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.

Abstract

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.

• Authors: Xiaole Su, Bingjuan Yan, Lihua Wang, Hong Cheng, Yipu Chen
• Journal: BMJ open (BMJ Open) Vol. 12 Issue 2 Pg. e048619 (Feb 21 2022) ISSN: 2044-6055 [Electronic] England
• PMID: 35190410 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Anticoagulants

Topics

• Administration, Oral
• Anticoagulants (adverse effects)
• Humans
• Kidney (physiopathology)
• Network Meta-Analysis
• Venous Thromboembolism (drug therapy, physiopathology)