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.