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

Cleland, John G.F.; Bunting, Karina V.; Flather, M.; Altman, Douglas G.; Holmes, Jane; Coats, Andrew J.S.; Manzano, Luis; McMurray, John J.V.; Ruschitzka, Frank; van Veldhuisen, Dirk J.; Von Lueder, Thomas G.; Böhm, Michael; Andersson, Bert; Kjekshus, John; Packer, Milton; Rigby, Alan S.; Rosano, Giuseppe; Wedel, Hans; Hjalmarson, Åke; Wikstrand, John; Kotecha, Dipak; Beta-blockers in Heart Failure Collaborative Group

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, randomised, placebo-controlled trials. Methods and Results: Individual patient data meta-analysis of eleven trials, stratified by baseline LVEF and heart rhythm (Clinical trials.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%] randomised to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 (95% 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 randomisation, LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50% (n=4,601). For patients in atrial fibrillation at baseline (n=3,050), beta-blockers increased LVEF when

Citation

Cleland, J. G., Bunting, K. V., Flather, M., Altman, D. G., Holmes, J., Coats, A. J., Manzano, L., McMurray, J. J., Ruschitzka, F., van Veldhuisen, D. J., Von Lueder, T. G., Böhm, M., Andersson, B., Kjekshus, J., Packer, M., Rigby, A. S., Rosano, G., Wedel, H., Hjalmarson, Å., Wikstrand, J., …Beta-blockers in Heart Failure Collaborative Group. (2018). Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: An individual patient-level analysis of double-blind randomized trials. European Heart Journal, 39(1), 26-35. https://doi.org/10.1093/eurheartj/ehx564

• Journal Article Type: Article
• Acceptance Date: Sep 15, 2017
• Online Publication Date: Oct 10, 2017
• Publication Date: Jan 1, 2018
• Deposit Date: Sep 18, 2017
• Publicly Available Date: Oct 10, 2018
• Journal: European heart journal
• Print ISSN: 0195-668X
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Issue: 1
• Pages: 26-35
• DOI: https://doi.org/10.1093/eurheartj/ehx564
• Keywords: Heart failure; Ejection fraction; Beta-blockers; Mortality; Sinus rhythm; Atrial fibrillation
• Public URL: https://hull-repository.worktribe.com/output/454868
• Publisher URL: https://academic.oup.com/eurheartj/article/4430343
• Contract Date: Sep 18, 2017