Clinical question: How safe are direct oral anticoagulants (DOACs) to use in kidney dysfunction?
Background: DOACs are increasingly being used in patients with kidney dysfunction. DOACs are cleared, at least in part, renally. Guidelines suggest dose reduction when additional factors are present. However, patients with kidney dysfunction may also receive reduced doses due to clinicians’ concerns for major bleeding. This study assesses the safety of DOACs along the continuum of renal function.
Study design: Patient-level meta-analysis
Setting: Multiple sites, four major studies reviewed
Synopsis: This meta-analysis used the COMBINE AF database. COMBINE AF (Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) uses data from well-known studies: RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48. In this study of 71,683 patients, the mean CrCl was 75.5 ml/min. As expected, the incidence of stroke or systemic embolism, major bleeding or intracranial hemorrhage (ICH), and death increased with worsening kidney function. The hazard of major bleeding did not change across continuous CrCl values down to 25 ml/min in patients randomized to standard dose DOAC as compared to warfarin (P for interaction=.61). Compared to warfarin, standard dose DOAC use resulted in a significantly lower hazard of ICH (6.2% decrease in hazard ratio per 10 ml/min decrease in CrCl). Use of a lower dose rather than standard dose DOAC was not associated with a significant difference in incident bleeding or ICH in patients with reduced kidney function but was associated with a higher incidence of death and stroke or systemic embolism.
Bottom line: Standard dose DOACs appear safe for most patients up to CrCl of 25. In the absence of contraindication, patients with atrial fibrillation and a CrCl down to 25 mL/min should receive a standard DOAC, with dose adjustment only as specified in trials or guidelines, rather than warfarin or a lower dose DOAC, to reduce the risk for stroke and/or death. A limitation of this study is that patients with CrCl of <30ml/min were only 0.7% percent of the study population. Additionally, of the two commonly used DOACs, apixaban was used more commonly in lower renal function than rivaroxaban in the study population.
Citation: Harrington J, et al. Direct oral anticoagulants versus warfarin across the spectrum of kidney function: Patient-level network meta-analyses from COMBINE AF. Circulation. 2023;147(23):1748-57.
Dr. Tollera
Dr. Tollera is a hospitalist at Advocate Health in Milwaukee, Wis.