Department of Medicine, University of Michigan School of Medicine, Ann Arbor.
Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis.
JAMA Netw Open. 2022 Oct 3;5(10):e2236123. doi: 10.1001/jamanetworkopen.2022.36123.
IMPORTANCE: Patients with chronic kidney disease and type 2 diabetes have a higher risk of developing pneumonia as well as an increased risk of severe COVID-19-associated adverse events and mortality. Therefore, the anti-inflammatory effects of mineralocorticoid receptor antagonists via blockade of the mineralocorticoid receptor may alter the risk of pneumonia and COVID-19-associated adverse events in patients with chronic kidney disease and type 2 diabetes. OBJECTIVE: To evaluate whether the selective, nonsteroidal mineralocorticoid receptor antagonist finerenone is associated with protection against pneumonia and COVID-19 adverse events in patients with type 2 diabetes and chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis used patient-level data from FIDELITY, a prespecified pooled analysis of 2 multicenter, double-blind, placebo-controlled, event-driven, phase 3 randomized clinical trials: FIDELIO-DKD and FIGARO-DKD, conducted between September 2015 and February 2021. Patients in FIDELIO-DKD or FIGARO-DKD with type 2 diabetes and chronic kidney disease (urine albumin to creatine ratio, 30-5000 mg/g, estimated glomerular filtration rate ≥25 mL/min/1.73 m2) were assessed. Data were analyzed from May 15, 2021, to July 28, 2022. EXPOSURE: Patients were randomized to finerenone (10 or 20 mg once daily) or matching placebo. MAIN OUTCOMES AND MEASURES: The main outcomes were investigator-reported incidences of treatment-emergent infective pneumonia adverse events and serious adverse events (during and up to 3 days after treatment) and any COVID-19 adverse events. RESULTS: Of 13 026 randomized patients (mean [SD] age, 64.8 [9.5] years; 9088 [69.8%] men), 12 999 were included in the FIDELITY safety population (6510 patients receiving finerenone; 6489 patients receiving placebo). Over a median (range) treatment duration of 2.6 (0-5.1) years, finerenone was consistently associated with reduced risk of pneumonia and serious pneumonia vs placebo. Overall, 307 patients (4.7%) treated with finerenone and 434 patients (6.7%) treated with placebo experienced pneumonia (hazard ratio [HR], 0.71; 95% CI, 0.64-0.79; P < .001). Serious pneumonia occurred in 171 patients (2.6%) treated with finerenone and 250 patients (3.9%) treated with placebo (HR, 0.69; 95% CI, 0.60-0.79; P < .001). Incidence proportions of COVID-19 adverse events were 86 patients (1.3%) in the finerenone group and 118 patients (1.8%) in the placebo group (HR, 0.73; 95% CI, 0.60-0.89; P = .002). CONCLUSIONS AND RELEVANCE: These findings suggest that mineralocorticoid receptor blockade with finerenone was associated with protection against pneumonia and COVID-19 adverse events in patients with type 2 diabetes and chronic kidney disease. Further clinical studies may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: FIDELIO-DKD: NCT02540993; FIGARO-DKD: NCT02545049.
重要性:患有慢性肾脏病和 2 型糖尿病的患者发生肺炎以及 COVID-19 相关不良事件和死亡率增加的风险更高。因此,通过阻断盐皮质激素受体,盐皮质激素受体拮抗剂的抗炎作用可能会改变慢性肾脏病和 2 型糖尿病患者发生肺炎和 COVID-19 相关不良事件的风险。 目的:评估选择性非甾体类盐皮质激素受体拮抗剂非奈利酮是否与预防 2 型糖尿病和慢性肾脏病患者的肺炎和 COVID-19 不良事件相关。 设计、设置和参与者:这是一项二次分析,使用了 FIDELITY 研究的患者水平数据,这是两项多中心、双盲、安慰剂对照、事件驱动、3 期随机临床试验的预设汇总分析:FIDELIO-DKD 和 FIGARO-DKD,研究时间分别为 2015 年 9 月至 2021 年 2 月。评估了 FIDELIO-DKD 或 FIGARO-DKD 中患有 2 型糖尿病和慢性肾脏病(尿白蛋白与肌酐比,30-5000mg/g,估计肾小球滤过率≥25ml/min/1.73m2)的患者。数据分析于 2021 年 5 月 15 日至 2022 年 7 月 28 日进行。 暴露:患者被随机分配接受非奈利酮(10 或 20mg,每日一次)或匹配的安慰剂。 主要结局和测量:主要结局是研究者报告的治疗出现的感染性肺炎不良事件和严重不良事件(治疗期间和治疗后 3 天内)的发生率以及任何 COVID-19 不良事件。 结果:在 13026 名随机患者中(平均[标准差]年龄,64.8[9.5]岁;9088[69.8%]名男性),12999 名患者纳入了 FIDELITY 安全性人群(6510 名接受非奈利酮治疗的患者;6489 名接受安慰剂治疗的患者)。在中位数(范围)为 2.6(0-5.1)年的治疗期间,非奈利酮与降低肺炎和严重肺炎的风险与安慰剂一致。总体而言,307 名(4.7%)接受非奈利酮治疗的患者和 434 名(6.7%)接受安慰剂治疗的患者发生肺炎(风险比[HR],0.71;95%置信区间,0.64-0.79;P<0.001)。171 名(2.6%)接受非奈利酮治疗的患者和 250 名(3.9%)接受安慰剂治疗的患者发生严重肺炎(HR,0.69;95%置信区间,0.60-0.79;P<0.001)。COVID-19 不良事件的发生率比例在非奈利酮组为 86 名(1.3%)患者,在安慰剂组为 118 名(1.8%)患者(HR,0.73;95%置信区间,0.60-0.89;P=0.002)。 结论和相关性:这些发现表明,非奈利酮阻断盐皮质激素受体与 2 型糖尿病和慢性肾脏病患者的肺炎和 COVID-19 不良事件的预防有关。可能需要进一步的临床研究。 试验注册:ClinicalTrials.gov 标识符:FIDELIO-DKD:NCT02540993;FIGARO-DKD:NCT02545049。
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