title: Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database.
abstract: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens.
  
  
  
  In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P < 0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the β1-/β2-receptor-blocker (n = 2219) vs. β1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5-25 mg, n = 1431) and low dose (<12.5 mg, n = 1960) (HR 1.97, P < 0.001; HR 1.95, P = 0.001, respectively), with no differences between the last two groups (HR 0.84, P = ns).
  
  
  
  In a large population of chronic HFrEF patients, β-blockers were associated with a more favourable prognosis without any difference between β1- and β2-receptor-blockers vs. β1-selective blockers. A better outcome was observed in subjects receiving a high daily dose.
authors.affiliation: IRCCS SDN, Naples, Italy.|Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolillo
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mapelli
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bonomi
authors.affiliation: Division of Cardiac Rehabilitation, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Veruno, Veruno, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Corrà
authors.affiliation: Cardiac Department, Guglielmo da Saliceto Hospital, Piacenza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Piepoli
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.affiliation: Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Gentile
authors.affiliation: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Cassano Murge, Bari, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Lagioia
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Cardiology SUN, Monaldi Hospital (Azienda dei Colli), Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Limongelli
authors.affiliation: Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Sinagra
authors.affiliation: Cardiac Rehabilitation, San Giuseppe Hospital, Multimedica Spa, IRCCS, Milan, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Cattadori
authors.affiliation: Cardiology Division, Santo Spirito Hospital, Rome, Italy.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Scardovi
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carubelli
authors.affiliation: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Cassano Murge, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Scrutino
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology, and Geriatric Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Badagliacca
authors.affiliation: Salvatore Maugeri, Foundation IRCCS, Scientific Institute of Tradate, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Raimondo
authors.affiliation: Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy.|Gabriele Monasterio, Foundation CNR-Regione Toscana, Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.affiliation: Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Magrì
authors.affiliation: Department of Cardiology, University of Foggia, Foggia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Correale
authors.affiliation: Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano, Milan, Italy.|Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Parati
authors.affiliation: Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Caravita
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Spadafora
authors.affiliation: Cardiology Division, Cardiac Arrhythmia Centre and Cardiomyopathies Unit, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Re
authors.affiliation: Section of Cardiology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Cicoira
authors.affiliation: 'A. De Gasperis' Cardio Center, Niguarda Hospital, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Frigerio
authors.affiliation: Cardiac Rehabilitation Unit, Salvatore Maugeri, Foundation, IRCCS, Scientific Institute of Milan, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bussotti
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS - ISMETT, Palermo, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Minà
authors.affiliation: 'A. De Gasperis' Cardio Center, Niguarda Hospital, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Oliva
authors.affiliation: Department of Cardiology, S. Chiara Hospital, Trento, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Battaia
authors.affiliation: Cardiac Rehabilitation, Azienda Ospedali Riuniti, Ancona, Italy.
authors.forename: Romualdo
authors.initials: R
authors.lastname: Belardinelli
authors.affiliation: Division of Cardiac Rehabilitation, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Veruno, Veruno, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mezzani
authors.affiliation: Gabriele Monasterio, Foundation CNR-Regione Toscana, Pisa, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pastormerlo
authors.affiliation: Cardiovascular Center, Health Authority n. 1 and University of Trieste, Trieste, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Lenarda
authors.affiliation: Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy.|Gabriele Monasterio, Foundation CNR-Regione Toscana, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology, and Geriatric Sciences, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Sciomer
authors.affiliation: Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Iorio
authors.affiliation: Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zambon
authors.affiliation: Cardiology University Department, Heart Failure Unit and Cardiopulmonary Laboratory, IRCCS Policlinico San Donato, San Donato, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Guazzi
authors.affiliation: Cardiology SUN, Monaldi Hospital (Azienda dei Colli), Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pacileo
authors.affiliation: Cardiology Division, Santo Spirito Hospital, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ricci
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Contini
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Apostolo
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Palermo
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS - ISMETT, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Clemenza
authors.affiliation: Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marchese
authors.affiliation: Cardiac Department, Guglielmo da Saliceto Hospital, Piacenza, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Binno
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Lombardi
authors.affiliation: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Cassano Murge, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Passantino
authors.affiliation: Department of Advanced Biomedical Sciences, 'Federico II' University of Naples, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone Filardi
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.|Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: Equivalent dose; Heart failure; Prognosis; β-Blocker selectivity; β-Blockers