Comparative efficacy and safety of oral anticoagulants for the treatment of venous thromboembolism in the patients with different renal functions: a systematic review, pairwise and network meta-analysis.

Objectives: To compare the efficacy and safety of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and different renal functions.

Design: Systematic review containing pairwise and Bayesian network meta-analysis of randomised controlled trials (RCTs).

Data Sources: MEDLINE, EMBASE and Cochrane Library.

Eligibility Criteria: RCTs reporting the efficacy and safety outcomes of DOACs in different creatinine clearance (CrCl) subgroups.

Data Extraction And Synthesis: Data extraction and quality assessment were undertaken by two independent reviewers. Data were pooled using the DerSimonian-Laird method in pairwise meta-analysis. Network meta-analysis within a Bayesian framework was conducted.

Results: Data from 10 RCTs were included. In the treatment of acute VTE, DOACs did not significantly reduce recurrent VTE or VTE-related death (OR, 0.96; 95% CI, 0.82 to 1.11) but significantly reduced bleeding events (0.76, 0.68 to 0.90) compared with warfarin. In the extended treatment of VTE, DOACs produced significant benefits in recurrent VTE or VTE-related death (0.23, 0.16 to 0.29), but significantly increased bleeding events (1.86, 1.04 to 3.33) compared with placebo/aspirin. There were no significant differences in efficacy and safety of DOACs among the three CrCl stratified subgroups in acute and extended treatment of VTE (p for subgroup heterogeneity >0.1). Bayesian network meta-analysis suggested that apixaban 2.5 mg and 5 mg two times per day were associated with a lower risk of bleeding than dabigatran, rivaroxaban, warfarin and aspirin in the subgroup with CrCl >80 mL/min.

Conclusions: For the treatment of acute VTE, DOACs are similar to warfarin in reducing recurrent VTE and VTE-related death but are significantly superior to warfarin in reducing the risk of bleeding. For the efficacy and safety of DOACs across different CrCl stratifications (30-50, 50-80 and more than 80 mL/min), no significant difference was found. In light of minimal evidence, apixaban might be associated with a lower risk of bleeding in patients with VTE and CrCl >80 mL/min.

Prospero Registration Number: CRD42018090896.