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、多重疾病和多重用药：EMPA-KIDNEY 试验中恩格列净效果的探索性分析


在 EMPA-KIDNEY 的事后分析中，最虚弱的参与者的情况更明显。背景 钠-葡萄糖协同转运蛋白 2 抑制剂是成人 CKD 的推荐治疗方法，但其在虚弱和/或多病患者中的使用存在不确定性，其中多药治疗很常见。我们推导了一个多变量逻辑回归模型来预测住院治疗（反映虚弱程度），并在双盲、安慰剂对照 EMPA-KIDNEY 试验的事后分析中评估了恩格列净的风险-效益概况。方法 EMPA-KIDNEY 试验将 6609 名 CKD 患者随机分组（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 ）每天接受恩格列净 10 毫克或匹配的安慰剂，并随访 2 年（中位数）。亚组中分析的其他特征包括基线时的多重发病、多重用药和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亚组进行 Cox 回归分析。结果 住院的最强预测因素是脑钠肽 N 末端激素原、活动能力差和糖尿病，然后是 eGFR 和其他合并症。恩格列净通常耐受性良好，与预计的住院风险无关。相对而言，分配至恩格列净可将肾脏疾病进展或心血管死亡的主要结局风险降低 28%（风险比，0.72；95% 置信区间，0.64 至 0.82），将全因住院风险降低 14%（风险比） ，0.86；95% 置信区间，0.78 至 0.95），对住院、多病、多药治疗或健康相关生活质量的预测风险的亚组具有大致一致的影响。 从绝对值来看，对于那些预计住院风险最高（反映虚弱）的人来说，恩格列净的估计益处更大，并且超过了潜在的严重危害。结论 这些发现支持钠-葡萄糖协同转运蛋白 2 抑制剂在 CKD 中的使用，无论是否虚弱、多种疾病或多药治疗。临床试验注册号：NCT03594110....