Direct anticoagulants associated with increased risk of bleeding

Results of a study suggest the need for caution in the prescription of direct oral anticoagulants for patients with chronic kidney disease (CKD).

Researchers at Johns Hopkins University identified certain blood thinners, called direct oral anticoagulants, with approval to treat atrial fibrillation, that may put patients with CKD at a higher risk of bleeding.

These drugs are cleared by the kidney to a certain extent, with their elimination slower in patients with CKD. Due to the slower removal of these blood thinners, these patients may be predisposed to drug accumulation, resulting in a higher risk of bleeding.

To explore this hypothesis, Dr Jung-Im Shin and her colleagues examined data from the electronic health records from 2010 to 2017, of 3206 patients with atrial fibrillation who used direct oral anticoagulants, and 3206 patients with atrial fibrillation who used the conventional anticoagulant warfarin.

Over 7391 person-years (the number of follow up years multiplied by the number of people in the study), there were 1181 bleeding event and 466 ischemic strokes.

Results showed that in patients without CKD, the risk of bleeding and the advantage of the prevention of ischemic stroke were similar between those who used warfarin and those using direct anticoagulants.

In patients with CKD, there was an increased risk of bleeding by 23 percent if direct anticoagulants were taken, in comparison with warfarin. There were similar benefits from prevention of ischemic strokes.

“Despite sparse evidence in safety and effectiveness of direct oral anticoagulants in CKD, we saw that prescription of direct oral anticoagulants in the CKD population increased substantially over time. We also found that direct oral anticoagulant use was linked with a higher risk of bleeding compared to warfarin use in patients with CKD.” said Dr. Shin.

Regardless of the exclusion of CKD patients in all randomised clinical trials of direct anticoagulants, the drugs have been approved for use for these patients by the U.S. Food and Drug Administration (FDA).

Considering approximately one-quarter of patients with atrial fibrillation have CKD, the actual safety and effectiveness of direct anticoagulants for patients with kidney disease seems pivotal.

Results will be published in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN).