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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


Alan S. Rigby


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; 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 <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%.

Journal Article Type Article
Publication Date Jan 1, 2018
Journal European heart journal
Print ISSN 0195-668X
Electronic ISSN 1522-9645
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 39
Issue 1
Pages 26-35
Keywords Heart failure; Ejection fraction; Beta-blockers; Mortality; Sinus rhythm; Atrial fibrillation
Publisher URL


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