The Role of Anticoagulants in Patients with Advanced Liver Disease: A Systematic Review and Network Meta-Analysis

Introduction: Our main aim for the study is to measure the efficacy and safety of different anticoagulants in patients with advanced liver disease. Methods: We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The quality assessment of the included randomized controlled trials was conducted through Cochrane Tool, while the quality of the included cohort studies was assessed by the NIH tool. The network meta-analysis was performed through the R software. Results: We included 54 studies with 91218 patients, The results showed a significant variation in cases of DOACs compared with UnFractioned Heparin in the lower risk of major bleeding (relative risk (RR)= 0.03) with another significantly lower risk in DOACs compared with low molecular-weight heparin (LMWH) (RR= 0.39) with another significantly lower risk in direct oral anticoagulants (DOAC) compared with warfarin or LMWH (RR= 0.48), The results showed no significant variation between fondaparinux and warfarin (RR= 0.85), On the other hand, warfarin showed a significantly lower risk of major bleeding compared to LMWH and UFH respectively (RR= 0.48) and (RR= 0.04). The recurrence of thrombosis was significantly decreased with the use of DOACs; when compared with (Warfarin or LMWH) (RR= 0.38), was also significant when compared with control (RR= 0.28), and was significant when compared with LMWH ( RR= 0.11). The results showed a significant decrease in the recurrence of thrombosis when patients use LMWH and Warfarin together in comparison with control and LMWH alone respectively ( RR= 0.38), ( RR= 0.15). The results showed a significant decrease in the recurrence of thrombosis when patients use warfarin in comparison with control ( RR= 0.41, 95% CI [0.21; 0.82]). Also, The recurrence of thrombosis was significantly decreased with the use of (LMWH and acenocoumarol); when compared with with control (RR= 0.09), and was significant when compared with LMWH alone (RR= 0.03). Conclusion: Our meta-network study found that DOACs showed the least major incidence of major bleeds, especially when compared with vitamin K antagonists (VKAs). The most significant results in decreasing the progression of thrombosis were LMWH and Acenocoumarol followed by DOACs which showed better results compared to VKA (Figure 1).Figure 1.: Recurrence or progression of thrombosis (A) Network graph showing direct evidence between the evaluated drugs. (B) A forest plot comparing all drugs with control. (C) The league table represents the network meta-analysis estimates for all drugs' comparisons.