Efficacy and safety of nafamostat mesilate for anticoagulation during ECMO/CRRT: insight from the integrated meta-analysis and FAERS pharmacovigilance study.

Background: Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) require a balance between maintaining circuit patency and minimizing bleeding risk. Nafamostat mesilate (NM) is a short-acting anticoagulant with distinctive pharmacokinetic properties, including rapid metabolism and a short half-life, which may reduce prolonged systemic anticoagulant exposure. These characteristics make NM a potential alternative to conventional anticoagulation strategies, particularly for patients at high risk of bleeding. This study aimed to systematically evaluate the efficacy and safety of NM as an anticoagulant for ECMO/CRRT. Methods: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data were systematically searched for randomized controlled trials and cohort studies comparing NM with sodium citrate, unfractionated heparin (UFH), or no anticoagulation. A meta-analysis was conducted to evaluate filter lifespan, bleeding events, thromboembolic events, and 28-day/intensive care unit (ICU) mortality. Reporting characteristics and potential safety signals for the three anticoagulants were also compared using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Results: The meta-analysis included 17 studies involving 1,893 patients. Filter lifespan did not differ significantly between the NM and control groups (mean difference [MD] = 1.29 h; 95% confidence interval [CI], -1.09-3.66), whereas the risk of bleeding events was significantly lower in the NM group (odds ratio [OR] = 0.61; 95% CI, 0.43-0.86). Subgroup analyses showed that NM was associated with a significantly lower risk of bleeding than sodium citrate (OR = 0.53; 95% CI, 0.31-0.90) and no anticoagulation (OR = 0.41; 95% CI, 0.19-0.90); sensitivity analyses supported the robustness of this finding. The FAERS analysis included 24,238 reports, comprising 233 for NM, 1,612 for sodium citrate, and 22,393 for UFH, with distinct reporting profiles observed among the three anticoagulants. Representative signals for NM included disseminated intravascular coagulation (n = 17; ROR = 112.68, 95% CI: 69.69-182.19), gastrointestinal hemorrhage (n = 12; ROR = 15.44, 95% CI: 8.74-27.29), and decreased platelet count (n = 13; ROR = 7.52, 95% CI: 4.35-13.00). Conclusion: NM may reduce bleeding risk while maintaining a filter lifespan comparable to that achieved with other anticoagulation strategies, potentially providing an individualized anticoagulation option for patients at high risk of bleeding. In clinical practice, coagulation abnormalities, changes in platelet counts, and bleeding-related events should be closely monitored.