Review article

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

John G.F. ClelandRobertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, University Avenue, Glasgow G12 8QQ, UKKarina V BuntingInstitute of Cardiovascular Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UKMarcus FlatherNorwich Medical School, Faculty of Medicine and Health Science, University of East Anglia, Norwich NR4 7TJ, UKDouglas G. AltmanCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX1 2JD, UKJane HolmesCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX1 2JD, UKAndrew J.S. CoatsLuís ManzanoInternal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá (IRYCIS), Plaza de San Diego, 28801 Alcalá de Henares, Madrid, SpainJohn J.V. McMurrayInstitute of Cardiovascular and Medical Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UKFrank RuschitzkaDirk J. van VeldhuisenDepartment of Cardiology, University Medical Centre Groningen, University of Groningen, PO box 30.001 9700 RB Groningen, The NetherlandsThomas G. von LuederCentre of Cardiovascular Research and Education in Therapeutics, Monash University, 99 Commercial Road, Melbourne, Victoria 3004, AustraliaMichael BöhmKardiologie, Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Str. 100, 66421 Homburg/Saar, GermanyBert AnderssonDepartment of Cardiology, Sahlgrenska University Hospital and Gothenburg University, Blå stråket 5, 413 45 Gothenburg, SwedenJohn KjekshusRikshospitalet University Hospital and Faculty of Medicine, University of Oslo, Problemveien 7, 0315 Oslo, NorwayMilton PackerBaylor Heart and Vascular Institute, Baylor University Medical Center, 621 Hall St, Dallas TX 75226, USAAlan S. RigbyHull York Medical School, Faculty of Health Sciences, University of Hull, Kingston-upon-Hull, HU6 7RX, UKGiuseppe RosanoCardiovascular and Cell Science Institute, St George’s University of London, SW17 0RE, UKHans WedelHealth Metrics, Sahlgrenska Academy, University of Gothenburg, Box 100, S-405 30 Gothenburg, SwedenÅke HjalmarsonDepartment of Cardiology, Sahlgrenska University Hospital and Gothenburg University, Blå stråket 5, 413 45 Gothenburg, SwedenJohn WikstrandWallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Bruna Stråket 16, 413 45 Gothenburg, SwedenDipak KotechaCentre of Cardiovascular Research and Education in Therapeutics, Monash University, 99 Commercial Road, Melbourne, Victoria 3004, AustraliaBeta-blockers in Heart Failure Collaborative Group

2017en

ABI

Abstract

Aims: 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 (Clinicaltrials.gov: 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. Conclusion: 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%.

Identifiers

DOI: 10.1093/eurheartj/ehx564

Citations and references

Cited by 20 references

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