National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Attikon University Hospital, Athens, Greece.
Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA.
J Am Coll Cardiol. 2021 Jul 13;78(2):142-152. doi: 10.1016/j.jacc.2021.04.079. Epub 2021 May 17.
Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models.
This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study.
Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF.
Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively).
In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993).
患有慢性肾脏病（CKD）和 2 型糖尿病（T2D）的患者由于心脏重构和肾脏并发症而面临心房颤动或扑动（AFF）的风险。非奈利酮是一种新型、选择性、非甾体类盐皮质激素受体拮抗剂，在临床前模型中抑制了心脏重构。
本研究旨在通过 FIDELIO-DKD 研究中既往有 AFF 病史的患者，评估非奈利酮对新发 AFF 及心脏肾脏的影响。
将患有 CKD 和 T2D 的患者随机（1:1）分为非奈利酮或安慰剂组。合格患者的尿白蛋白与肌酐比值≥30 至≤5000mg/g，估算肾小球滤过率（eGFR）≥25 至<75ml/min/1.73m，并接受优化剂量的肾素-血管紧张素系统阻断剂治疗。新发 AFF 作为独立心脏病专家委员会判定的预先指定的结局进行评估。主要复合结局（首次发生肾衰竭、eGFR 从基线持续下降≥40%或因肾脏原因死亡）和关键次要结局（首次发生心血管死亡、非致死性心肌梗死、非致死性卒中和因心力衰竭住院）按既往 AFF 病史进行分析。
在 5674 名患者中，461 名（8.1%）有 AFF 病史。非奈利酮组 82 名（3.2%）和安慰剂组 117 名（4.5%）患者发生新发 AFF（风险比：0.71；95%置信区间：0.53-0.94；p=0.016）。既往 AFF 对非奈利酮治疗肾脏和心血管主要及关键次要结局的影响无显著差异（交互 p 值分别为 0.16 和 0.85）。
在患有 CKD 和 T2D 的患者中，非奈利酮降低了新发 AFF 的风险。无论基线时是否有 AFF 病史，均可降低肾脏或心血管事件的风险。（EudraCT 2015-000990-11[一项随机、双盲、安慰剂对照、平行组、多中心、事件驱动的 III 期研究，旨在评估非奈利酮在标准治疗的基础上，对 2 型糖尿病和临床诊断为糖尿病肾病的患者的肾脏疾病进展的疗效和安全性]；非奈利酮在 2 型糖尿病和糖尿病肾病患者中的疗效和安全性[FIDELIO-DKD]；NCT02540993）。
