Plasma apixaban concentrations and thrombin generation assay parameters in response to dose reduction for atrial fibrillation

作者：Muhan Yeo, So‐Ryoung Lee, Eue‐Keun Choi, JungMin Choi, Kyung‐Yeon Lee, Hyo‐Jeong Ahn, Soonil Kwon, Hyoung‐Seob Park, Hyun Kyung Kim, Seil Oh, Gregory Y. H. Lip · 发表于：British Journal of Clinical Pharmacology · 年份：2024 · DOI：10.1111/bcp.16211 · 被引用次数：6 · 研究领域：Atrial Fibrillation Management and Outcomes、Antiplatelet Therapy and Cardiovascular Diseases、Pharmacovigilance and Adverse Drug Reactions

AIMS: To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban. METHODS: This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels. RESULTS: The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations. CONCLUSION: Off-label underdosed apixaban resulted in lower apixaban concentrations than bot...