ed greater in the most frail participants in this post hoc analysis of EMPA-KIDNEY. Background Sodium-glucose cotransporter-2 inhibitors are recommended treatment for adults with CKD, but uncertainty exists regarding their use in patients with frailty and/or multimorbidity, among whom polypharmacy is common. We derived a multivariable logistic regression model to predict hospitalization (reflecting frailty) and assessed empagliflozin's risk–benefit profile in a post hoc analysis of the double-blind, placebo-controlled EMPA-KIDNEY trial. Methods The EMPA-KIDNEY trial randomized 6609 patients with CKD (eGFR ≥20 to <45 ml/min per 1.73 m2, or ≥45 to <90 ml/min per 1.73 m2 with urinary albumin-to-creatinine ratio ≥200 mg/g) to receive either empagliflozin 10 mg daily or matching placebo and followed them for 2 years (median). Additional characteristics analyzed in subgroups were multimorbidity, polypharmacy, and health-related quality of life at baseline. Cox regression analyses were performed with subgroups defined by approximate thirds of each variable. Results The strongest predictors of hospitalization were N-terminal prohormone of brain natriuretic peptide, poor mobility, and diabetes and then eGFR and other comorbidities. Empagliflozin was generally well tolerated independent of predicted risk of hospitalization. In relative terms, allocation to empagliflozin reduced the risk of the primary outcome of kidney disease progression or cardiovascular death by 28% (hazard ratio, 0.72; 95% confidence interval, 0.64 to 0.82) and all-cause hospitalization by 14% (hazard ratio, 0.86; 95% confidence interval, 0.78 to 0.95), with broadly consistent effects across subgroups of predicted risk of hospitalization, multimorbidity, polypharmacy, or health-related quality of life. In absolute terms, the estimated benefits of empagliflozin were greater in those at highest predicted risk of hospitalization (reflecting frailty) and outweighed potential serious harms. Conclusions These findings support the use of sodium-glucose cotransporter-2 inhibitors in CKD, irrespective of frailty, multimorbidity, or polypharmacy. Clinical Trial registration number: NCT03594110....

中文翻译：

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虚弱、多病共存和多药治疗：EMPA-KIDNEY 试验中 Empagliflozin 效果的探索性分析


在这项 EMPA-KIDNEY 的事后分析中最虚弱的参与者中 ed 更大。背景 钠-葡萄糖协同转运蛋白-2 抑制剂是 CKD 成人患者的推荐治疗方法，但其在虚弱和/或多病共存患者中的使用存在不确定性，其中多药治疗很常见。我们推导出了一个多变量 logistic 回归模型来预测住院 （反映虚弱），并在双盲、安慰剂对照 EMPA-KIDNEY 试验的事后分析中评估了 empagliflozin 的风险-获益概况。方法 EMPA-KIDNEY 试验将 6609 例 CKD 患者（eGFR ≥20 至 <45 ml/min 每 1.73 m2，或 ≥45 至 <90 ml/min 每 1.73 m2，尿白蛋白与肌酐比值 ≥200 mg/g）随机分配至恩格列净 10 mg /d或匹配的安慰剂组，并随访 2 年（中位数）。亚组分析的其他特征是共存、多药治疗和基线时与健康相关的生活质量。对由每个变量的大约三分之一定义的子组进行 Cox 回归分析。结果 住院的最强预测因素是脑利钠肽 N 末端激素原、活动能力差、糖尿病，然后是 eGFR 和其他合并症。恩格列净通常耐受性良好，与预测的住院风险无关。相对而言，恩格列净组将肾病进展或心血管死亡的主要结局风险降低了 28%（风险比，0.72;95% 置信区间，0.64 至 0.82），全因住院风险降低了 14%（风险比，0.86;95% 置信区间，0.78 至 0.95），预测住院风险的亚组影响大致一致， 多病共存、多药治疗或与健康相关的生活质量。 从绝对值来看，恩格列净在预测住院风险最高 （反映虚弱） 的患者中估计的益处更大，并且超过了潜在的严重危害。结论 这些发现支持在 CKD 中使用钠-葡萄糖协同转运蛋白 2 抑制剂，无论虚弱、多病共存或多药治疗。临床试验注册号：NCT03594110....