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Eur Heart J. 2018 Jan 1;39(1):26-35. doi: 10.1093/eurheartj/ehx564.

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.

Author information

Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Institute of Cardiovascular Sciences, University of Birmingham, Vincent Drive, Birmingham B15?2TT, UK.
Norwich Medical School, Faculty of Medicine and Health Science, University of East Anglia, Norwich NR4 7TJ, UK.
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX1 2JD, UK.
San Raffaele Pisana Scientific Institute, Via della Pisana, 235, 00163 Rome, Italy.
Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá (IRYCIS), Plaza de San Diego, 28801 Alcalá de Henares, Madrid, Spain.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Klinik für Kardiologie, UniversitätsSpital Zürich, Universitätstrasse 8, 8006 Zürich, Switzerland.
Department of Cardiology, University Medical Centre Groningen, University of Groningen, PO box 30.001 9700 RB Groningen, The Netherlands.
Department of Cardiology, Oslo University Hospital, PO Box 4950 Nydalen N-0424 Oslo, Norway.
Centre of Cardiovascular Research and Education in Therapeutics, Monash University, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Kardiologie, Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Str. 100, 66421 Homburg/Saar, Germany.
Department of Cardiology, Sahlgrenska University Hospital and Gothenburg University, Blå stråket 5, 413 45 Gothenburg, Sweden.
Rikshospitalet University Hospital and Faculty of Medicine, University of Oslo, Problemveien 7, 0315 Oslo, Norway.
Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 Hall St, Dallas TX 75226, USA.
Hull York Medical School, Faculty of Health Sciences, University of Hull, Kingston-upon-Hull, HU6 7RX, UK.
Cardiovascular and Cell Science Institute, St George's University of London, SW17 0RE, UK.
Department of Medical Sciences, IRCCS San Raffaele Pisana, Via della Pisana, 235, 00163 Roma, Italy.
Health Metrics, Sahlgrenska Academy, University of Gothenburg, Box 100, S-405 30 Gothenburg, Sweden.
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Bruna Stråket 16, 413 45 Gothenburg, Sweden.
Institute of Cardiovascular Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.



Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials.

Methods and results:

Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm ( NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis.


Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.


Atrial fibrillation; Beta-blockers; Ejection fraction; Heart failure; Mortality; Sinus rhythm

[Available on 2019-01-01]
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