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, Marcus D, 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 and Kotecha, Dipak (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. ISSN 0195-668X

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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%.

Item Type:	Article
Uncontrolled Keywords:	heart failure,ejection fraction,beta-blockers,mortality,sinus rhythm,atrial fibrillation
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User:	Pure Connector
Date Deposited:	23 Nov 2017 06:05
Last Modified:	28 Oct 2022 15:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/65544
DOI:	10.1093/eurheartj/ehx564

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