Supplementary Material for: Comparison of Anticoagulant Effects of Nafamostat Mesilate and Heparin in Continuous Renal Replacement Therapy for Patients with High Bleeding Risk：A Meta- Analysis Systemic Review

Objectives: To evaluate the effects of Nafamostat versus heparin on anticoagulation efficacy, filter lifespan, bleeding and other adverse events in patients with high bleeding risk undergoing continuous renal replacement therapy.
Methods: Computerized retrieval was conducted in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, and VIP databases for relevant English or Chinese studies published since their establishment until June 22, 2025. Thirteen studies comparing Nafamostat with heparin for patients with high bleeding risk during continuous renal replacement therapy were included. Two researchers independently performed literature screening, data extraction, and evaluation of literature quality. Meta-analysis was conducted using Stata 18 software.
Results: A total of 11 observational studies were included in this research, involving 1,354 patients. The meta-analysis results showed that Nafamostat significantly reduced the risk of bleeding compared to heparin [RR = 0.38, 95% CI (0.20, 0.74), P < 0.05], but there were no statistically significant differences in filter lifespan [SMD = -0.01, 95% CI (-0.50, 0.48), P = 0.053], coagulation events [RR = 0.92, 95% CI (0.33, 2.54), P = 0.868], and mortality [RR = 1.20, 95% CI (0.87, 1.66), P = 0.256]. The subgroup analysis comparing the Nafamostat group to the heparin group showed that NM significantly reduced the risk of bleeding compared to LMWH [RR = 0.20, 95% CI (0.06, 0.71), P = 0.013], while the bleeding risk in the unfractionated heparin group [RR = 0.46, 95% CI (0.20, 0.74), P = 0.071] showed a downward trend but did not reach statistical significance. Patients with platelet counts < 100×10⁹/L [RR = 0.25, 95% CI (0.07, 0.88), P = 0.031] had significantly lower bleeding risk compared to those with platelet counts ≥ 100×10⁹/L [RR = 0.48, 95% CI (0.19, 1.22), P = 0.121].
Conclusion: This systematic review and meta-analysis indicate that in patients with a high risk of bleeding who receive continuous renal replacement therapy (CRRT), Nafamostat has similar anticoagulant efficacy to heparin and can effectively maintain the patency of the extracorporeal circulation tubing. Moreover, Nafamostat significantly reduces the risk of bleeding. Therefore, for CRRT patients with a high risk of bleeding, it is recommended to prioritize the use of Nafamostat as the first-line anticoagulation regimen.

研究目的：评价萘莫司他（Nafamostat）与肝素用于高出血风险连续性肾脏替代治疗（CRRT）患者时的抗凝疗效、滤器使用寿命、出血事件及其他不良事件发生情况。
检索方法：计算机检索PubMed、Web of Science、Cochrane图书馆、Embase、中国知网（CNKI）、万方数据知识服务平台、维普网自建库以来至2025年6月22日发表的相关英文及中文研究。最终纳入13项对比高出血风险CRRT患者应用萘莫司他与肝素抗凝效果的研究。由2名研究者独立完成文献筛选、数据提取及文献质量评价，采用Stata 18软件进行Meta分析。
研究结果：本研究最终纳入11项观察性研究，共涉及1354例患者。Meta分析结果显示：相较于肝素，萘莫司他可显著降低出血风险[相对危险度（RR）=0.38，95%置信区间（CI）(0.20, 0.74)，P<0.05]；但在滤器使用寿命[标准化均数差（SMD）=-0.01，95%CI(-0.50, 0.48)，P=0.053]、凝血事件[RR=0.92，95%CI(0.33, 2.54)，P=0.868]及病死率[RR=1.20，95%CI(0.87, 1.66)，P=0.256]方面，两组差异无统计学意义。亚组分析显示：相较于低分子肝素（LMWH），萘莫司他可显著降低出血风险[RR=0.20，95%CI(0.06, 0.71)，P=0.013]；而相较于普通肝素，萘莫司他组出血风险虽呈下降趋势[RR=0.46，95%CI(0.20, 0.74)，P=0.071]，但未达到统计学显著性。血小板计数<100×10⁹/L的患者[RR=0.25，95%CI(0.07, 0.88)，P=0.031]，其出血风险显著低于血小板计数≥100×10⁹/L的患者[RR=0.48，95%CI(0.19, 1.22)，P=0.121]。
结论：本系统评价及Meta分析结果显示，对于接受连续性肾脏替代治疗（CRRT）的高出血风险患者，萘莫司他与肝素的抗凝疗效相当，可有效维持体外循环管路通畅；同时，萘莫司他可显著降低患者出血风险。因此，推荐高出血风险CRRT患者优先选用萘莫司他作为一线抗凝方案。