title: Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial.
abstract: BACKGROUND
  Several β-blockers, with different pharmacological characteristics, are available for heart failure (HF) treatment. We compared Carvedilol (β1-β2-α-blocker), Bisoprolol (β1-blocker), and Nebivolol (β1-blocker, NO-releasing activity).
  
  
  METHODS
  Sixty-one moderate HF patients completed a cross-over randomized trial, receiving, for 2 months each, Carvedilol, Nebivolol, Bisoprolol (25.6 ± 12.6, 5.0 ± 2.4 and 5.0 ± 2.4 mg daily, respectively). At the end of each period, patients underwent: clinical evaluation, laboratory testing, echocardiography, spirometry (including total DLCO and membrane diffusion), O2/CO2 chemoreceptor sensitivity, constant workload, in normoxia and hypoxia (FiO2=16%), and maximal cardiopulmonary exercise test.
  
  
  RESULTS
  No significant differences were observed for clinical evaluation (NYHA classification, Minnesota questionnaire), laboratory findings (including kidney function and BNP), echocardiography, and lung mechanics. DLCO was lower on Carvedilol (18.3 ± 4.8*mL/min/mmHg) compared to Nebivolol (19.9 ± 5.1) and Bisoprolol (20.0 ± 5.0) due to membrane diffusion 20% reduction (*=p<0.0001). Constant workload exercise showed in hypoxia a faster VO2 kinetic and a lower ventilation with Carvedilol. Peripheral and central sensitivity to CO2 was lower in Carvedilol while response to hypoxia was higher in Bisoprolol. Ventilation efficiency (VE/VCO2 slope) was 26.9 ± 4.1* (Carvedilol), 28.8 ± 4.0 (Nebivolol), and 29.0 ± 4.4 (Bisoprolol). Peak VO2 was 15.8 ± 3.6*mL/kg/min (Carvedilol), 16.9 ± 4.1 (Nebivolol), and 16.9 ± 3.6 (Bisoprolol).
  
  
  CONCLUSIONS
  β-Blockers differently affect several cardiopulmonary functions. Lung diffusion and exercise performance, the former likely due to lower interference with β2-mediated alveolar fluid clearance, were higher in Nebivolol and Bisoprolol. On the other hand, Carvedilol allowed a better ventilation efficiency during exercise, likely via a different chemoreceptor modulation. Results from this study represent the basis for identifying the best match between a specific β-blocker and a specific HF patient.
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Contini
authors.forename: Anna
authors.initials: A
authors.lastname: Apostolo
authors.forename: Gaia
authors.initials: G
authors.lastname: Cattadori
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolillo
authors.forename: Annamaria
authors.initials: A
authors.lastname: Iorio
authors.forename: Erika
authors.initials: E
authors.lastname: Bertella
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.forename: Marina
authors.initials: M
authors.lastname: Alimento
authors.forename: Stefania
authors.initials: S
authors.lastname: Farina
authors.forename: Pietro
authors.initials: P
authors.lastname: Palermo
authors.forename: Monica
authors.initials: M
authors.lastname: Loguercio
authors.forename: Valentina
authors.initials: V
authors.lastname: Mantegazza
authors.forename: Marlus
authors.initials: M
authors.lastname: Karsten
authors.forename: Susanna
authors.initials: S
authors.lastname: Sciomer
authors.forename: Damiano
authors.initials: D
authors.lastname: Magrì
authors.forename: Cesare
authors.initials: C
authors.lastname: Fiorentini
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001578:Benzopyrans / Q000008:administration & dosage*; D017298:Bisoprolol / Q000008:administration & dosage*; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004452:Echocardiography; D004562:Electrocardiography; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D010975:Platelet Aggregation Inhibitors; D011412:Propanolamines / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D002227:Carbazoles; D004983:Ethanolamines; D010975:Platelet Aggregation Inhibitors; D011412:Propanolamines; D000068577:Nebivolol; D000077261:Carvedilol; D017298:Bisoprolol
keywords: Chemoreflex; Hypoxia; Ventilation efficiency; β-Blockers