A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease.
A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease.
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DOI：
10.1093/eurheartj/ehw132
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发表时间：
2016-07-14
影响因子：
39.3
通讯作者：
Pitt B
中科院分区：
文献类型：
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作者：
Filippatos G;Anker SD;Böhm M;Gheorghiade M;Køber L;Krum H;Maggioni AP;Ponikowski P;Voors AA;Zannad F;Kim SY;Nowack C;Palombo G;Kolkhof P;Kimmeskamp-Kirschbaum N;Pieper A;Pitt B
评价心力衰竭加重、射血分数降低、慢性肾病和/或糖尿病患者口服非甾体矿皮质激素受体拮抗剂芬那酮90天的剂量。Miner al皮质激素受体拮抗剂耐受性研究-心力衰竭（ARTS-HF）是一项随机、双盲、2b期多中心研究（ClinicalTrials.gov: NCT01807221）。在1286名筛选的患者中，1066名被随机分组。患者接受口服，每天一次的芬尼酮（2.5、5、7.5、10或15毫克，分别在第30天增加到5、10、15、20或20毫克）或依普利酮（每隔一天25毫克，在第30天增加到每天25毫克，在第60天增加到每天50毫克），持续90天。主要终点是从基线到第90天血浆n端前b型利钠肽（NT-proBNP）下降bbb30 %的个体百分比。一个关键的探索性终点是一个复合临床终点，即任何原因导致的死亡、心血管住院或90天前因心衰恶化而出现的紧急症状。不同治疗组的平均年龄为69.2 ~ 72.5岁（标准差9.7 ~ 10.6岁）。依普利酮组37.2%的患者NT-proBNP较基线下降了30%，2.5→5、5→10、7.5→15、10→20和15→20 mg的患者NT-proBNP分别下降了30.9%、32.5、37.3%、38.8%和34.2% （P = 0.42-0.88）。除2.5 ~ 5mg芬尼酮组外，与依普利酮组相比，芬尼酮组复合临床终点的发生率较低；该差异在10→20 mg组达到了名义上的统计学意义（风险比0.56,95%可信区间CI， 0.35; 0.90；名义P = 0.02），尽管本2期研究的设计并不是为了检测统计学上的显著差异。4.3%的患者在任何时间点钾水平升高至≥5.6 mmol/L，在所有治疗组中分布均衡。芬尼酮耐受性良好，与依普利酮相似比例的患者NT-proBNP水平下降30%或更多。芬烯酮10→20 mg组的临床事件减少的发现应在大型结局试验中进一步探讨。
To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7–10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42–0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced distribution among all treatment groups. Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial.