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 and Cleland, John G. F. (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. ISSN 0735-1097

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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: Article
Uncontrolled Keywords: heart failure,heart rate,beta-blockers,atrial fibrillation,individual-patient-data-meta-analysis
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)
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Depositing User: Pure Connector
Date Deposited: 16 May 2017 05:05
Last Modified: 11 Jul 2023 09:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/63525
DOI: 10.1016/j.jacc.2017.04.001


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