心力衰竭中血管紧张素-脑啡肽酶抑制的肾脏效应及相关结局。
Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure.
机构信息
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII Hospital, Bergamo, Italy.
出版信息
JACC Heart Fail. 2018 Jun;6(6):489-498. doi: 10.1016/j.jchf.2018.02.004. Epub 2018 Apr 11.
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 m 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 m/year; [95% confidence interval: -1.77 to -1.44 ml/min/1.73 m/year] vs. -2.04 ml/min/1.73 m/year [95% CI: -2.21 to -1.88 ml/min/1.73 m/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.
目的
本研究旨在评估沙库巴曲缬沙坦在射血分数降低的心力衰竭患者中的肾脏作用。
背景
射血分数降低的心力衰竭患者的肾功能经常受损，并且在肾素-血管紧张素系统阻断后可能进一步恶化。
方法
在 PARADIGM-HF（沙库巴曲缬沙坦与血管紧张素转换酶抑制剂比较，以评估对心力衰竭患者全球死亡率和发病率的影响）试验中，8399 例射血分数降低的心力衰竭患者被随机分配接受沙库巴曲缬沙坦或依那普利治疗。所有患者均提供估算肾小球滤过率（eGFR），1872 例患者在筛选、随机分组和随访期间的固定时间间隔提供尿白蛋白/肌酐比值（UACR）。我们根据 eGFR 和 UACR 评估研究治疗对 eGFR 和 UACR 变化以及肾脏和心血管结局的影响。
结果
在筛选时，eGFR 为 70±20ml/min/1.73m，2745 例（33%）患者患有慢性肾脏病；中位 UACR 为 1.0mg/mmol（四分位间距[IQR]：0.4 至 3.2mg/mmol），24%患者 UACR 升高。与依那普利相比，沙库巴曲缬沙坦治疗期间 eGFR 的下降幅度较小（-1.61ml/min/1.73m/年；[95%置信区间：-1.77 至-1.44ml/min/1.73m/年] vs. -2.04ml/min/1.73m/年[95%置信区间：-2.21 至-1.88ml/min/1.73m/年]；p<0.001），尽管沙库巴曲缬沙坦比依那普利使 UACR 增加更多（1.20mg/mmol[95%置信区间：1.04 至 1.36mg/mmol] vs. 0.90mg/mmol[95%置信区间：0.77 至 1.03mg/mmol]；p<0.001）。沙库巴曲缬沙坦对心血管死亡或心力衰竭住院的影响不受 eGFR、UACR（p 交互作用=0.70 和 0.34）或 UACR 变化的影响（p 交互作用=0.38）。
结论
与依那普利相比，沙库巴曲缬沙坦导致 eGFR 下降速度较慢，改善了心血管结局，即使在患有慢性肾脏病的患者中也是如此，尽管 UACR 略有增加。
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