Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients: a systematic review and meta-analysis

Abstract

Background: Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT).

Methods: The Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies.

Results: Four randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = -10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution.

Conclusion: Given the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.

Keywords: COVID-19; Nafamostat mesilate; bleeding complication; blood purification; mortality.

Figure 1.

Study inclusion flow chart.

Figure 2.

Risk of bias and summary of the risk of bias of 4 enrolled RCTs.

Figure 3.

Forest plots of comparisons: CT versus NM; Outcomes: bleeding complications.

Figure 4.

Forest plots of comparisons: subgroups of CT versus NM; Outcomes: bleeding complications.

Figure 5.

Forest plots of comparisons: CT versus NM; Outcomes: In-hospital mortality.

Figure 6.

Forest plots of comparisons: subgroups of CT versus NM. Outcomes: In-hospital mortality under the fixed-effect model (A) and under the random-effect model (B).

Figure 7.

Forest plots of comparisons: CT versus NM. Outcomes: hemofilter lifespan.

Figure 8.

Sensitivity analysis shows the meta-analysis has satisfactory stability on bleeding complication (A) and in-hospital mortality (B); Egger (C) and Begg (D) tests for In-Hospital Mortality; Egger (E) and Begg (F) tests for bleeding complications.