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

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

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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.
Original languageEnglish
Pages (from-to)2885–2896
Number of pages12
JournalJournal of the American College of Cardiology
Issue number24
Early online date30 Apr 2017
Publication statusPublished - 20 Jun 2017


  • Heart failure
  • Heart rate
  • Beta-blockers
  • Atrial fibrillation
  • Individual-Patient-Data-Meta-Analysis

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