Variability and Clinical Characteristics of Anti-factor Xa Activity Treated with Rivaroxaban in Chinese Patients Aged ≥ 80 years: A Single-center Study

Introduction: Assessment of rivaroxaban concentrations is warranted in advanced age patients treated with rivaroxaban, which may instruct individual dose to reduce bleeding risk. Anti-Xa chromogenic assay has been demonstrated good correlation between rivaroxaban plasma concentration and anti-factor Xa activity (AXA) within the clinical therapeutic dose range. We aimed to assess the variability of AXA and explore clinical characteristics associated with AXA in patients over 80 years treated with rivaroxaban in daily practice. Method: This study subjects were patients over 80 years treated with rivaroxaban hospitalized in the Department of Gerontology of Peking University First Hospital from 2016 to 2021. The medical data were extracted from electronic records: baseline characteristics, and AXA including trough and peak at day 3 and day 30 after rivaroxaban therapy. Inter- individual variability was calculated by mean ± SD, max-min and coefficient of variation (CV), which was calculated by(SD/mean) x 100. Intra- individual variability was assessed by paired-samples T test. Spearman and Pearson correlation analysis were used to evaluate the correlation between AXA and PT, APTT, INR, and clinical characteristics. Result: A total of 145 Chinese patients over 80 years old taking rivaroxaban were included in this study, with an average age of 85.9 ± 4.2 years old, among which 101 were males (69.7%). There were 57 patients (39.3%) in rivaroxaban 5mg BID group and 88 patients (60.7%) in 2.5mg BID group. In terms of interindividual variation, the CV of AXA trough value in patients using rivaroxaban ranged from 58–77%, and the CV of AXA peak ranged from 48–53%. For intra-individual variability, there was no significant difference of the AXA between day 3 and day 30. Body weight was positively correlated with AXA peak of rivaroxaban 5mg BID group (r = 0.331, p = 0.019). ADL score was positively correlated with AXA trough (r = 0.264, p = 0.020) and AXA peak (r = 0.290, p = 0.010) in rivaroxaban 2.5 mg BID. In the rivaroxaban 2.5mg BID group, creatinine clearance was negatively correlated with AXA trough value (r = -0.400, p = 0.001), and also between AXA peak both in rivaroxaban 2.5 mg BID (r = -0.249, p = 0.029) and rivaroxaban 5 mg BID (r = -0.330, p = 0.018). There was a positive correlation present between PT peak and AXA peak, including rivaroxaban 5 mg BID (r = 0.308, p = 0.033) and rivaroxaban 2.5 mg BID (r = 0.430, p = 0.000), and between PT trough and AXA trough in rivaroxaban 5 mg BID (r = 0.406, p = 0.002). The correlation between APTT and AXA is not significant, except APTT peak and AXA peak in rivaroxaban 2.5 mg BID (r = 0.340, p = 0.000). Conclusion: In this study, in Chinese patients treated with rivaroxaban for more than 80 years, there was significant inter-individual variation in AXA, but not significant intra-individual variation. It is recommended to measure AXA trough and peak into the effective treatment range at the initiation of rivaroxaban treatment in patients over 80 years. Creatinine clearance was inversely correlated with AXA, suggesting an increased risk of bleeding with reduced renal function. There was a significant correlation present between PT and AXA, while the correlation between APTT and AXA was poor.