure symptoms (killip I-II) undergoing primary angioplasty results in improved left ventricular ejection fraction at 6 months. In addition, a reduced incidence of severe LV systolic dysfunction and ICD indications is seen. Patients receiving this treatment strategy are less likely to develop heart failure that needs hospital admission.

This is the first study reporting the infarct limiting effect of beta-blockers beyond revascularization by primary angioplasty, and the derived benefits of this goal in terms of LVEF, ICD indications and heart failure admissions. Given that iv beta blockade is permitted by clinical guidelines (class IIA indication), this strategy might be implemented universally immediately for patients with no contraindications (mainly overt heart failure: killip-class III-IV).

Corresponding author from original paper
Dr. Borja Ibáñez
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
Electronic address: bibanez@cnic.es

References
1.- Ibanez B, Prat-González S, Speidl WS, Vilahur G, Pinero A, Cimmino G, et al. Early metoprolol administration before coronary reperfusion results in increased myocardial salvage: analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation. 2007 Jun 12;115(23):2909-16

2.- Ibanez B, Fuster V, Jiménez-Borreguero J, Badimon JJ. Lethal myocardial reperfusion injury: a necessary evil? Int J Cardiol. 2011 Aug 18;151(1):3-11.

Citation: Pizarro G, Fernández-Friera L, Fuster V, Fernández-Jiménez R, García-Ruiz JM, García-Álvarez A, Mateos A, Barreiro MV, Escalera N, Rodriguez MD, de Miguel A, García-Lunar I, Parra-Fuertes JJ, Sánchez-González J, Pardillos L, Nieto B, Jiménez A, Abejón R, Bastante T, de Vega VM, Cabrera JA, López-Melgar B, Guzman G, García Prieto J, Mirelis JG, Zamorano JL, Albarrán A, Goicolea J, Escaned J, Pocock S, Iñiguez A, Fernández-Ortiz A, Sánchez-Brunete V, Macaya C, Ibanez B. Long term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial, Journal of the American College of Cardiology (2014), doi: 10.1016/j.jacc.2014.03.014

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