J Wikstrand1, H Wedel, D Castagno, J J V McMurray. 1. Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Abstract
AIMS: The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. METHODS: We compared stratified (s ) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) ≤ 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age ≥ 70 years and EF ≤ 35%). RESULTS: The annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii) SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P = 0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. CONCLUSION: The efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated.
RCT Entities:
AIMS: The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. METHODS: We compared stratified (s ) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) ≤ 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age ≥ 70 years and EF ≤ 35%). RESULTS: The annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii) SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P = 0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. CONCLUSION: The efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated.
Authors: David A Sykes; Mireia Jiménez-Rosés; John Reilly; Robin A Fairhurst; Steven J Charlton; Dmitry B Veprintsev Journal: Pharmacol Res Perspect Date: 2022-08
Authors: Hanna Fröhlich; Lorella Torres; Tobias Täger; Dieter Schellberg; Anna Corletto; Syed Kazmi; Kevin Goode; Morten Grundtvig; Torstein Hole; Hugo A Katus; John G F Cleland; Dan Atar; Andrew L Clark; Stefan Agewall; Lutz Frankenstein Journal: Clin Res Cardiol Date: 2017-04-22 Impact factor: 5.460
Authors: Ewan D Fowler; Mark J Drinkhill; Ruth Norman; Eleftheria Pervolaraki; Rachel Stones; Emma Steer; David Benoist; Derek S Steele; Sarah C Calaghan; Ed White Journal: J Mol Cell Cardiol Date: 2018-05-26 Impact factor: 5.000
Authors: Pardeep S Jhund; Michael Fu; Edmundo Bayram; Chen-Huan Chen; Marta Negrusz-Kawecka; Arvo Rosenthal; Akshay S Desai; Martin P Lefkowitz; Adel R Rizkala; Jean L Rouleau; Victor C Shi; Scott D Solomon; Karl Swedberg; Michael R Zile; John J V McMurray; Milton Packer Journal: Eur Heart J Date: 2015-07-31 Impact factor: 29.983
Authors: Quinn S Wells; Eric Farber-Eger; Loren Lipworth; Paul Dluzniewski; Ricardo Dent; John Umeijiego; Sarah S Cohen Journal: Clin Epidemiol Date: 2022-01-13 Impact factor: 4.790