Heart rate, heart rhythm and prognostic benefits of beta-blockers in heart failure: individual patient-data meta-analysis

Kotecha, D. et al. (2017) Heart rate, heart rhythm and prognostic benefits of beta-blockers in heart failure: individual patient-data meta-analysis. Journal of the American College of Cardiology, 69(24), pp. 2885-2896. (doi: 10.1016/j.jacc.2017.04.001) (PMID:28467883)

Abstract

Background: The relationship between mortality and heart rate remains unclear for patients with heart failure and reduced ejection fraction (HFrEF) in either sinus rhythm or atrial fibrillation (AF). Objective: To investigate the prognostic importance of heart rate in HFrEF in randomized controlled trials (RCTs) comparing beta-blockers and placebo. Methods: The Beta-blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual-patient data from eleven double-blind RCTs. The primary outcome was all-cause mortality, analysed with Cox proportional hazard ratios (HR) modelling heart rate measured at baseline and approximately six-months post-randomization. Results: A higher heart rate at baseline was associated with greater all-cause mortality in patients with sinus rhythm (n=14,166; adjusted HR 1.11 per 10 beats/minute; 95% CI 1.07-1.15, p<0.0001), but not in AF (n=3,034; HR 1.03 per 10 beats/minute; 0.97-1.08, p=0.38). Beta-blockers reduced ventricular rate by 12 beats/minute in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomised to beta-blockers (HR 0.73 versus placebo, 95% CI 0.67-0.79; 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 0.81-1.12; 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/minute increase, 95% CI 1.11-1.22; p<0.0001). Conclusions: Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with HFrEF in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Kotecha, D., Flather, M. D., Altman, D. G., Holmes, J., Rosano, G., Wikstrand, J., Packer, M., Coats, A. J.S., Manzano, L., Böhm, M., van Veldhuisen, D. J., Andersson, B., Wedel, H., von Lueder, T. G., Rigby, A. S., Hjalmarson, Å., Kjekshus, J., and Cleland, J. G.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Journal of the American College of Cardiology
• Publisher: Elsevier
• ISSN: 0735-1097
• ISSN (Online): 1558-3597
• Published Online: 30 April 2017
• Copyright Holders: Copyright © 2017 The American College of Cardiology Foundation
• First Published: First published in Journal of the American College of Cardiology 69(24):2885-2896
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher