Kevin Damman1, Mauro Gori2, Brian Claggett3, Pardeep S Jhund4, Michele Senni5, Martin P Lefkowitz6, Margaret F Prescott6, Victor C Shi6, Jean L Rouleau7, Karl Swedberg8, Michael R Zile9, Milton Packer10, Akshay S Desai3, Scott D Solomon3, John J V McMurray11. 1. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII Hospital, Bergamo, Italy. 3. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 4. British Heart Foundation (BHF) Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. 5. Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII Hospital, Bergamo, Italy. 6. Novartis Pharmaceuticals, East Hanover, New Jersey. 7. Institut de Cardiologie de Montréal, Université de Montréal, Montreal, Canada. 8. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; National Heart and Lung Institute, Imperial College London, London, United Kingdom. 9. Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina. 10. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas. 11. British Heart Foundation (BHF) Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: John.McMurray@glasgow.ac.uk.
Abstract
OBJECTIVES: The purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction. BACKGROUND:Renal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate further after blockade of the renin-angiotensin system. METHODS: In the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, 8,399 patients with heart failure with reduced ejection fraction were randomized to treatment with sacubitril/valsartan or enalapril. The estimated glomerular filtration rate (eGFR) was available for all patients, and the urinary albumin/creatinine ratio (UACR) was available in 1872 patients, at screening, randomization, and at fixed time intervals during follow-up. We evaluated the effect of study treatment on change in eGFR and UACR, and on renal and cardiovascular outcomes, according to eGFR and UACR. RESULTS: At screening, the eGFR was 70 ± 20 ml/min/1.73 m2 and 2,745 patients (33%) had chronic kidney disease; the median UACR was 1.0 mg/mmol (interquartile range [IQR]: 0.4 to 3.2 mg/mmol) and 24% had an increased UACR. The decrease in eGFR during follow-up was less with sacubitril/valsartan compared with enalapril (-1.61 ml/min/1.73 m2/year; [95% confidence interval: -1.77 to -1.44 ml/min/1.73 m2/year] vs. -2.04 ml/min/1.73 m2/year [95% CI: -2.21 to -1.88 ml/min/1.73 m2/year ]; p < 0.001) despite a greater increase in UACR with sacubitril/valsartan than with enalapril (1.20 mg/mmol [95% CI: 1.04 to 1.36 mg/mmol] vs. 0.90 mg/mmol [95% CI: 0.77 to 1.03 mg/mmol]; p < 0.001). The effect of sacubitril/valsartan on cardiovascular death or heart failure hospitalization was not modified by eGFR, UACR (p interaction = 0.70 and 0.34, respectively), or by change in UACR (p interaction = 0.38). CONCLUSIONS: Compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the eGFR and improved cardiovascular outcomes, even in patients with chronic kidney disease, despite causing a modest increase in UACR.
RCT Entities:
OBJECTIVES: The purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction. BACKGROUND: Renal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate further after blockade of the renin-angiotensin system. METHODS: In the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, 8,399 patients with heart failure with reduced ejection fraction were randomized to treatment with sacubitril/valsartan or enalapril. The estimated glomerular filtration rate (eGFR) was available for all patients, and the urinary albumin/creatinine ratio (UACR) was available in 1872 patients, at screening, randomization, and at fixed time intervals during follow-up. We evaluated the effect of study treatment on change in eGFR and UACR, and on renal and cardiovascular outcomes, according to eGFR and UACR. RESULTS: At screening, the eGFR was 70 ± 20 ml/min/1.73 m2 and 2,745 patients (33%) had chronic kidney disease; the median UACR was 1.0 mg/mmol (interquartile range [IQR]: 0.4 to 3.2 mg/mmol) and 24% had an increased UACR. The decrease in eGFR during follow-up was less with sacubitril/valsartan compared with enalapril (-1.61 ml/min/1.73 m2/year; [95% confidence interval: -1.77 to -1.44 ml/min/1.73 m2/year] vs. -2.04 ml/min/1.73 m2/year [95% CI: -2.21 to -1.88 ml/min/1.73 m2/year ]; p < 0.001) despite a greater increase in UACR with sacubitril/valsartan than with enalapril (1.20 mg/mmol [95% CI: 1.04 to 1.36 mg/mmol] vs. 0.90 mg/mmol [95% CI: 0.77 to 1.03 mg/mmol]; p < 0.001). The effect of sacubitril/valsartan on cardiovascular death or heart failure hospitalization was not modified by eGFR, UACR (p interaction = 0.70 and 0.34, respectively), or by change in UACR (p interaction = 0.38). CONCLUSIONS: Compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the eGFR and improved cardiovascular outcomes, even in patients with chronic kidney disease, despite causing a modest increase in UACR.
Authors: Roberto Ferrari; J Cardoso; M C Fonseca; C Aguiar; J I Moreira; A Fucili; C Rapezzi Journal: Clin Res Cardiol Date: 2019-09-17 Impact factor: 5.460
Authors: Aaron M Hein; Julia J Scialla; Daniel Edmonston; Lauren B Cooper; Adam D DeVore; Robert J Mentz Journal: JACC Heart Fail Date: 2019-05 Impact factor: 12.035