Multiparametric comparison of CARvedilol,vs. NEbivolol,vs. BIsoprolol in moderate heart failure: The CARNEBI trial |
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| Authors: | 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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| Institution: | 1. Centro Cardiologico Monzino, IRCCS, Milan, Italy;2. Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy;3. Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy;4. Laboratório de Fisioterapia Cardiovascular, Núcleo de Pesquisa em Exercício Físico, Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP, Brazil;5. Dipartimento di Scienze Cardiovascolari e Respiratorie, “Sapienza”, Rome University, Rome, Italy;6. Dipartimento di Medicina Clinica e Molecolare, S. Andrea Hospital, “Sapienza”, Rome University, Rome, Italy;g Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy;h Division of Pulmonary and Critical Care and Medicine, Department of Medicine, University of Washington, Seattle, WA, United States |
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| Abstract: | BackgroundSeveral 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).MethodsSixty-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.ResultsNo 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 VO2 was 15.8 ± 3.6* mL/kg/min (Carvedilol), 16.9 ± 4.1 (Nebivolol), and 16.9 ± 3.6 (Bisoprolol).Conclusionsβ-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. |
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| Keywords: | β-Blockers Ventilation efficiency Hypoxia Chemoreflex |
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