Frailty, multimorbidity and polypharmacy: exploratory analyses of the effects of empagliflozin from the EMPA-KIDNEY trial.

IF 8.5 1区医学 Q1 UROLOGY & NEPHROLOGY

Clinical Journal of the American Society of Nephrology Pub Date : 2024-07-01 DOI:10.2215/CJN.0000000000000498

Kaitlin J Mayne, Rebecca J Sardell, Natalie Staplin, Parminder K Judge, Doreen Zhu, Emily Sammons, David Zi Cherney, Alfred K Cheung, Aldo P Maggioni, Masaomi Nangaku, Xavier Rossello, Katherine R Tuttle, Katsuhito Ihara, Tomoko Iwata, Christoph Wanner, Jonathan Emberson, David Preiss, Martin J Landray, Colin Baigent FMedSci, Richard Haynes, William G Herrington

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引用次数: 0

Abstract

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recommended treatment for adults with chronic kidney disease (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 (estimated glomerular filtration rate [eGFR] ≥20<45 mL/min/1.73m2, or ≥45<90 mL/min/1.73m2 with urinary albumin-to-creatinine ratio ≥200 mg/g) to receive either empagliflozin 10 mg daily or matching placebo and followed for two years (median). Additional characteristics analysed in subgroups were multimorbidity, polypharmacy and health-related quality of life (HRQoL) 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; 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 [HR] 0.72, 95% confidence interval [CI] 0.64-0.82); and all-cause hospitalization by 14% (HR 0.86, 95% CI 0.78-0.95); with broadly consistent effects across subgroups of predicted risk of hospitalization, multimorbidity, polypharmacy or HRQoL. 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 SGLT2 inhibitors in CKD, irrespective of frailty, multimorbidity or polypharmacy.

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虚弱、多病和多重用药：EMPA-KIDNEY 试验中对安格列酮影响的探索性分析。

背景：钠-葡萄糖共转运体-2（SGLT2）抑制剂是慢性肾脏病（CKD）成人患者的推荐治疗药物，但在体弱和/或多病的患者中使用该药物还存在不确定性，因为在这些患者中使用多种药物很常见。我们在双盲安慰剂对照 EMPA-KIDNEY 试验的事后分析中得出了一个预测住院（反映虚弱）的多变量逻辑回归模型，并评估了恩格列净的风险-获益情况：EMPA-KIDNEY试验随机抽取了6609名CKD患者（估计肾小球滤过率[eGFR]≥20）：最能预测住院的因素是脑钠肽N末端前体、行动不便和糖尿病，然后是肾小球滤过率和其他合并症。恩格列净的耐受性普遍良好，与预测的住院风险无关。相对而言，接受恩格列净治疗后，肾病进展或心血管死亡的主要结局风险降低了28%（危险比[HR]0.72，95%置信区间[CI]0.64-0.82）；全因住院风险降低了14%（HR 0.86，95%置信区间[CI]0.78-0.95）；在预测住院风险、多病症、多重用药或HRQoL的亚组中，效果基本一致。从绝对值来看，empagliflozin对预测住院风险最高者（反映了虚弱程度）的估计益处更大，超过了潜在的严重危害：这些研究结果支持在慢性肾脏病患者中使用 SGLT2 抑制剂，无论患者是否体弱、多病或多药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Journal of the American Society of Nephrology 医学-泌尿学与肾脏学

CiteScore

12.20

自引率

3.10%

发文量

514

审稿时长

3-6 weeks

期刊介绍： The Clinical Journal of the American Society of Nephrology strives to establish itself as the foremost authority in communicating and influencing advances in clinical nephrology by (1) swiftly and effectively disseminating pivotal developments in clinical and translational research in nephrology, encompassing innovations in research methods and care delivery; (2) providing context for these advances in relation to future research directions and patient care; and (3) becoming a key voice on issues with potential implications for the clinical practice of nephrology, particularly within the United States. Original manuscript topics cover a range of areas, including Acid/Base and Electrolyte Disorders, Acute Kidney Injury and ICU Nephrology, Chronic Kidney Disease, Clinical Nephrology, Cystic Kidney Disease, Diabetes and the Kidney, Genetics, Geriatric and Palliative Nephrology, Glomerular and Tubulointerstitial Diseases, Hypertension, Maintenance Dialysis, Mineral Metabolism, Nephrolithiasis, and Transplantation.