Wada Takashi, Anker Stefan D, Liu Zhihong, Lee Byung Wan, Lee Chien-Te, Rossing Peter, Ruilope Luis M, Ahlers Christiane, Brinker Meike, Mann Amaninder, Yamashita Satoshi, Pitt Bertram
Department of Nephrology and Rheumatology, Kanazawa University, Kanazawa, Japan.
Department of Cardiology (CVK) of German Heart Center Charité, German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.
Kidney Dis (Basel). 2025 May 22;11(1):402-415. doi: 10.1159/000545415. eCollection 2025 Jan-Dec.
INTRODUCTION: In FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone reduced the risk of cardiovascular (CV) and kidney events versus placebo in patients with type 2 diabetes and chronic kidney disease, on optimized renin-angiotensin system blockade. This FIDELITY post hoc subanalysis explores the efficacy and safety of finerenone in Asian patients. METHODS: For this subanalysis, efficacy outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decrease from baseline over ≥4 weeks or renal death) outcome. A change in urine albumin-to-creatinine ratio (UACR) from baseline to month 4 and eGFR slopes was also assessed. All outcomes were assessed by baseline eGFR (<60 and ≥60 mL/min/1.73 m) and UACR (<300 and ≥300 mg/g) subgroups. Safety outcomes were reported as treatment-emergent adverse events, including laboratory evaluations for hyperkalemia. RESULTS: In the Asian subpopulation, 1,412/2,858 (49.4%) received finerenone. Finerenone-treated Asian patients had a lower risk of the composite CV outcome (hazard ratio [HR] = 0.90; 95% confidence interval [CI], 0.70-1.15) and nominally significant reductions in the risk of ≥57% and ≥40% eGFR composite kidney outcomes (HR = 0.64; 95% CI, 0.50-0.82 and HR = 0.67; 95% CI, 0.56-0.80, respectively) versus those receiving placebo, irrespective of baseline eGFR and UACR. Data on change of eGFR from baseline over the course of the trials indicated that chronic kidney disease progression in Asian patients was slower with finerenone versus placebo. Overall, safety outcomes were balanced between both populations. Serum potassium values with finerenone were similar between the Asian and non-Asian subpopulations (>5.5 mmol/L: 15.6% versus 17.1%; >6.0 mmol/L: 4.6% versus 2.9%, respectively), while hyperkalemia leading to permanent treatment discontinuation with finerenone was low in both populations (Asian: 1.5%; non-Asian: 1.8%). CONCLUSION: Finerenone reduced the risk of CV and kidney events and demonstrated a well-tolerated safety profile in the FIDELITY Asian subpopulation.
简介:在FIDELITY研究中,对III期FIDELIO-DKD和FIGARO-DKD试验进行了预先指定的汇总分析,在接受优化肾素-血管紧张素系统阻断治疗的2型糖尿病和慢性肾脏病患者中,非奈利酮相较于安慰剂降低了心血管(CV)和肾脏事件风险。这项FIDELITY事后亚组分析探讨了非奈利酮在亚洲患者中的疗效和安全性。 方法:对于该亚组分析,疗效结局包括CV复合结局(CV死亡、非致死性心肌梗死、非致死性中风或因心力衰竭住院的时间)和肾脏复合结局(肾衰竭、估计肾小球滤过率[eGFR]自基线持续下降≥57%超过≥4周或肾脏死亡)。还评估了从基线到第4个月尿白蛋白与肌酐比值(UACR)的变化以及eGFR斜率。所有结局均按基线eGFR(<60和≥60 mL/min/1.73 m²)和UACR(<300和≥300 mg/g)亚组进行评估。安全性结局报告为治疗期间出现的不良事件,包括高钾血症的实验室评估。 结果:在亚洲亚组中,1412/2858(49.4%)的患者接受了非奈利酮治疗。接受非奈利酮治疗的亚洲患者发生复合CV结局的风险较低(风险比[HR]=0.90;95%置信区间[CI],0.70-1.15),≥57%和≥40% eGFR复合肾脏结局的风险名义上有显著降低(HR分别为0.64;95% CI,0.50-0.82和HR=0.67;95% CI,0.56-0.80),与接受安慰剂的患者相比,无论基线eGFR和UACR如何。试验过程中eGFR自基线变化的数据表明,与安慰剂相比,亚洲患者中使用非奈利酮时慢性肾脏病进展较慢。总体而言,两个亚组的安全性结局相当。亚洲和非亚洲亚组中使用非奈利酮时的血清钾值相似(>5.5 mmol/L:分别为15.6%和17.1%;>6.0 mmol/L:分别为4.6%和2.9%),而因高钾血症导致非奈利酮治疗永久停药的情况在两个亚组中均较低(亚洲:1.5%;非亚洲:1.8%)。 结论:在FIDELITY亚洲亚组中,非奈利酮降低了CV和肾脏事件风险,并显示出耐受性良好的安全性。
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