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Apixaban Dosing in Patients With AF and Severe CKD
Quick Takes
- This observational study reports a 1.6 times risk of bleeding with 5 mg apixaban (vs. 2.5 mg) twice daily in patients with AF and CKD stage 4/5, with no differences in stroke/systemic embolism or death.
- These findings suggest that 2.5 mg apixaban may be a better choice than 5 mg for patients with AF and severe CKD.
- Given several limitations of the current analysis and the unclear benefits of anticoagulation in severe CKD and AF, prospective RCTs are required to provide guidance on the decision to initiate anticoagulation and which anticoagulant and what dose to use in this population at very high risk for death.
Study Questions:
What are the risks for bleeding (potential harm) and stroke/systemic embolism (potential benefit) with two apixaban doses in patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD)?
Methods:
The investigators identified patients with AF and CKD stage 4/5 initiating apixaban between 2013 and 2021 with the use of deidentified electronic health record data from the Optum Labs Data Warehouse. Risks of bleeding and stroke/systemic embolism were compared by apixaban dose (5 vs. 2.5 mg), adjusted for baseline characteristics by the inverse probability of treatment weighting. The Fine-Gray subdistribution hazard model was used to account for the competing risk of death. Cox regression was used to examine risk of death by apixaban dose.
Results:
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 vs. 80 years), with greater weight (95 vs. 80 kg) and higher serum creatinine (2.7 vs. 2.5 mg/dL). Mean estimated glomerular filtration rate was not different between the groups (24 vs. 24 mL·min–1·1.73 m–2). In inverse probability of treatment weighting analysis, apixaban 5 mg was associated with a higher risk of bleeding (incidence rate 4.9 vs. 2.9 events per 100 person-years; incidence rate difference, 2.0 [95% CI, 0.6-3.4] events per 100 person-years; subdistribution hazard ratio, 1.63 [95% CI, 1.04-2.54]). There was no difference between apixaban 5 mg and 2.5 mg groups in the risk of stroke/systemic embolism (3.3 vs. 3.0 events per 100 person-years; incidence rate difference, 0.2 [95% CI, -1.0 to 1.4] events per 100 person-years; subdistribution hazard ratio, 1.01 [95% CI, 0.59-1.73]), or death (9.9 vs. 9.4 events per 100 person-years; incidence rate difference, 0.5 [95% CI, -1.6 to 2.6] events per 100 person-years; hazard ratio, 1.03 [95% CI, 0.77-1.38]).
Conclusions:
The authors report that compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with AF and severe CKD.
Perspective:
This observational study reports a 1.6 times risk of bleeding associated with 5 mg apixaban (vs. 2.5 mg) twice daily in patients with AF and non–dialysis-dependent CKD stage 4/5, with no differences in stroke/systemic embolism or death. Overall, these findings suggest that 2.5 mg apixaban may be a better choice than 5 mg for patients with AF and severe CKD, in line with the KDIGO Guidelines’ dosing for this population and dosing suggested by European Medicines Agency, which are different from those issued by the US Food and Drug Administration. Given several limitations of the current analysis, and the unclear benefits of anticoagulation in severe CKD and AF, prospective randomized controlled trials (RCTs) are required to provide guidance on the decision to initiate anticoagulation and which anticoagulant and what dose to use in this population at very high risk for death.
Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias
Keywords: Anticoagulants, Atrial Fibrillation, Embolism, Renal Insufficiency, Chronic, Stroke
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