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., …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
• Electronic ISSN: 1522-9645
• 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