In atrial fibrillation patients on hemodialysis, labeled apixaban dosing was associated with significant overexposure (aOR 8.07; 95% CI 1.06-61.45), suggesting 2.5 mg twice daily is optimal.
Cohort (n=596)
Does apixaban dosing regimen affect drug overexposure and bleeding risk in patients with atrial fibrillation and end-stage renal disease or on hemodialysis?
In patients with CrCL <25 mL/min or on hemodialysis, a 2.5 mg twice daily apixaban regimen may be optimal to avoid the high probability of overexposure seen with the 5 mg regimen.
Effect estimate: aOR 8.07 (95% CI 1.06-61.45)
Abstract Background and aims This study aimed to investigate the distribution of apixaban concentrations in patients with end-stage renal disease, including those on hemodialysis (HD) and to evaluate the most appropriate dosing regimens. Methods We enrolled 596 patients with atrial fibrillation receiving apixaban therapy and measured their trough concentrations. The labeled dosing regimen was defined according to the prescribing information. For HD patients, it was defined as 2.5 mg twice daily (bid) regimen. Results In our cohort, patients with CrCL25 mL/min, but not those with HD had significantly higher apixaban concentrations. After adjustment, off-labeled overdosing was significantly associated with apixaban overexposure (aOR 4.55 1.43–14.44). Among patients receiving labeled dosing regimens (n=450, 75.5%), both CrCL25 mL/min (aOR 12.53 2.59, 60.63) and HD (aOR 8.07 1.06, 61.45) were associated with apixaban overexposure after adjustment. Model-based predictions showed that the probability of overexposure ranged from approximately 25% with the 2.5 mg bid regimen to 50% with the 5 mg bid regimen in patients with CrCL25 mL/min or those undergoing HD. During a median follow-up of 1.9 years, the incidence rates of major bleeding were 6.37, 2.85, and 2.11 per 100 person-years for the HD, CrCL25 mL/min, and CrCL 25 to 50 or ≥50 mL/min groups, respectively (log-rank test P=0.55). Conclusions In patients with CrCL 25 mL/min or on HD, a 2.5 mg twice daily apixaban regimen may be a more optimal therapeutic option due to a high probability of overexposure with the 5 mg regimen. Conflict of interest Sung-Chun Tang, Shin-Yi Lin, Chih-Hao Chen, Yen-Bin Liu, Li-Ting Ho, Ching-Hua Kuo, Yu-Fong Peng, Shu-Wen Lin and Jiann-Shing Jeng: nothing to disclose
Lin et al. (Fri,) conducted a cohort in Atrial fibrillation with end-stage renal disease or hemodialysis (n=596). Apixaban vs. Different renal function groups and dosing regimens was evaluated on Apixaban overexposure in hemodialysis patients on labeled dosing (aOR 8.07, 95% CI 1.06-61.45). In atrial fibrillation patients on hemodialysis, labeled apixaban dosing was associated with significant overexposure (aOR 8.07; 95% CI 1.06-61.45), suggesting 2.5 mg twice daily is optimal.