Anticoagulant risks may outweigh benefits for those on dialysis with atrial fibrillation
For patients with kidney failure and nonvalvular atrial fibrillation, treatment with apixaban did not lead to a reduced incidence of stroke. The drug was, however, associated with a higher incidence of fatal or intracranial bleeding.
According to Thomas A. Mavrakanas, MD, of Brigham & Women’s Hospital at Harvard Medical School, and colleagues, apixaban is the most commonly used direct oral anticoagulant for patients undergoing maintenance dialysis in the United States despite that it has lower elimination by the kidneys compared with similar medications.
“Appropriate dose adjustment may be an issue because the drug accumulates with prolonged use, with the standard dose leading to supratherapeutic drug levels in some patients on hemodialysis and the reduced dose leading to drug levels at the lower range of the therapeutic interval,” the researchers wrote.
Coupled with data that suggest warfarin is ineffective in preventing either stroke or systemic thromboembolism, as well as studies demonstrating high bleeding event rates associated with anticoagulation in this patient population, Mavrakanas and colleagues argued “it is critical to assess the relative efficacy and safety of apixaban compared with no anticoagulation before advocating for its use in patients receiving maintenance dialysis.”
To do this, the researchers compared outcomes between 521 patients treated with apixaban and 1,561 patients who received no anticoagulation therapy, matching for baseline characteristics. Patients taking apixaban were further categorized based on dosing regimen (standard: 5 mg twice daily; low: 2.5 mg twice daily).
Findings indicated apixaban was not associated with a lower incidence of hospital admission for a new stroke (ischemic or hemorrhagic), transient ischemic attack or systemic thromboembolism (hazard ratio = 1.24) compared with no anticoagulant.
In addition, researchers observed a significantly higher incidence of fatal or intracranial bleeding in patients treated with apixaban (HR = 2.74).
When considering outcomes based on dose, the researchers found the standard dose of apixaban to be associated with a significantly higher incidence of stroke, transient ischemic attack, systemic thromboembolism, and fatal or intracranial bleeding events compared with no treatment. These results were not observed for patients on the reduced dose.
The researchers noted apixaban users did appear to have a lower incidence of all-cause mortality, but suggested this is due to “selection bias, with ‘healthier’ patients being prescribed apixaban and between-group differences not fully accounted for despite propensity-score matching and adjustment for stroke or bleeding risk scores.”
In addition to trials determining whether apixaban should be utilized for reducing mortality risk, they recommended a randomized trial comparing both apixaban doses with no anticoagulation should be conducted.
“Awaiting randomized data, prudence in prescribing apixaban to patients on maintenance dialysis, especially at the standard dose, is warranted,” they concluded.