The anticoagulation field is experiencing a renaissance that began with regulatory approval of the direct thrombin inhibitor dabigatran, a direct oral anticoagulant (DOAC), in 2010. The DOAC medication class has rapidly evolved to include the additional approval of 4 direct factor Xa inhibitors. Commensurately, DOAC use has increased and collectively account for the majority of new anticoagulant prescriptions. Despite exclusion of patients with moderate-to-severe kidney disease from most pivotal DOAC trials, DOACs are increasingly used in this setting. An advantage of DOACs is similar or improved antithrombotic efficacy with less bleeding risk when compared with traditional agents. Several post hoc analyses, retrospective studies, claims data studies, and meta-analyses suggest that these benefits extend to patients with kidney disease. However, the lack of randomized controlled trial data in specific kidney disease settings, with their unique pathophysiology, should be a call to action for the kidney community to systematically study these agents, especially because early data suggest that DOACs may pose less risk of anticoagulant-related nephropathy than do vitamin K antagonists. Most DOACs are renally cleared and are significantly protein bound in circulation; thus, the pharmacokinetics of these drugs are influenced by reduced renal function and proteinuria. DOACs are susceptible to altered metabolism by P-glycoprotein inhibitors and inducers, including drugs commonly used for the management of kidney disease comorbidities. We summarize the currently available literature on DOAC use in kidney disease and illustrate knowledge gaps that represent important opportunities for prospective investigation.
Bibliographical noteFunding Information:
MNR is a site primary investigator in clinical trials for Retrophin, Advicenne, Reata, and Genentech and has received research funding from Goldfinch Bio, Novartis, National Institute of Diabetes and Digestive and Kidney Diseases, and Department of Defense unrelated to direct oral anticoagulants. VKD has received consultant fees from Novartis and Retrophin and honoraria from RTI International and UpToDate unrelated to direct oral anticoagulants. VKD is, or has been, a site primary investigator in multiple clinical trials for Mallinckrodt, Gilead, Bristol-Myers Squibb, InflaRx, ChemoCentryx, Otsuka, and Retrophin. BAK has received research funding from Novo Nordisk A/S and CSL Behring unrelated to direct oral anticoagulants. BAK is, or has been, a site primary investigator in multiple clinical trials for Bayer Healthcare, CSL Behring, Novo Nordisk A/S, and Bioverativ and has received consultant fees or honoraria from Bayer Healthcare, Novo Nordisk A/S, and CSL Behring.
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (award numbers K08DK103982 and R03DK118315 to BAK and award numbers U54DK083912 and P01DK058335 to VKD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- atrial fibrillation
- chronic kidney disease
- end-stage kidney disease
- lupus nephritis
- nephrotic syndrome
- venous thromboembolism
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural