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Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure

Kotecha, Dipak; Flather, Marcus D.; Altman, Douglas G.; Holmes, Jane; Rosano, Giuseppe; Wikstrand, John; Packer, Milton; Coats, Andrew J.S.; Manzano, Luis; Böhm, Michael; van Veldhuisen, Dirk J.; Andersson, Bert; Wedel, Hans; von Lueder, Thomas G.; Rigby, Alan S.; Hjalmarson, Åke; Kjekshus, John; Cleland, John G.F.

Authors

Dipak Kotecha

Marcus D. Flather

Douglas G. Altman

Jane Holmes

Giuseppe Rosano

John Wikstrand

Milton Packer

Andrew J.S. Coats

Luis Manzano

Michael Böhm

Dirk J. van Veldhuisen

Bert Andersson

Hans Wedel

Thomas G. von Lueder

Alan S. Rigby

Åke Hjalmarson

John Kjekshus

John G.F. Cleland



Abstract

Background
The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF).

Objectives
This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo.

Methods
The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization.

Results
A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001).

Conclusions
Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm.

Journal Article Type Article
Publication Date Jun 20, 2017
Print ISSN 0735-1097
Electronic ISSN 1558-3597
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 69
Issue 24
Article Number 24
Pages 2885-2896
APA6 Citation Kotecha, D., Flather, M. D., Altman, D. G., Holmes, J., Rosano, G., Wikstrand, J., …Cleland, J. G. (2017). Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure. Journal of the American College of Cardiology, 69(24), 2885-2896. https://doi.org/10.1016/j.jacc.2017.04.001
DOI https://doi.org/10.1016/j.jacc.2017.04.001
Keywords Atrial fibrillation; Intention-to-treat analysis; Randomized controlled trials
Publisher URL https://www.sciencedirect.com/science/article/pii/S0735109717368936?via%3Dihub
Copyright Statement © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Additional Information This is the accepted manuscript of an article published in Journal of the American college of cardiology, 2017. The version of record is available at the DOI link in this record.

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Copyright Statement
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/





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