ABSTRACT NUMBER: ESOC2026A690 REAL-WORLD APIXABAN CONCENTRATIONS IN END-STAGE RENAL DISEASE AND HEMODIALYSIS

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 CrCL<25 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 CrCL<25 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 CrCL<25 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, CrCL<25 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