Clinical question: Is the use of standard-dose apixaban based on creatinine criteria placing patients at higher risk of bleeding?
Background: The U.S. Food and Drug Administration recommends apixaban dose reduction if a patient with renal dysfunction also meets at least one of either weight or age criteria. On the other hand, the European Medicines Agency indicates the reduced dose of apixaban for patients with CrCl 15 to 30 mL/min. Based on the creatinine criteria, up to 40% of patients with CrCl below 30ml/min may be prescribed standard dose apixaban. Does this put them at increased risk of bleeding?
Study design: Retrospective cohort
Setting: 40 health systems in the U.S. participating in Optum Lab Data Warehouse
Synopsis: Among 4,313 apixaban new users, 1,705 (40%) received 5 mg and 2,608 (60%) received 2.5 mg. Patients treated with 5 mg apixaban were younger (mean age, 72 versus 80 years), with greater weight (95 versus 80 kg) and higher serum creatinine (2.7 versus 2.5 mg/dL). The mean estimated glomerular filtration rate was not different between the groups (24 versus 24 mL/min/1.73 m2). The study authors report that, in patients with CKD 4 or 5, there was a 1.6 times increased risk of bleeding [95% CI, 1.04 to 2.54] with 5 mg apixaban versus 2.5 mg, without difference in stroke, systemic embolism, or death.
Bottom line: In advanced kidney disease (stage 4 or 5) not on hemodialysis, apixaban dose reduction appears reasonable due to the increased risk of bleeding without additional stroke or systemic embolism prevention benefits. This study supports recommendations by the European Medicines Agency.
Citation: Xu Y, et al. Associations of apixaban dose with safety and effectiveness outcomes in patients with atrial fibrillation and severe chronic kidney disease. Circulation. 2023;148(19):1445-54.
Dr. Tollera
Dr. Tollera is a hospitalist at Advocate Health in Milwaukee, Wis.