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.