Warfarin does not increase the risk of major bleeding in non-dialysis chronic kidney disease (CKD) patients who also have atrial fibrillation (AF), according to a new review and meta-analysis.

Investigators led by Chang-Sheng Ma, MD, of Beijing Tongren Hospital in China, examined 12 studies of warfarin use compared with warfarin “non-use” (i.e., low-dose warfarin, placebo, antiplatelet drugs, aspirin, or direct oral anticoagulants such as dabigatran, apixaban, and rivaroxaban) in patients with non-dialysis CKD and AF. The investigators looked for major bleeding events, including intracranial or extracranial hemorrhage and gastrointestinal hemorrhage, whether fatal or non-fatal.

An analysis of pooled data from 3 studies showed no significant difference in major bleeding risk from warfarin compared with placebo or antiplatelet drugs, according to results in Thrombosis Research, published online ahead of print. Information on aspirin was inadequate to determine relative risks.

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Direct oral anticoagulants (DOACs) actually reduced the risk of major bleeding by 19% according to an analysis of 3 randomized controlled trials. DOACs proved superior to warfarin even as renal function declined during mild to moderate CKD. “Therefore, we confirmed that DOACs were alternatives to warfarin for AF anticoagulation from the perspective of safety…” the researchers stated.

Reduced renal function is an independent risk factor for bleeding, so it remains important to monitor patients for worsening kidney function when DOACs are used. The benefits and risks of specific DOACs also need to be assessed.

Based on the available data, the investigators could not determine warfarin safety in patients with moderate to severe renal impairment. They also acknowledged an inability to distinguish the reason for major bleeding between poor timing of therapy and worsening renal function.


  1. Bai Y, Chen H, Yang Y, Liu XY, Shi XB, and Ma CS. Safety of Antithrombotic Drugs in Patients With Atrial Fibrillation and Non-end Stage Chronic Kidney Disease: Meta-analysis and Systematic Review. Thrombosis Research; doi: 10.1016/j.thromres.2015.11.020.