Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France (F.Z., J.P.F.).
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK (S.J.P.).
Circulation. 2021 Jan 26;143(4):310-321. doi: 10.1161/CIRCULATIONAHA.120.051685. Epub 2020 Oct 23.
In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin reduced cardiovascular death or heart failure (HF) hospitalization and total HF hospitalizations, and slowed the progressive decline in kidney function in patients with HF and a reduced ejection fraction, with and without diabetes. We aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function.
In this prespecified analysis, patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m or albumin-to-creatine ratio >300 mg/g). The primary and key secondary outcomes were: (1) a composite of cardiovascular death or HF hospitalization (primary outcome); (2) total HF hospitalizations; and (3) eGFR slope. The direct impact on kidney events was investigated by a prespecified composite kidney outcome (defined as a sustained profound decline in eGFR, chronic dialysis, or transplant). The median follow-up was 16 months.
Of 3730 patients who were randomized to empagliflozin or placebo, 1978 (53%) had CKD. Empagliflozin reduced the primary outcome and total HF hospitalizations in patients with and without CKD: hazard ratio (HR)=0.78 (95% CI, 0.65-0.93) and HR=0.72 (95% CI, 0.58-0.90), respectively (interaction =0.63). Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23-1.98) ml/min/1.73 m/yr in patients with CKD and by 2.41 (1.49-3.32) ml/min/1.73 m/yr in patients without CKD. The risk of the composite kidney outcome was reduced similarly in patients with and without CKD: HR=0.53 (95% CI, 0.31-0.91) and HR=0.46 (95% CI, 0.22-0.99), respectively. The effect of empagliflozin on the primary composite outcome and key secondary outcomes was consistent across a broad range of baseline kidney function, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 ml/min/1.73 m. Empagliflozin was well tolerated in CKD patients.
In EMPEROR-Reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, and regardless of the severity of kidney impairment at baseline. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.
在 EMPEROR-Reduced（慢性心力衰竭射血分数降低患者的恩格列净结局试验）中，恩格列净降低了心血管死亡或心力衰竭（HF）住院和总 HF 住院的发生率，并减缓了射血分数降低的 HF 患者肾功能的进行性下降，无论患者是否患有糖尿病。我们旨在研究恩格列净在整个肾功能范围内对心血管和肾脏结局的影响。
在这项预设分析中，根据基线时是否存在慢性肾脏病（CKD）（估计肾小球滤过率[eGFR] <60 ml/min/1.73 m 或白蛋白/肌酐比值>300 mg/g）对患者进行分类。主要和关键次要结局为：（1）心血管死亡或 HF 住院的复合结局（主要结局）；（2）总 HF 住院；和（3）eGFR 斜率。通过预设的复合肾脏结局（定义为 eGFR 持续显著下降、慢性透析或移植）来研究对肾脏事件的直接影响。中位随访时间为 16 个月。
在被随机分配至恩格列净或安慰剂的 3730 名患者中，有 1978 名（53%）患有 CKD。恩格列净降低了 CKD 患者和无 CKD 患者的主要结局和总 HF 住院发生率：风险比（HR）=0.78（95%CI，0.65-0.93）和 HR=0.72（95%CI，0.58-0.90）（交互作用=0.63）。恩格列净使 CKD 患者的 eGFR 下降斜率减缓了 1.11（0.23-1.98）ml/min/1.73 m/yr，使无 CKD 患者的 eGFR 下降斜率减缓了 2.41（1.49-3.32）ml/min/1.73 m/yr。在 CKD 患者和无 CKD 患者中，复合肾脏结局的风险均相似降低：HR=0.53（95%CI，0.31-0.91）和 HR=0.46（95%CI，0.22-0.99）。恩格列净对主要复合结局和关键次要结局的影响在广泛的基线肾功能范围内是一致的，通过临床相关的 eGFR 亚组或蛋白尿来衡量，包括 eGFR 低至 20 ml/min/1.73 m 的患者。在 CKD 患者中，恩格列净耐受性良好。
在 EMPEROR-Reduced 中，恩格列净对关键疗效结局有有益影响，并减缓了 CKD 患者和无 CKD 患者的肾功能下降速度，无论基线时肾功能损害的严重程度如何。
