Dipak Kotecha1, Marcus D Flather2, Douglas G Altman3, Jane Holmes3, Giuseppe Rosano4, John Wikstrand5, Milton Packer6, Andrew J S Coats7, Luis Manzano8, Michael Böhm9, Dirk J van Veldhuisen10, Bert Andersson11, Hans Wedel12, Thomas G von Lueder13, Alan S Rigby14, Åke Hjalmarson11, John Kjekshus15, John G F Cleland16. 1. University of Birmingham Institute of Cardiovascular Sciences, Birmingham, United Kingdom; Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Victoria, Australia. 2. Norwich Medical School, University of East Anglia, Norwich, United Kingdom. 3. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. 4. Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy; Cardiovascular and Cell Science Institute, St. George's University of London, London, United Kingdom. 5. Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 6. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas. 7. Monash University, Melbourne, Victoria, Australia; University of Warwick, Warwick, United Kingdom. 8. Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain. 9. Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. 10. Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. 11. Department of Cardiology, Sahlgrenska University Hospital and Gothenburg University, Gothenburg, Sweden. 12. Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 13. Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Victoria, Australia; Department of Cardiology, Oslo University Hospital, Oslo, Norway. 14. Academic Cardiology, Castle Hill Hospital, Kingston upon Hull, United Kingdom. 15. Rikshospitalet University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway. 16. Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, United Kingdom. Electronic address: john.cleland@glasgow.ac.uk.
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.
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.
Authors: Alexey V Zaitsev; Natalia S Torres; Keiko M Cawley; Amira D Sabry; Junco S Warren; Mark Warren Journal: Am J Physiol Heart Circ Physiol Date: 2019-03-15 Impact factor: 4.733
Authors: Dipak Kotecha; Karina V Bunting; Simrat K Gill; Samir Mehta; Mary Stanbury; Jacqueline C Jones; Sandra Haynes; Melanie J Calvert; Jonathan J Deeks; Richard P Steeds; Victoria Y Strauss; Kazem Rahimi; A John Camm; Michael Griffith; Gregory Y H Lip; Jonathan N Townend; Paulus Kirchhof Journal: JAMA Date: 2020-12-22 Impact factor: 56.272
Authors: Felix Hohendanner; F R Heinzel; F Blaschke; B M Pieske; W Haverkamp; H L Boldt; A S Parwani Journal: Heart Fail Rev Date: 2018-01 Impact factor: 4.214