Direct oral anticoagulants (DOACs) may be a safer alternative to warfarin even among patients with chronic kidney disease (CKD) or kidney failure, investigators suggest.

Wei Ling Lau, MD, and colleagues from the University of California Irvine in Orange, studied 351,407 patients on anticoagulation therapy identified using the OptumLabs Data Warehouse. Of these patients, 45% received DOACs and 55% received warfarin, predominantly for atrial fibrillation (AF; 44%), deep vein thrombosis (DVT; 23%), and pulmonary embolism (PE; 13%). Approximately 42,000 patients (12% of the entire cohort) had CKD stage 3 to 5 or end-stage kidney disease (ESKD).

Use of DOACs vs warfarin was significantly associated with a 22% lower risk of the cardiovascular combination endpoint of myocardial infarction and ischemic stroke and a 10% lower risk of bleeding in adjusted analyses, the investigators reported in the American Journal of Nephrology. By subgroup, DOACs were significantly associated with an 8% lower risk of bleeding in patients without CKD and  a 10%, 22%, and 19% lower risk of bleeding in patients with CKD stage 3, stage 4 and 5, and ESKD, respectively.

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Using DOACs rather than warfarin for AF was associated with lower risks of the cardiovascular endpoint and bleeding across all CKD stages. The investigators observed no significant differences for other indications, such as DVT, PE, and arterial embolism.

According to Dr Lau’s team, “the results of our study provide further evidence that DOACs may be safer than warfarin in CKD and ESKD patients, though it remains unclear if DOACs are safer for other anticoagulation indications aside from AF.”

In this study, 30% of DOAC users received apixaban, 59% rivaroxaban, 0.1% edoxaban, and 10% dabigatran. Apixaban has been approved for use in patients receiving hemodialysis, but thus far rivaroxaban, edoxaban, and dabigatran have not. The investigators acknowledged that data from randomized, placebo-controlled trials are still needed.


Sy J, Hsiung J-T, Edgett D, Kalantar-Zadeh K, Streja E, Lau WL. Cardiovascular and bleeding outcomes with anticoagulants across kidney disease stages: analysis of a national US cohort. Am J Nephrol. Published online March 31, 2021. doi:10.1159/000514753