Supplementary Material for: Peridialytic Erythropoietin versus Roxadustat in Hemodialysis-dependent CKD Patients

Introduction
Erythropoietin and roxadustat are commonly used to manage anemia in hemodialysis-dependent chronic kidney disease (CKD) patients, but the comparative safety and effectiveness are unknown.
Methods
This is a retrospective cohort study. Data were extracted from Tianjin Healthcare and Medical Big Data Platform. We screened all patients with CKD stage G5 and anemia (hemoglobin <100 g/L) who were treated with either erythropoietin or roxadustat between January 1, 2015 and December 31, 2021. The primary endpoints included expanded composite of major adverse cardiovascular events (MACE+), cardiocerebrovascular events, and thromboembolic events in the peridialytic period, defined as the duration from the time of estimated glomerular filtration rate (eGFR) decrease to <15 mL/min•1.73 m2 to 3 months after dialysis initiation. A propensity score-matched analysis (1:1 ratio; caliper width: 0.02) was conducted to minimize the impact of confounding factors.
Results
The initial screen identified a total of 40,324 patients; 1092 were included in the propensity score-matched analysis (546 in each group). In comparison to the roxadustat group, the erythropoietin group had a lower rate of MACE+ events within 6 months (13.4% vs. 21.2%; P<0.001) and 12 months of treatment initiation (17.0% vs. 24.0%; P=0.004), as well as within 3 months of hemodialysis initiation (12.9% vs. 28.7%; P<0.001). The rate of cardiocerebrovascular events was also lower in the erythropoietin group within 6 months (38.5% vs. 50.7%, P<0.001) and 12 months of treatment initiation (49.1% vs. 56.2%, P<0.001). The rate of thromboembolic events did not differ between the two groups.
Conclusion
Peridialytic erythropoietin was associated with a more favorable cardiovascular safety profile versus roxadustat in hemodialysis-dependent CKD patients.

引言
促红细胞生成素和罗沙司他常用于管理依赖血液透析的慢性肾脏病（CKD）患者的贫血，但二者的安全性与有效性对比尚不明确。

方法
本研究为回顾性队列研究，数据来源于天津市卫生健康医疗大数据平台。我们筛选了2015年1月1日至2021年12月31日期间接受促红细胞生成素或罗沙司他治疗的CKD G5期贫血（血红蛋白<100 g/L）患者。主要终点包括透析过渡期内的主要不良心血管事件扩展复合终点（MACE+）、心脑血管事件及血栓栓塞事件；透析过渡期定义为估算肾小球滤过率（eGFR）降至<15 mL/min•1.73 m²至透析开始后3个月的时间段。采用倾向评分匹配分析（1:1配比；卡尺宽度：0.02）以最小化混杂因素的影响。

结果
初步筛选共识别出40324例患者，其中1092例纳入倾向评分匹配分析（每组各546例）。与罗沙司他组相比，促红细胞生成素组在治疗启动后6个月（13.4% vs. 21.2%；P<0.001）、12个月（17.0% vs. 24.0%；P=0.004）及血液透析启动后3个月内（12.9% vs. 28.7%；P<0.001）的MACE+事件发生率更低。促红细胞生成素组在治疗启动后6个月（38.5% vs. 50.7%，P<0.001）和12个月（49.1% vs. 56.2%，P<0.001）的心脑血管事件发生率亦显著降低。两组血栓栓塞事件发生率无统计学差异。

结论
在依赖血液透析的CKD患者中，透析过渡期使用促红细胞生成素相较于罗沙司他具有更优的心血管安全性特征。