Safety and efficacy of direct oral anticoagulants in chronic kidney disease: a meta-analysis

Abstract

Background: Direct oral anticoagulants (DOACs) have emerged as the first-line therapy for venous thromboembolism and stroke prophylaxis in atrial fibrillation. As DOACs are partially excreted renally, their safety in patients with chronic kidney disease (CKD) is unclear. Objectives: To synthesize primary evidence on the safety profile of DOACs in patients with CKD. Methods: We searched MEDLINE and Embase from inception to June 2023 for randomized and nonrandomized cohort studies comparing DOACs with vitamin K antagonists (VKAs) in CKD patients. Screening and data collection were conducted in duplicate. The primary safety outcome was major bleeding, defined by International Society on Thrombosis and Haemostasis criteria, stratified by CKD severity. Meta-analysis was done using the Mantel–Haenszel random-effects model, presented as odds ratios (ORs) with corresponding 95% CIs. Results: Of the 2355 articles captured in the literature search, 25 nonrandomized studies (n = 6832) and 6 randomized studies (n = 66,898) were included. DOACs reduced major bleeding compared with VKAs in all subgroups (stage 4: OR, 0.73; 95% CI, 0.58, 0.93; stage 5/renal replacement therapy: OR, 0.70; 95% CI, 0.50, 0.98; stage unspecified: OR, 0.72; 95% CI, 0.63, 0.83). Apixaban and rivaroxaban both reduced major bleeding in stage 5/renal replacement therapy patients (apixaban: OR, 0.66; 95% CI, 0.52, 0.85; rivaroxaban: OR, 0.58; 95% CI, 0.35, 0.94). Conclusion: In this meta-analysis, DOACs reduced major bleeding compared with VKAs in stage 4, stage 5/renal replacement therapy, and CKD stage unspecified patients. Future analysis should evaluate the impact of specific DOACs and dosage on safety and efficacy in this population.

Keywords

• chronic
• factor Xa inhibitors
• hemorrhage
• renal insufficiency
• venous thromboembolism
• warfarin