Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure
Kotecha, Dipak; Flather, M.; Altman, Douglas G.; Holmes, Jane; Rosano, Giuseppe; Wikstrand, John; Packer, Milton; Coats, Andrew J. S.; Manzano Espinosa, Luis; Böhm, M. (Michael), 1958-; Veldhuisen, D.J. van (Dirk Jan), 1959-; Andersson, Bert, 1952-; Wedel, Hans, 1940-; Von Lueder, Thomas G., 1968-; Rigby, Alan S.; Hjalmarson, Åke; Kjekshus, John; Cleland, John G. F.
Hull York Medical School
Heart failure; Heart rate; Beta-blockers; Atrial fibrillation; Individual-Patient-Data-Meta-Analysis
- ©2018, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
- Alternative title
- Heart rate, heart rhythm and prognostic benefits of beta-blockers in heart failure : individual patient-data meta-analysis
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.
- The University of Hull
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- Journal of the American college of cardiology
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Authors' accepted manuscript of article published in: Journal of the American college of cardiology, 2017, v.69, issue 24.
- Published article