Background:Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear.Methods:In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).Results:Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6–27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P=0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P=0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (−1861 versus −727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83–0.95]; P<0.001). There were no differences in the incidence of safety events between groups.Conclusions:Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04049045.

中文翻译：

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早期恩格列净治疗对急性失代偿性心力衰竭 (EMPAG-HF) 患者利尿和肾功能的影响

背景：对于急性失代偿性心力衰竭患者，使用袢利尿剂进行有效的利尿治疗往往会受到肾功能恶化的限制。钠-葡萄糖协同转运蛋白 2 抑制剂可诱导糖尿和钠排泄，对稳定型心力衰竭患者具有肾保护作用，但其在急性失代偿性心力衰竭中的作用尚不清楚。方法：在这项单中心、前瞻性、双盲、安慰剂对照的研究中，在随机研究中，除了包括袢利尿剂在内的标准减充血治疗外，我们将急性失代偿性心力衰竭患者随机分配至每日 25 毫克恩格列净或安慰剂组。主要终点是 5 天内的累积尿量。次要终点包括利尿效率、肾功能和损伤标志物动态以及 NT-proBNP（N 末端 B 型钠尿肽前体）。 结果：60 名患者因急性失代偿性心力衰竭住院 12 小时内被随机分组​​。在急性失代偿性心力衰竭的标准药物治疗中每日添加恩格列净，导致 5 天内累积尿量增加 25%（中位数为 10.8 L·mL，安慰剂为 8.7 L·mL，组间差异估计为 2.2 L [95% CI，8.4 至 3.6] ；P =0.003）。与安慰剂相比，恩格列净提高了利尿效率（每毫克呋塞米当量 14.1 mL 尿液 [95% CI，0.6–27.7]；P = 0.041），且不影响肾功能标志物（估计肾小球滤过率，51±19 vs 54±17 mL/每 1.73 平方米分钟；P = 0.599）或损伤（总尿蛋白，492±845 与 503±847 mg/g 肌酐；P = 0.975；尿 α1-微球蛋白，55.4±38.6 与 31.3±33.6 mg/g 肌酐；P = 0.066），与安慰剂相比，恩格列净组 NT-proBNP 下降更明显（5 天后 -1861 与 -727.2 pg/mL；斜率商，0.89 [95% CI，0.83–0.95]；P < 0.001 ）。各组之间安全事件的发生率没有差异。结论：在标准利尿治疗中早期添加恩格列净可增加急性失代偿性心力衰竭患者的尿量，而不影响肾功能。注册：URL：https://www.clinicaltrials。政府；唯一标识符：NCT04049045。