Background-The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). Methods and Results-Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean±SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6±15.3 versus 32.0±22.2 g; adjusted difference, −6.52; 95% confidence interval, −11.39 to −1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was −8.13 (95% confidence interval, −13.10 to −3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). Conclusions-In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI.

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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).

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CorrespondenceWe appreciate the interest of and comments by Drs Argulian and Messerli on our recently published study.1 Defining inclusion and exclusion criteria, along with dose selection of the administered pharmacological therapy, is critical in the early stages of a clinical trial design. The scientific method strongly recommends performing a profound bibliographic research in this regard, and for this purpose, we carefully reviewed previously conducted trials on the use of β-blockers in the setting of ST-segment-elevation acute myocardial infarction, taking note of the strengths and weaknesses of each of them.Thus, for the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial, we randomized anterior myocardial infarctions revascularized by primary angioplasty in <6 hours from symptom onset because this is the population that most benefits from any cardioprotective intervention. More important, and for safety reasons, we designed a trial to recruit patients with no obvious contraindications for the administration of intravenous metoprolol. Because β-blockers are clearly contraindicated in the acute phase of severe heart failure, patients in Killip-Kimball classes III and IV were strictly excluded from randomization, 2 fulfilling the primum non nocere principle. Patients randomized to intravenous metoprolol received up to three 5-mg boluses of metoprolol tartrate 2 minutes apart, following the same scheme as that in the Thrombolysis in Myocardial Infarction (TIMI) II-B trial, 3 closely checking for the presence of contraindications-heart rhythm and rate, PR-interval duration, blood pressure, and clinical examination-before the administration of every single bolus. Similarly, the dose and timing for oral metoprolol after reperfusion were selected according to current recommendations. 4 Thus, an initial low dose of 25 mg metoprolol twice a day was initiated in the vast majority of the patients included in the trial within the first 24 hours of admission and was carefully titrated according to clinical judgment.The increase in mortality observed in patients with initial systolic blood pressure <120 mm Hg or Killip-Kimball class III in the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) trial 5 is one of the main reasons why clinical practice guidelines do not emphasize early intravenous β-blocker initiation in ST-segmentelevation myocardial infarction. These patients were systematically excluded from our trial; consequently, prereperfusion administration of intravenous metoprolol did not increase the incidence of major adverse cardiac events in our study. This reinforces the contraindications for intravenous β-blocker therapy in patients with overt heart failure but supports its use in the population that can potentially benefit most from this inexpensive, safe, and effective intervention.Although there are other important differences between the METOCARD-CNIC trial and previously conducted studies evaluating the effect of β-blockers in the settin...

Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.

Introduction and Objectives: Current clinical guidelines for ST-segment elevation myocardial infarction (STEMI) suggest prehospital activation of the cardiac catheterization team. In previous protocols in our center activation occurred once patients arrived at the hospital. In January 2011, we initiated a new primary angioplasty activation protocol from prehospital locations. Our objective was to quantify the influence of this change on reperfusion times. Methods: A total of 173 consecutive STEMI patients (n=73/100 before/after initiation of the new protocol), diagnosed in a prehospital setting within 12 hours of symptom onset, were analyzed. The time between the patient's arrival at the hospital and beginning of the angioplasty procedure was termed the cath lab activation delay. Results: The new protocol resulted in a 37-min reduction in system delay (166 [132---235] min before vs. 129 [105---166] min after, p<0.001), mostly driven by a 64% reduction in cath lab activation delay (55 [0---79] min before vs. 20 [0---54] min after, p=0.001). This reduction was mainly observed outside working hours. The percentage of patients treated with a system delay ≤120 min increased from 14.5% before the new protocol to 41.8% afterwards (p=0.001). Conclusions: Prehospital activation of the cardiac catheterization team resulted in earlier reperfusion of STEMI patients. Angioplastia coronária; Enfarte do miocárdio; Tempo de isquemia; Atraso no tratamento Ativação pré-hospitalar da equipa de angioplastia primária no enfarte agudo miocárdio com elevação do segmento ST Resumo Introdução e objetivos: As atuais diretrizes clínicas aquando da ocorrência de um enfarte agudo miocárdio com elevação do segmento ST (STEMI) sugerem a ativação da equipa de angioplastia primária ao nível pré-hospitalar. Protocolos anteriores contemplam a ativação da referida equipa assim que os pacientes chegam ao hospital. Em janeiro de 2011, o nosso centro iniciou um novo protocolo de ativação da equipa de angioplastia primária em localização pré-hospitalar de modo a quantificar a influência de tal alteração nos tempos de reperfusão. Métodos: Foram analisados 173 pacientes consecutivos com STEMI, cujo diagnóstico se efetuou em local pré-hospitalar em 12 horas desde o início dos sintomas (n = 73/100 antes/ após início do novo protocolo). O tempo que decorreu entre a chegada do paciente ao hospital e o inicio do procedimento de angioplastia foi designado Cath Lab Activation Delay. Resultados: O novo protocolo refletiu uma redução de 37 minutos no System Delay (166 [132 ---235] antes versus 129 [105 ---166] minutos depois, p<0.001), que se deveu primordialmente à redução de 64% no Cath Lab Activation Delay (55 [0 ---79] minutos antes versus 20 [0 ---54] minutos depois, p = 0,001). Tal redução observou-se principalmente em horário pós-laboral. A percentagem de pacientes tratados com um System Delay ≤ 120 minutos aumentou de 14,5%, antes do início do novo protocolo, para 41,8% após (p = 0,001). Conclusões: A ativação da equipa de angioplastia primária ao nível...

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