Kato Takahiro, Nakano Yusuke, Yasukawa Noriko, Oonishi Masafumi, Hamada Yukihiro
Department of Pharmacy, Kochi Medical School Hospital, Kochi, Japan.
Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Aichi, Japan.
Ren Fail. 2025 Dec;47(1):2538830. doi: 10.1080/0886022X.2025.2538830. Epub 2025 Aug 21.
To evaluate the dose-dependent renoprotective effects of sacubitril/valsartan in heart failure patients. This retrospective observational study included patients with heart failure (Stage B or higher, B-type natriuretic peptide (BNP) >100 pg/mL or N-terminal proBNP >300 pg/mL) who initiated sacubitril/valsartan (SV) treatment. Patients were classified by final SV daily dose (50, 100, 200, or 400 mg) at 18 months. Factors associated with eGFR changes were identified using multiple regression analysis. A total of 157 patients (mean age 74.8-77.9 years, 64.3% male) were stratified by daily SV dosage groups (50 mg, = 20; 100 mg, = 46; 200 mg, = 62; 400 mg, = 29). Baseline characteristics were similar across groups for eGFR, heart failure stage, diabetes history, myocardial infarction, atrial fibrillation, proteinuria, and use of most heart failure medications. However, hypertension prevalence and systolic blood pressure differed significantly between groups ( < 0.05). One-way ANOVA revealed significant dose-dependent differences in eGFR changes among SV dosage groups ( < 0.05). In the final multiple linear regression model, SV dosage ( < 0.05) was a significant factor associated with eGFR changes, with proteinuria showing a trend toward significance. Sex and BNP levels ≥400 pg/dL were not significant. Sensitivity analysis converting SV dosage to a categorical variable confirmed these findings. Stratification by proteinuria status demonstrated dose-dependent relationships in both proteinuria-positive and proteinuria-negative subgroups, with more pronounced dose dependency in the proteinuria-positive group ( < 0.001). SV exhibits dose-dependent renoprotective effects in heart failure patients. Optimizing SV dosage may be beneficial for heart failure patients with concurrent kidney dysfunction, especially those with proteinuria.
评估沙库巴曲缬沙坦对心力衰竭患者的剂量依赖性肾脏保护作用。这项回顾性观察性研究纳入了开始接受沙库巴曲缬沙坦（SV）治疗的心力衰竭患者（B期或更高分期，B型利钠肽（BNP）>100 pg/mL或N末端前脑钠肽>300 pg/mL）。患者根据18个月时的最终SV每日剂量（50、100、200或400 mg）进行分类。使用多元回归分析确定与估算肾小球滤过率（eGFR）变化相关的因素。共有157例患者（平均年龄74.8 - 77.9岁，64.3%为男性）按SV每日剂量组分层（50 mg，n = 20；100 mg，n = 46；200 mg，n = 62；400 mg，n = 29）。各剂量组在eGFR、心力衰竭分期、糖尿病史、心肌梗死、心房颤动、蛋白尿以及大多数心力衰竭药物的使用情况等基线特征方面相似。然而，高血压患病率和收缩压在各剂量组之间存在显著差异（P < 0.05）。单因素方差分析显示，SV剂量组之间eGFR变化存在显著的剂量依赖性差异（P < 0.05）。在最终的多元线性回归模型中，SV剂量（P < 0.05）是与eGFR变化相关的显著因素，蛋白尿呈现出显著趋势。性别和BNP水平≥400 pg/dL不显著。将SV剂量转换为分类变量的敏感性分析证实了这些结果。按蛋白尿状态分层显示，蛋白尿阳性和阴性亚组均存在剂量依赖性关系，蛋白尿阳性组的剂量依赖性更为明显（P < 0.001）。沙库巴曲缬沙坦在心力衰竭患者中表现出剂量依赖性肾脏保护作用。优化沙库巴曲缬沙坦剂量可能对合并肾功能不全的心力衰竭患者有益，尤其是那些有蛋白尿的患者。
