Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care (P.C.S., J.B., J.W., P.A., F.H., S.G., S.M.-W.), Friedrich-Schiller-University, University Hospital Jena, Germany.
Department of Cardiology and Pneumology, Georg-August-University, University Medical Centre Göttingen, Germany (S.v.H.).
Circulation. 2022 Jul 26;146(4):289-298. doi: 10.1161/CIRCULATIONAHA.122.059038. Epub 2022 Jun 29.
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.
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).
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]; =0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; =0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; =0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; =0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; =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]; <0.001). There were no differences in the incidence of safety events between groups.
Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure.
URL: https://www.
gov; Unique identifier: NCT04049045.
在急性失代偿性心力衰竭患者中，使用袢利尿剂的有效利尿方案通常受到肾功能恶化的限制。钠-葡萄糖共转运蛋白-2 抑制剂可在稳定型心力衰竭患者中诱导糖尿和钠排泄，并具有肾脏保护作用，但在急性失代偿性心力衰竭中的作用尚不清楚。
在这项单中心、前瞻性、双盲、安慰剂对照、随机研究中，我们将急性失代偿性心力衰竭患者随机分配至每日服用恩格列净 25mg 或安慰剂，同时接受包括袢利尿剂在内的标准利尿剂治疗。主要终点为 5 天内的累积尿量。次要终点包括利尿剂效率、肾功能和损伤标志物的动态变化以及 NT-proBNP（N 端脑利钠肽前体）。
在急性失代偿性心力衰竭住院后 12 小时内，有 60 名患者被随机分配。与标准的急性失代偿性心力衰竭治疗相比，每日加用恩格列净可使 5 天内的累积尿量增加 25%（中位数：安慰剂组为 10.8 升 mL，恩格列净组为 8.7 升 mL，组间差异估计为 2.2 升 [95%CI，8.4 至 3.6]；=0.003）。与安慰剂相比，恩格列净增加了利尿剂效率（呋塞米等效物每毫克 14.1 毫升尿液[95%CI，0.6 至 27.7]；=0.041），而不影响肾功能标志物（估计肾小球滤过率，51±19 与 54±17 毫升/分钟/1.73 平方米；=0.599）或损伤标志物（总尿蛋白，492±845 与 503±847 毫克/克肌酐；=0.975；和尿α1-微球蛋白，55.4±38.6 与 31.3±33.6 毫克/克肌酐；=0.066），与安慰剂相比，恩格列净组的 NT-proBNP 下降更为明显（5 天后分别为-1861 与-727.2 pg/mL；斜率商，0.89 [95%CI，0.83 至 0.95]；<0.001）。两组的安全性事件发生率无差异。
在急性失代偿性心力衰竭患者中，早期加用恩格列净联合标准利尿剂治疗可增加尿量，而不影响肾功能。
