Dipak Kotecha1, Simrat K Gill2, Marcus D Flather3, Jane Holmes4, Milton Packer5, Giuseppe Rosano6, Michael Böhm7, John J V McMurray8, John Wikstrand9, Stefan D Anker10, Dirk J van Veldhuisen11, Luis Manzano12, Thomas G von Lueder13, Alan S Rigby14, Bert Andersson15, John Kjekshus16, Hans Wedel17, Frank Ruschitzka18, John G F Cleland19, Kevin Damman11, Josep Redon20, Andrew J S Coats6. 1. Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Victoria, Australia. Electronic address: d.kotecha@bham.ac.uk. 2. Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom. 3. Norwich Medical School, Faculty of Medicine and Health Science, University of East Anglia, Norwich, United Kingdom. 4. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. 5. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas. 6. Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy. 7. Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Homburg/Saar, Germany. 8. Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, United Kingdom. 9. Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 10. Department of Cardiology, Charite Campus Virchow-Klinikum, Berlin, Germany. 11. University of Groningen, Department of Cardiology, University Medical Centre Groningen, RB Groningen, the Netherlands. 12. Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá (IRYCIS), Plaza de San Diego, Madrid, Spain. 13. Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Victoria, Australia; Department of Cardiology, Oslo University Hospital, Oslo, Norway. 14. Hull York Medical School, Faculty of Health Sciences, University of Hull, Kingston-upon-Hull, United Kingdom. 15. Department of Cardiology, Sahlgrenska University Hospital and Gothenburg University, Gothenburg, Sweden. 16. Rikshospitalet University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway. 17. Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 18. Klinik fur Kardiologie, UniversitätsSpital Zürich, Zürich, Switzerland. 19. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. 20. INCLIVA Biomedical Research Institute, Valencia, Spain.
Abstract
BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS:Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS:Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.
RCT Entities:
BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficientpatients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS:Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.
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
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Authors: Pardeep S Jhund; Scott D Solomon; Kieran F Docherty; Hiddo J L Heerspink; Inder S Anand; Michael Böhm; Vijay Chopra; Rudolf A de Boer; Akshay S Desai; Junbo Ge; Masafumi Kitakaze; Bela Merkley; Eileen O'Meara; Morten Shou; Sergey Tereshchenko; Subodh Verma; Pham Nguyen Vinh; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Olof Bengtsson; Anna Maria Langkilde; Mikaela Sjöstrand; John J V McMurray Journal: Circulation Date: 2020-10-12 Impact factor: 29.690
Authors: Andreas Karwath; Karina V Bunting; Simrat K Gill; Otilia Tica; Samantha Pendleton; Furqan Aziz; Andrey D Barsky; Saisakul Chernbumroong; Jinming Duan; Alastair R Mobley; Victor Roth Cardoso; Luke Slater; John A Williams; Emma-Jane Bruce; Xiaoxia Wang; Marcus D Flather; Andrew J S Coats; Georgios V Gkoutos; Dipak Kotecha Journal: Lancet Date: 2021-08-30 Impact factor: 79.321