University of Birmingham Impact of renal impairment on beta-blocker efficacy in patients with heart failure

ISS Fro cu Fa Nu Kin Ins Pis Sa W D Ca Un 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 m; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m. 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 m 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 m (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m (95% CI: 0.58 to 0.87; p 1⁄4 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 m) 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. (J Am Coll Cardiol 2019;74: 2893–904) © 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). N 0735-1097 https://doi.org/10.1016/j.jacc.2019.09.059 m the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Cardiovaslar Research and Education in Therapeutics, Monash University, Melbourne, Victoria, Australia; Norwich Medical School, culty of Medicine and Health Science, University of East Anglia, Norwich, United Kingdom; Centre for Statistics in Medicine, ffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United gdom; Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas; Cardiovascular and Cell Science titute, St. George’s University of London, London, United Kingdom; Department of Medical Sciences, IRCCS San Raffaele ana, Roma, Italy; Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Homburg/ ar, Germany; Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, United Kingdom; allenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; epartment of Cardiology, Charite Campus Virchow-Klinikum, Berlin, Germany; University of Groningen, Department of rdiology, University Medical Centre Groningen, RB Groningen, the Netherlands; Internal Medicine Department, Hospital iversitario Ramón y Cajal, Universidad de Alcalá (IRYCIS), Plaza de San Diego, Madrid, Spain; Department of Cardiology, Oslo SEE PAGE 2905 ABBR EV I A T I ON S