Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: The CARNEBI trial

Mauro Contini, Anna Apostolo, Gaia Cattadori, Stefania Paolillo, Annamaria Iorio, Erika Bertella, Elisabetta Salvioni, Marina Alimento, Stefania Farina, Pietro Palermo, Monica Loguercio, Valentina Mantegazza, Marlus Karsten, Susanna Sciomer, Damiano Magrì, Cesare Fiorentini, Piergiuseppe Agostoni

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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/CO 2 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/mm Hg) 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 VO 2 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.

Original languageEnglish
Pages (from-to)2134-2140
Number of pages7
JournalInternational Journal of Cardiology
Volume168
Issue number3
DOIs
Publication statusPublished - Oct 3 2013

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Nebivolol
Bisoprolol
Heart Failure
Ventilation
Exercise
Workload
Echocardiography
Lung
Membranes
carvedilol
Spirometry
Carbon Monoxide
Mechanics
Exercise Test
Cross-Over Studies

Keywords

  • β-Blockers
  • Chemoreflex
  • Hypoxia
  • Ventilation efficiency

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

@article{bb8f4e579a5a481f9a3179ec00644b27,
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/CO 2 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/mm Hg) 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 VO 2 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.",
keywords = "β-Blockers, Chemoreflex, Hypoxia, Ventilation efficiency",
author = "Mauro Contini and Anna Apostolo and Gaia Cattadori and Stefania Paolillo and Annamaria Iorio and Erika Bertella and Elisabetta Salvioni and Marina Alimento and Stefania Farina and Pietro Palermo and Monica Loguercio and Valentina Mantegazza and Marlus Karsten and Susanna Sciomer and Damiano Magr{\`i} and Cesare Fiorentini and Piergiuseppe Agostoni",
year = "2013",
month = "10",
day = "3",
doi = "10.1016/j.ijcard.2013.01.277",
language = "English",
volume = "168",
pages = "2134--2140",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure

T2 - The CARNEBI trial

AU - Contini, Mauro

AU - Apostolo, Anna

AU - Cattadori, Gaia

AU - Paolillo, Stefania

AU - Iorio, Annamaria

AU - Bertella, Erika

AU - Salvioni, Elisabetta

AU - Alimento, Marina

AU - Farina, Stefania

AU - Palermo, Pietro

AU - Loguercio, Monica

AU - Mantegazza, Valentina

AU - Karsten, Marlus

AU - Sciomer, Susanna

AU - Magrì, Damiano

AU - Fiorentini, Cesare

AU - Agostoni, Piergiuseppe

PY - 2013/10/3

Y1 - 2013/10/3

N2 - 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/CO 2 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/mm Hg) 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 VO 2 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.

AB - 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/CO 2 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/mm Hg) 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 VO 2 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.

KW - β-Blockers

KW - Chemoreflex

KW - Hypoxia

KW - Ventilation efficiency

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U2 - 10.1016/j.ijcard.2013.01.277

DO - 10.1016/j.ijcard.2013.01.277

M3 - Article

C2 - 23506636

AN - SCOPUS:84885664974

VL - 168

SP - 2134

EP - 2140

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

IS - 3

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