衰弱、多病共存与多重用药：来自恩格列净治疗慢性肾脏病（EMPA-KIDNEY）试验的探索性分析
Frailty, Multimorbidity, and Polypharmacy: Exploratory Analyses of the Effects of Empagliflozin from the EMPA-KIDNEY Trial.
作者信息
Mayne Kaitlin J, Sardell Rebecca J, Staplin Natalie, Judge Parminder K, Zhu Doreen, Sammons Emily, Cherney David Z I, Cheung Alfred K, Maggioni Aldo P, Nangaku Masaomi, Rossello Xavier, Tuttle Katherine R, Ihara Katsuhito, Iwata Tomoko, Wanner Christoph, Emberson Jonathan, Preiss David, Landray Martin J, Baigent Colin, Haynes Richard, Herrington William G
机构信息
Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
School of Cardiovascular and Metabolic Health, College of Medical and Veterinary Life Sciences, University of Glasgow, Glasgow, United Kingdom.
出版信息
Clin J Am Soc Nephrol. 2024 Sep 1;19(9):1119-1129. doi: 10.2215/CJN.0000000000000498. Epub 2024 Jun 27.
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.
背景
钠-葡萄糖协同转运蛋白2抑制剂被推荐用于治疗成年慢性肾脏病患者，但对于其在虚弱和/或多病共存患者中的应用仍存在不确定性，这类患者通常使用多种药物。我们推导了一个多变量逻辑回归模型来预测住院情况（反映虚弱程度），并在双盲、安慰剂对照的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例慢性肾脏病患者（估算肾小球滤过率≥20至<45 ml/min/1.73 m²，或≥45至<90 ml/min/1.73 m²且尿白蛋白与肌酐比值≥200 mg/g）随机分为两组，分别接受每日10 mg恩格列净或匹配的安慰剂治疗，并随访2年（中位数）。在亚组中分析的其他特征包括多病共存、多种药物治疗以及基线时与健康相关的生活质量。使用每个变量大致三等分定义的亚组进行Cox回归分析。
结果
住院的最强预测因素是脑钠肽前体N端、行动不便和糖尿病，其次是估算肾小球滤过率和其他合并症。无论预测的住院风险如何，恩格列净总体耐受性良好。相对而言，分配到恩格列净组可使肾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），全因住院风险降低14%（风险比，0.86；95%置信区间，0.78至0.95），在预测住院风险、多病共存、多种药物治疗或与健康相关的生活质量的亚组中效果大致一致。从绝对数值来看，恩格列净在预测住院风险最高（反映虚弱）的患者中的估计益处更大，且超过了潜在的严重危害。
结论
这些发现支持在慢性肾脏病患者中使用钠-葡萄糖协同转运蛋白2抑制剂，无论其是否虚弱、多病共存或使用多种药物。
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