Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes
Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes
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DOI：
10.1056/nejmoa2110956
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发表时间：
2021-08-28
影响因子：
158.5
通讯作者：
Ruilope, Luis M.
中科院分区：
文献类型：
--
作者：
Pitt, Bertram;Filippatos, Gerasimos;Ruilope, Luis M.
芬纳烯酮是一种选择性非甾体类矿物皮质激素受体拮抗剂，对伴有严重蛋白尿和2型糖尿病的3期或4期慢性肾病（CKD）患者的心肾预后有良好的影响。芬烯酮在2型糖尿病和更广泛的CKD患者中的应用尚不清楚。方法在这项双盲试验中，我们随机分配CKD和2型糖尿病患者接受芬尼酮或安慰剂治疗。符合条件的患者尿白蛋白与肌酐比值（白蛋白以毫克为单位测量，肌酐以克为单位测量）为30 -小于300，估计肾小球滤过率（eGFR）为每1.73 m(2)体表面积25 - 90ml /分钟（2 - 4期CKD）或尿白蛋白与肌酐比值为300 - 5000，eGFR至少为每1.73 m(2) 60 ml /分钟（1期或2期CKD）。患者接受肾素-血管紧张素系统阻滞剂治疗，在随机分组之前已调整到制造商标签上没有引起不可接受的副作用的最大剂量。在事件时间分析中评估的主要结局是心血管原因死亡、非致死性心肌梗死、非致死性中风或因心力衰竭住院。第一个次要结局是肾功能衰竭，eGFR从基线持续下降至少40%，或肾脏原因死亡。安全性评估为研究者报告的不良事件。结果共7437例患者进行了随机分组。在纳入分析的患者中，在3.4年的中位随访期间，芬尼酮组3686例患者中有458例（12.4%）发生了主要结局事件，安慰剂组3666例患者中有519例（14.2%）发生了主要结局事件（风险比为0.87；95%可信区间[CI]， 0.76至0.98;P = 0.03），主要受益于心力衰竭住院发生率较低（风险比为0.71;95% CI， 0.56至0.90）。芬尼酮组有350例（9.5%）患者出现二次复合结局，安慰剂组有395例（10.8%）患者出现二次复合结局（风险比，0.87;95% CI, 0.76 ~ 1.01）。不良事件的总体频率在两组之间没有显著差异。芬尼酮组因高钾血症而中断试验方案的发生率（1.2%）高于安慰剂组（0.4%）。结论：在2型糖尿病和2 - 4期CKD伴蛋白尿中度升高或1 - 2期CKD伴蛋白尿严重升高的患者中，与安慰剂相比，芬尼酮治疗改善了心血管预后。
BACKGROUNDFinerenone, 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.METHODSIn 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-tocreatinine 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 m(2) 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 m(2) (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.RESULTSA 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%).CONCLUSIONSAmong 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.