Response to Letter Regarding Article, “Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial”
2014; Lippincott Williams & Wilkins; Volume: 130; Issue: 3 Linguagem: Inglês
10.1161/circulationaha.114.009352
ISSN1524-4539
AutoresBorja Ibáñez, Carlos Macaya, Vicente Sánchez-Brunete, Gonzalo Pizarro, Leticia Fernández‐Friera, Alonso Mateos, Antonio Fernández-Ortı́z, José M. García‐Ruiz, Ana García‐Álvarez, Andrés Íñiguez, Luis Jesús Jiménez‐Borreguero, Pedro López‐Romero, Rodrigo Fernández‐Jiménez, Javier Goicolea, Borja Ruiz-Mateos, Teresa Bastante, Mercedes Arias, José Antonio Iglesias Vázquez, Maite Rodriguez, Noemí Escalera, Carlos Acebal, José Ángel Cabrera, Juan Valenciano, Armando Pérez de Prado, María J. Fernández-Campos, Isabel Casado, Juan C. Garcı́a-Rubira, Jaime García‐Prieto, David Sanz‐Rosa, Carlos Cuellas, Rosana Hernández‐Antolín, Agustín Albarrán, Felipe Fernández‐Vázquez, José M. de la Torre-Hernández, Stuart J. Pocock, Ginés Sanz, Valentı́n Fuster,
Tópico(s)Heart Failure Treatment and Management
ResumoHomeCirculationVol. 130, No. 3Response to Letter Regarding Article, "Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter Regarding Article, "Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial" Borja Ibanez, MD Carlos Macaya, MD Vicente Sánchez-Brunete, MD Gonzalo Pizarro, MD, Leticia Fernández-Friera, MD, Alonso Mateos, MD, Antonio Fernández-Ortiz, MD, José M. García-Ruiz, MD and Ana García-Álvarez, MD Andrés Iñiguez, MD Jesús Jiménez-Borreguero, MD, Pedro López-Romero, PhD and Rodrigo Fernández-Jiménez, MD Javier Goicolea, MD Borja Ruiz-Mateos, MD Teresa Bastante, MD Mercedes Arias, MD José A. Iglesias-Vázquez, MD Maite D. Rodriguez, RN and Noemí Escalera, BPT Carlos Acebal, MD José A. Cabrera, MD Juan Valenciano, MD Armando Pérez de Prado, MD María J. Fernández-Campos, MD Isabel Casado, MD Juan C. García-Rubira, MD Jaime García-Prieto, BSc and David Sanz-Rosa, PhD Carlos Cuellas, MD Rosana Hernández-Antolín, MD Agustín Albarrán, MD Felipe Fernández-Vázquez, MD José M. de la Torre-Hernández, MD Stuart Pocock, PhD and Ginés Sanz, MD Valentin Fuster, MD Borja IbanezBorja Ibanez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain Carlos MacayaCarlos Macaya Hospital Clínico San Carlos, Madrid, Spain Vicente Sánchez-BruneteVicente Sánchez-Brunete Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain Gonzalo PizarroGonzalo Pizarro Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain , Leticia Fernández-FrieraLeticia Fernández-Friera Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain , Alonso MateosAlonso Mateos Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain , Antonio Fernández-OrtizAntonio Fernández-Ortiz Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain , José M. García-RuizJosé M. García-Ruiz Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain and Ana García-ÁlvarezAna García-Álvarez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain Andrés IñiguezAndrés Iñiguez Complejo Hospitalario Universitario de Vigo-Meixoeiro, Pontevedra, Spain Jesús Jiménez-BorregueroJesús Jiménez-Borreguero Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain , Pedro López-RomeroPedro López-Romero Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain and Rodrigo Fernández-JiménezRodrigo Fernández-Jiménez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain Javier GoicoleaJavier Goicolea Hospital Universitario Puerta de Hierro, Madrid, Spain Borja Ruiz-MateosBorja Ruiz-Mateos Hospital Clínico San Carlos, Madrid, Spain Teresa BastanteTeresa Bastante Hospital Universitario de la Princesa, Madrid, Spain Mercedes AriasMercedes Arias Complejo Hospitalario Universitario de Vigo-Meixoeiro, Pontevedra, Spain José A. Iglesias-VázquezJosé A. Iglesias-Vázquez Servicio de Emergencia Medica 061 de Galicia-Sur, Galicia, Spain Maite D. RodriguezMaite D. Rodriguez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain and Noemí EscaleraNoemí Escalera Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain Carlos AcebalCarlos Acebal Hospital Clínico San Carlos, Madrid, Spain José A. CabreraJosé A. Cabrera Hospital Universitario Quirón, Madrid, Spain Juan ValencianoJuan Valenciano Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain Armando Pérez de PradoArmando Pérez de Prado Hospital Universitario León, León, Spain María J. Fernández-CamposMaría J. Fernández-Campos Servicio de Urgencia Médica de Madrid (SUMMA 112), Madrid, Spain Isabel CasadoIsabel Casado Servicio de Atención Médica Urgente (SAMUR)–Protección Civil, Madrid, Spain Juan C. García-RubiraJuan C. García-Rubira Hospital Clínico San Carlos, Madrid, Spain Jaime García-PrietoJaime García-Prieto Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain and David Sanz-RosaDavid Sanz-Rosa Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain Carlos CuellasCarlos Cuellas Hospital Universitario León, León, Spain Rosana Hernández-AntolínRosana Hernández-Antolín Hospital Clínico San Carlos, Madrid, Spain Agustín AlbarránAgustín Albarrán Hospital Universitario Doce de Octubre, Madrid, Spain Felipe Fernández-VázquezFelipe Fernández-Vázquez Hospital Universitario León, León, Spain José M. de la Torre-HernándezJosé M. de la Torre-Hernández Hospital Universitario Marqués de Valdecilla, Santander, Spain Stuart PocockStuart Pocock Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain and Ginés SanzGinés Sanz Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain Valentin FusterValentin Fuster The Zena and Michael A. Wiener CVI, Mount Sinai School of Medicine, New York, NY Originally published15 Jul 2014https://doi.org/10.1161/CIRCULATIONAHA.114.009352Circulation. 2014;130:e19–e20We 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) trial5 is one of the main reasons why clinical practice guidelines do not emphasize early intravenous β-blocker initiation in ST-segment–elevation 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 setting of ST-segment–elevation acute myocardial infarction, we totally agree with Drs Argulian and Messerli that a careful design of the dose and timing of any given intervention can make a huge difference in the outcomes of a trial.Borja Ibanez, MDCentro Nacional de Investigaciones CardiovascularesCarlos III (CNIC)Madrid, SpainCarlos Macaya, MDHospital Clínico San CarlosMadrid, SpainVicente Sánchez-Brunete, MDServicio de Urgencia Médica de Madrid (SUMMA 112)Madrid, SpainGonzalo Pizarro, MDLeticia Fernández-Friera, MDAlonso Mateos, MDAntonio Fernández-Ortiz, MDJosé M. García-Ruiz, MDAna García-Álvarez, MDCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)Madrid, SpainAndrés Iñiguez, MDComplejo Hospitalario Universitario de Vigo-MeixoeiroPontevedra, SpainJesús Jiménez-Borreguero, MDPedro López-Romero, PhDRodrigo Fernández-Jiménez, MDCentro Nacional de Investigaciones CardiovascularesCarlos III (CNIC)Madrid, SpainJavier Goicolea, MDHospital Universitario Puerta de HierroMadrid, SpainBorja Ruiz-Mateos, MDHospital Clínico San CarlosMadrid, SpainTeresa Bastante, MDHospital Universitario de la PrincesaMadrid, SpainMercedes Arias, MDComplejo Hospitalario Universitario de Vigo-MeixoeiroPontevedra, SpainJosé A. Iglesias-Vázquez, MDServicio de Emergencia Medica 061 de Galicia-SurGalicia, SpainMaite D. Rodriguez, RNNoemí Escalera, BPTCentro Nacional de InvestigacionesCardiovasculares Carlos III (CNIC)Madrid, SpainCarlos Acebal, MDHospital Clínico San CarlosMadrid, SpainJosé A. Cabrera, MDHospital Universitario QuirónMadrid, SpainJuan Valenciano, MDServicio de Urgencia Médica de Madrid (SUMMA 112)Madrid, SpainArmando Pérez de Prado, MDHospital Universitario LeónLeón, SpainMaría J. Fernández-Campos, MDServicio de Urgencia Médica de Madrid (SUMMA 112)Madrid, SpainIsabel Casado, MDServicio de Atención Médica Urgente (SAMUR)–Protección CivilMadrid, SpainJuan C. García-Rubira, MDHospital Clínico San CarlosMadrid, SpainJaime García-Prieto, BScDavid Sanz-Rosa, PhDCentro Nacional de Investigaciones CardiovascularesCarlos III (CNIC)Madrid, SpainCarlos Cuellas, MDHospital Universitario LeónLeón, SpainRosana Hernández-Antolín, MDHospital Clínico San CarlosMadrid, SpainAgustín Albarrán, MDHospital Universitario Doce de OctubreMadrid, SpainFelipe Fernández-Vázquez, MDHospital Universitario LeónLeón, SpainJosé M. de la Torre-Hernández, MDHospital Universitario Marqués de ValdecillaSantander, SpainStuart Pocock, PhDGinés Sanz, MDCentro Nacional de Investigaciones CardiovascularesCarlos III (CNIC)Madrid, SpainValentin Fuster, MDThe Zena and Michael A. Wiener CVIMount Sinai School of MedicineNew York, NYDisclosuresNone.References1. 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Chen ZM, Pan HC, Chen YP, Peto R, Collins R, Jiang LX, Xie JX, Liu LS; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.Lancet. 2005; 366:1622–1632.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 15, 2014Vol 130, Issue 3 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.114.009352PMID: 25024129 Originally publishedJuly 15, 2014 PDF download Advertisement SubjectsCoronary Circulation
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