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.

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.

Citation

Kotecha, D., Flather, M. D., Altman, D. G., Holmes, J., Rosano, G., Wikstrand, J., Packer, M., Coats, A. J., Manzano, L., Böhm, M., van Veldhuisen, D. J., Andersson, B., Wedel, H., von Lueder, T. G., Rigby, A. S., Hjalmarson, Å., Kjekshus, 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

• Journal Article Type: Article
• Acceptance Date: Apr 2, 2017
• Online Publication Date: Apr 30, 2017
• Publication Date: Jun 20, 2017
• Deposit Date: Mar 3, 2018
• Publicly Available Date: May 1, 2018
• Print ISSN: 0735-1097
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 69
• Issue: 24
• Article Number: 24
• Pages: 2885-2896
• DOI: https://doi.org/10.1016/j.jacc.2017.04.001
• Keywords: Atrial fibrillation; Intention-to-treat analysis; Randomized controlled trials
• Public URL: https://hull-repository.worktribe.com/output/706447
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0735109717368936?via%3Dihub
• 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.
• Contract Date: Mar 3, 2018