Abstract / Summary
Major surgical procedures are associated with significant blood loss, which may necessitate transfusions and increase the risk of post-operative complications. Tranexamic acid (TXA) and aminocaproic acid (EACA) are commonly used antifibrinolytic agents across various surgical specialties, including orthopaedic, cardiac, spinal, and hepatic surgery. The comparative efficacy of these agents is not well established, and this meta-analysis provides a comprehensive evaluation of TXA versus EACA in major surgical procedures. The study was conducted in accordance with the PRISMA guidelines. A systematic literature search was conducted using Cochrane, PubMed and Embase from database inception to 1 October 2025 to find articles discussing the comparison between TXA and EACA in patients undergoing major surgery. The primary outcomes were total blood loss (ml) and 24-hour blood loss (ml). Secondary outcomes included requirements for transfusions and following adverse events. RoB2 method was utilised to evaluate risk of bias and the ROBVIS tool allowed a graphical summary for each study. Mean differences (MD) with 95% CI quantified continuous outcomes, and Risk Ratios (RR) with 95% CI were outlined for dichotomous outcomes. A major limitation of the primary analysis is the pooling of different surgical types (orthopaedic, cardiac, spinal, and hepatic), each with distinct bleeding profiles and blood loss metrics; this heterogeneity is addressed through subgroup analyses. The meta-analysis included 9 RCTs, where data from these studies were used for various outcomes. Sensitivity analyses demonstrated that the findings were generally consistent across various assumptions and data transformation method. Total blood loss was significantly lower with TXA compared to EACA (MD -147.16 ml; 95% CI: -241.46 to -52.85; p = 0.002). However, analysis of 24-hour blood loss from 5 studies showed no statistically significant difference between the two agents (MD -62.63 ml; p = 0.07). Subgroup analysis of cardiac surgeries showed no significant difference between TXA and EACA (MD -10.88 ml; p = 0.81); however, a larger dedicated cardiac meta-analysis has reported a significant reduction in 24-hour blood loss favouring TXA. Among secondary safety outcomes, most showed no significant differences between the two agents. However, renal dysfunction was significantly lower with TXA compared to EACA (RR 0.42, 95% CI 0.19–0.90; p = 0.03), though this finding is based on limited data and warrants cautious interpretation. TXA is more effective than EACA in reducing total blood loss specifically in orthopaedic surgeries, with the most consistent evidence observed in total knee arthroplasty, though this finding is based on a limited number of trials. In cardiac surgery, our limited subgroup analysis did not detect a difference, although a larger cardiac-specific meta-analysis favours TXA; further procedure-specific RCTs are warranted. Despite the reduction in total blood loss, TXA was associated with a significantly higher proportion of patients requiring RBC transfusion—a finding that likely reflects variable transfusion thresholds rather than a true pharmacological effect. These findings are most applicable to orthopaedic settings, and further specialty-specific RCTs are needed to clarify efficacy in spinal, hepatic, and other major surgical procedures. Most secondary safety outcomes showed no significant differences, though renal dysfunction was significantly lower with TXA in a single study; these findings should be interpreted cautiously given the limited number of events. Narrative data from primary studies suggest EACA may be less expensive in terms of drug acquisition costs, though formal economic analysis was not performed. This meta-analysis provides a foundation for future investigation, highlighting the need for further RCTs.