Major Bleeding and Hemorrhagic Stroke with Direct Oral Anticoagulants in Patients with Renal Failure Systematic Review and Meta-analysis of Randomized Trials

Background: Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined.

Methods: A systematic review was performed assessing the reported safety of DOACs compared to vitamin K antagonists (VKA) in patients with RF, creatinine clearance (eCrCL) <50mL/min and [eCrCL] 50-80 mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTials.gov) were searched for Randomized clinical trials up to Nov 2015. The data were pooled using both traditional frequentist and Bayesian random-effects models.

Results: Nine trials met inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared to VKA, DOACs were associated with a significantly decreased risk for major bleeding in patients with [eCrCL] 50-80 mL/min (risk ratio [RR] 0.84; 95% CI, 0.78-0.91), and a non-significant decrease in the risk for major bleeding in patients with eCrCL <50mL/min (RR, 0.80; 95% CI, 0.63-1.01), with evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared to other DOACs in patients with eCrCL <50mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared to VKA in pateints with [eCrCL] <50mL/min and 50-80mL/min.

Conclusions: As a class, DOACs are associated with reduced risk for hemorrhagic stroke in patients with RF compared to VKA. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL <50mL/min.

PROSPERO registry- CRD42014013730

Disclosures: The authors have no conflicts of interest to disclose