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

Background: Several beta-blockers, with different pharmacological characteristics, are available for heart failure (HF) treatment. We compared Carvedilol (beta 1-beta 2-alpha-blocker), Bisoprolol (beta 1-blocker), and Nebivolol (beta 1-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), O-2/CO2 chemoreceptor sensitivity, constant workload, in normoxia and hypoxia (FiO(2)=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 VO2 was 15.8 +/- 3.6* mL/kg/min (Carvedilol), 16.9 +/- 4.1 (Nebivolol), and 16.9 +/- 3.6 (Bisoprolol). Conclusions: beta-Blockers differently affect several cardiopulmonary functions. Lung diffusion and exercise performance, the former likely due to lower interference with beta 2-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 beta-blocker and a specific HF patient. (C) 2013 Elsevier Ireland Ltd. All rights reserved.