Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function: Insights From EMPEROR-Reduced.
Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function: Insights From EMPEROR-Reduced.
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DOI：
10.1161/circulationaha.120.051685
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发表时间：
2021-01-26
期刊：
影响因子：
37.8
通讯作者：
Packer M
中科院分区：
文献类型：
--
作者：
Zannad F;Ferreira JP;Pocock SJ;Zeller C;Anker SD;Butler J;Filippatos G;Hauske SJ;Brueckmann M;Pfarr E;Schnee J;Wanner C;Packer M
补充数字内容可在文本中找到。在EMPEROR-Reduced（恩格列净在慢性心力衰竭伴射血分数降低患者中的结局试验）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，并减缓了伴有和不伴有糖尿病的HF伴射血分数降低患者肾功能的进行性下降。我们的目的是研究恩格列净对心血管和肾脏功能的影响。在这个预先指定的分析中，患者在基线时（估计肾小球滤过率[eGFR] <60 ml/min/1.73 m2或白蛋白与肌酸比>300 mg/g）根据是否存在慢性肾脏疾病（CKD）进行分类。主要结局和关键次要结局为：(1)心血管死亡或心衰住院的复合结局（主要结局）；(2) HF住院总人数；(3) eGFR斜率。通过预先指定的复合肾脏结局（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3730名随机接受恩格列净或安慰剂治疗的患者中，1978名（53%）患有CKD。恩帕列净降低了有和无CKD患者的主要结局和HF总住院率：风险比（HR）分别=0.78 （95% CI, 0.65-0.93）和HR=0.72 (95% CI, 0.58-0.90)（相互作用P=0.63）。恩帕列净减缓慢性肾病患者eGFR下降的斜率为1.11 (0.23-1.98)ml/min/1.73 m2/yr，非慢性肾病患者为2.41 (1.49-3.32)ml/min/1.73 m2/yr。合并和不合并CKD的患者发生复合肾脏结局的风险同样降低：HR分别=0.53 （95% CI, 0.31-0.91）和HR=0.46 （95% CI, 0.22-0.99）。依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亚组或蛋白尿来测量，包括eGFR低至20 ml/min/1.73 m2的患者。恩帕列净在CKD患者中耐受性良好。在EMPEROR-Reduced中，恩格列净对关键疗效结果有有益影响，减缓了有或无CKD患者肾功能下降的速度，无论基线时肾脏损害的严重程度如何。URL: https://www.clinicaltrials.gov;唯一标识符：NCT03057977。
Supplemental Digital Content is available in the text. 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 m2 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 P=0.63). Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23–1.98) ml/min/1.73 m2/yr in patients with CKD and by 2.41 (1.49–3.32) ml/min/1.73 m2/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 m2. 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. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.