High Bleeding Risk with 5mg Apixaban among patients with Atrial Fibrillation with CKD compared to lower dose

A recent study published in the Circulation Journal found the potential risks and benefits associated with different doses of apixaban in patients suffering from atrial fibrillation (AF) and severe chronic kidney disease (CKD). The research, conducted using electronic health record data from the Optum Labs Data Warehouse, focused on comparing the risks of bleeding and stroke/systemic embolism between two dosages of apixaban, 5 mg, and 2.5 mg.

The study identified 4,313 new apixaban users with AF and CKD stage 4/5 who started treatment between 2013 and 2021. The researchers adjusted for baseline characteristics using inverse probability of treatment weighting and employed statistical models to account for the competing risk of death.

Among the patients, 40% received the 5 mg apixaban dose, while 60% received the 2.5 mg dose. Patients on the higher 5 mg dose were generally younger, had a greater body weight, and higher serum creatinine levels. However, there was no significant difference in mean estimated glomerular filtration rate between the two groups.

In the analysis, it was found that the 5 mg apixaban dose was associated with a higher risk of bleeding, with an incidence rate of 4.9 events per 100 person-years compared to 2.9 events per 100 person-years for the 2.5 mg dose. This translated to an incidence rate difference of 2.0 events per 100 person-years and a subdistribution hazard ratio of 1.63.

However, there was no significant difference between the two doses regarding the risk of stroke/systemic embolism or death. The incidence rates for these outcomes were similar in both groups.

The authors concluded that in patients with AF and severe CKD, the use of the 5 mg apixaban dose was associated with a higher risk of bleeding compared to the 2.5 mg dose. This finding aligns with dosing recommendations from the KDIGO Guidelines and the European Medicines Agency, which suggest lower doses for this population. These recommendations differ from those issued by the US Food and Drug Administration.

This observational study highlights a 1.6 times higher risk of bleeding with the 5 mg apixaban dose compared to the 2.5 mg dose in AF patients with severe CKD. While no significant differences were observed in stroke/systemic embolism or death, the results suggest that the lower dose may be a safer choice for this patient population.

Reference:

Xu, Y., Chang, A. R., Inker, L. A., McAdams-DeMarco, M., Grams, M. E., & Shin, J.-I. (2023). Associations of Apixaban Dose With Safety and Effectiveness Outcomes in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease. In Circulation. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/circulationaha.123.065614