Pérez Martínez Bryan O, Adie Sarah K, Marshall Vincent D, Konerman Matthew C
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Clinical Pharmacy, University of Michigan, Ann Arbor, MI, USA.
ESC Heart Fail. 2023 Oct;10(5):3223-3226. doi: 10.1002/ehf2.14489. Epub 2023 Aug 7.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease mortality and risk of hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate rates of acute kidney injury (AKI) and therapy discontinuation with SGLT2i initiation in a real-world cohort of HFrEF patients.
We abstracted data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting at the University of Michigan (between 1 July 2016 and 2 July 2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. A total of 200 patients were included. The majority of patients were male (64%) with a mean left ventricular ejection fraction (LVEF) of 27%. One hundred and four (52%) patients had diabetes mellitus. Most patients exhibited New York Heart Association class II (51.5%) or III (33.5%) symptoms. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. AKI occurred in 22 patients and 18 patients discontinued their SGLT2i. Yeast infection (n = 6), hypotension (n = 5), and AKI (n = 4) were the most common reasons for discontinuation. Using receiver operating characteristic curve analysis, the strongest models for AKI were A1C [area underneath its curve (AUC) = 75.8, empirical confidence interval (ECI) 66.5-83.5]; baseline serum creatinine (SCr) (AUC = 72.0, ECI 65.7-78.7); LVEF (AUC = 67.6, ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0, ECI 57.5-74.6). Similarly, the strongest positive models for SGLT2i discontinuation were A1C (AUC = 81.1, ECI 74.8-87.2); baseline SCr (AUC = 67.4, ECI 58.7-75.5); LVEF (AUC = 68.7, ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2, ECI 58.2-76.0).
A1C was the strongest model of AKI, and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. Patients with higher baseline SCr on higher doses of loop diuretics may be at greater risk of these outcomes. Future prospective studies will be needed to further evaluate these findings and other models of AKI and SGLT2i discontinuation to guide clinical use of SGLT2 inhibitors.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可降低射血分数降低的心力衰竭（HFrEF）患者的死亡率和住院风险。SGLT2i在开始使用后不久具有利钠作用，随后是持久的渗透性利尿作用。我们试图评估在HFrEF患者的真实世界队列中开始使用SGLT2i后的急性肾损伤（AKI）发生率和治疗中断情况。
我们提取了密歇根大学门诊开始使用SGLT2i的200例HFrEF患者的数据（2016年7月1日至2022年7月2日）。我们的共同主要终点是AKI发生率和SGLT2i停药情况。共纳入200例患者。大多数患者为男性（64%），平均左心室射血分数（LVEF）为27%。104例（52%）患者患有糖尿病。大多数患者表现为纽约心脏协会II级（51.5%）或III级（33.5%）症状。大多数患者（54%）正在服用血管紧张素受体脑啡肽酶抑制剂。平均每日呋塞米等效利尿剂量为93.3毫克。22例患者发生AKI，18例患者停用SGLT2i。酵母菌感染（n = 6）、低血压（n = 5）和AKI（n = 4）是停药的最常见原因。使用受试者工作特征曲线分析，AKI的最强预测模型是糖化血红蛋白A1C [其曲线下面积（AUC）= 75.8，经验置信区间（ECI）66.5 - 83.5]；基线血清肌酐（SCr）（AUC = 72.0，ECI 65.7 - 78.7）；LVEF（AUC = 67.6，ECI 58.4 - 75.8）；以及呋塞米等效利尿剂量（AUC = 66.0，ECI 57.5 - 74.6）。同样，SGLT2i停药的最强阳性预测模型是糖化血红蛋白A1C（AUC = 81.1，ECI 74.8 - 87.2）；基线SCr（AUC = 67.4，ECI 58.7 - 75.5）；LVEF（AUC = 68.7，ECI 58.9 - 76.5）；以及呋塞米等效利尿剂量（AUC = 67.2，ECI 58.2 - 76.0）。
糖化血红蛋白A1C是HFrEF患者开始使用SGLT2i后发生AKI和停药的最强预测模型。糖尿可能与此效应有关。基线SCr较高且襻利尿剂剂量较高的患者发生这些结局的风险可能更大。未来需要进行前瞻性研究，以进一步评估这些发现以及AKI和SGLT2i停药的其他预测模型，以指导SGLT2抑制剂的临床应用。
