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Review
. 2017 Jun 20;69(24):2885-2896.
doi: 10.1016/j.jacc.2017.04.001. Epub 2017 Apr 30.

Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure

Dipak Kotecha  1 , Marcus D Flather  2 , Douglas G Altman  3 , Jane Holmes  3 , Giuseppe Rosano  4 , John Wikstrand  5 , Milton Packer  6 , Andrew J S Coats  7 , Luis Manzano  8 , Michael Böhm  9 , Dirk J van Veldhuisen  10 , Bert Andersson  11 , Hans Wedel  12 , Thomas G von Lueder  13 , Alan S Rigby  14 , Åke Hjalmarson  11 , John Kjekshus  15 , John G F Cleland  16 ; Beta-Blockers in Heart Failure Collaborative Group
Affiliations
Free article
Review

Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure

Dipak Kotecha et al. J Am Coll Cardiol. .
Free article

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.

Keywords: atrial fibrillation; intention-to-treat analysis; randomized controlled trials.

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Comment in

  • How to Use Beta-Blockers in Heart Failure With Reduced Ejection Fraction and Atrial Fibrillation.
    Filippatos G, Farmakis D. Filippatos G, et al. J Am Coll Cardiol. 2017 Jun 20;69(24):2897-2900. doi: 10.1016/j.jacc.2017.04.049. J Am Coll Cardiol. 2017. PMID: 28619188 No abstract available.
  • An Incomplete Story.
    Reiffel JA. Reiffel JA. J Am Coll Cardiol. 2018 Jan 2;71(1):104. doi: 10.1016/j.jacc.2017.07.803. J Am Coll Cardiol. 2018. PMID: 29301618 No abstract available.
  • Reply: An Incomplete Story.
    Cleland JGF, Flather MD, Altman DG, Kotecha D; Beta-Blockers in Heart Failure Collaborative Group. Cleland JGF, et al. J Am Coll Cardiol. 2018 Jan 2;71(1):105. doi: 10.1016/j.jacc.2017.10.078. J Am Coll Cardiol. 2018. PMID: 29301619 No abstract available.

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