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肾脏疾病和2型糖尿病患者服用finerenone可显著降低心血管风险
作者:小柯机器人 发布时间:2021/8/31 14:26:32

美国密歇根大学医学院Bertram Pitt团队研究了肾脏疾病和2型糖尿病患者服用finerenone后的心血管事件。相关论文发表在2021年8月27日出版的《新英格兰医学杂志》上。

Finerenone是一种选择性非甾体盐皮质激素受体拮抗剂,对主要为3或4期慢性肾病(CKD)、蛋白尿严重升高和2型糖尿病患者的心肾结局有良好效果。但Finerenone在2型糖尿病和更广泛的CKD患者中的应用尚不清楚。

在这项双盲试验中,研究组招募CKD和2型糖尿病患者,将其随机分配接受finerenone或安慰剂治疗。符合条件的患者的尿白蛋白与肌酐的比率(白蛋白以mg计,肌酐以g计)为30到300,估计肾小球滤过率(eGFR)为25到90 mL/min/1.73m2体表面积(2到4期 CKD),或尿白蛋白与肌酐的比率为300到5000,以及eGFR至少为60 mL/min/1.73m2(1或2期CKD)。

患者接受肾素-血管紧张素系统阻断剂治疗,在随机化前已调整至制造商标签上的最大剂量,未造成不可接受的副作用。在事件-时间分析中评估的主要结局是心血管原因死亡、非致命性心肌梗死、非致命性中风或因心力衰竭住院。关键次要结局是肾功能衰竭、eGFR从基线水平持续下降至少40%或因肾原因死亡。安全性评估为研究者报告的不良事件。

共有7437名患者接受了随机分组。在纳入分析的患者中,在3.4年的中位随访期间,finerenone组3686名患者中有458名(12.4%)发生主要结局事件,安慰剂组3666名患者中有519名(14.2%),危险比为0.87,主要是由于心力衰竭住院率较低,风险比为0.71。

Finerenone组有350名患者(9.5%)发生关键次要结局,安慰剂组有395名(10.8%),风险比为0.87。两组之间不良事件的总体发生率没有显著差异。Finerenone组(1.2%)与安慰剂组(0.4%)相比,试验方案中与高钾血症相关的停药发生率更高。

研究结果表明,对于2型糖尿病和2-4期CKD伴中度蛋白尿升高或1-2期CKD伴严重蛋白尿升高的患者,采用finerenone治疗,与安慰剂相比显著改善了心血管结局。

附:英文原文

Title: Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes | NEJM

Author: Bertram Pitt, M.D.,, Gerasimos Filippatos, M.D.,, Rajiv Agarwal, M.D.,, Stefan D. Anker, M.D., Ph.D.,, George L. Bakris, M.D.,, Peter Rossing, M.D.,, Amer Joseph, M.B., B.S.,, Peter Kolkhof, Ph.D.,, Christina Nowack, M.D.,, Patrick Schloemer, Ph.D.,, and Luis M. Ruilope, M.D.

Issue&Volume: 2021-08-27

Abstract:

Background

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has favorable effects on cardiorenal outcomes in patients with predominantly stage 3 or 4 chronic kidney disease (CKD) with severely elevated albuminuria and type 2 diabetes. The use of finerenone in patients with type 2 diabetes and a wider range of CKD is unclear.

Methods

In this double-blind trial, we randomly assigned patients with CKD and type 2 diabetes to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300 and an estimated glomerular filtration rate (eGFR) of 25 to 90 ml per minute per 1.73 m2 of body-surface area (stage 2 to 4 CKD) or a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of at least 60 ml per minute per 1.73 m2 (stage 1 or 2 CKD). Patients were treated with renin–angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer’s label that did not cause unacceptable side effects. The primary outcome, assessed in a time-to-event analysis, was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The first secondary outcome was a composite of kidney failure, a sustained decrease from baseline of at least 40% in the eGFR, or death from renal causes. Safety was assessed as investigator-reported adverse events.

Results

A total of 7437 patients underwent randomization. Among the patients included in the analysis, during a median follow-up of 3.4 years, a primary outcome event occurred in 458 of 3686 patients (12.4%) in the finerenone group and in 519 of 3666 (14.2%) in the placebo group (hazard ratio, 0.87; 95% confidence interval [CI], 0.76 to 0.98; P=0.03), with the benefit driven primarily by a lower incidence of hospitalization for heart failure (hazard ratio, 0.71; 95% CI, 0.56 to 0.90). The secondary composite outcome occurred in 350 patients (9.5%) in the finerenone group and in 395 (10.8%) in the placebo group (hazard ratio, 0.87; 95% CI, 0.76 to 1.01). The overall frequency of adverse events did not differ substantially between groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone (1.2%) than with placebo (0.4%).

Conclusions

Among patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria, finerenone therapy improved cardiovascular outcomes as compared with placebo.

DOI: 10.1056/NEJMoa2110956

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2110956

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home