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Plasma apixaban levels in Chinese patients with chronic kidney disease-Relationship with renal function and bleeding
Chun-Fung Sin1, Ka-Ping Wong1,1, Tsz-Fu Wong1
1Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Insights
Higher apixaban levels in patients with chronic kidney disease (CKD) correlate with worsening renal function and increased bleeding risk. Monitoring drug levels may help optimize dosage and reduce complications in CKD patients.
Area of Science:
- Pharmacology
- Nephrology
- Clinical Pharmacy
Background:
- Apixaban accumulation in plasma is a concern for patients with chronic kidney disease (CKD).
- Limited studies investigate apixaban levels and clinical events in CKD patients.
- Understanding drug pharmacokinetics in CKD is crucial for patient safety.
Purpose of the Study:
- To measure plasma apixaban levels in CKD patients (Stages 1-4).
- To correlate apixaban levels with renal function (eGFR) and clinical events.
- To assess the association between apixaban levels and bleeding complications.
Main Methods:
- Recruited 141 CKD patients on apixaban (2.5mg or 5mg BD).
- Measured peak (2h) and trough (12h) plasma apixaban levels.
- Correlated levels with estimated glomerular filtration rate (eGFR), prothrombin time (PT), and clinical events.
Main Results:
- Plasma apixaban levels (peak and trough) were significantly higher in CKD Stage 3 vs. Stages 1 & 2 (p < 0.05).
- Trough apixaban levels negatively correlated with eGFR (r² = -0.174 for 5mg, r² = -0.215 for 2.5mg).
- Higher trough apixaban levels were associated with increased risk of bleeding complications (OR: 1.011, p = 0.023).
Conclusions:
- Apixaban plasma levels increase with declining renal function in CKD patients.
- Elevated apixaban levels suggest a higher risk of bleeding complications.
- Further research is needed to evaluate drug monitoring for dose optimization and bleeding risk reduction.
Abstract:
Introduction: Accumulation of apixaban in plasma is a major concern in patients with chronic kidney disease (CKD). Studies that investigated plasma apixaban level in CKD patients and its association with clinically significant events are scarce. Methods: Patients with CKD Stage 1-4 who were taking apixaban, either 2.5 mg BD or 5 mg BD were recruited. The peak and trough plasma apixaban level were measured after 2 h and 12 h of last dose respectively. The results were correlated with renal function and clinical events during the period of follow-up from 1 January 2018 to 31 October 2021. Results: 141 patients (CKD Stage 1, n = 12; Stage 2, n = 74; Stage 3, n = 48, stage 4, n = 7) were included for analysis. The plasma peak and trough apixaban were significantly higher in patients with CKD stage 3 when compared with those having CKD stage 2 and 1 (peak levels: 223.4 ± 107.8 ng/ml vs. 161.0 ± 55.2 ng/ml vs. 126.6 ± 30.2 ng/ml; trough levels: 118.3 ± 67.9 ng/ml vs. 81.2 ± 33.0 ng/ml vs. 51.9 ± 31.1 ng/ml, p < 0.05 or all) in patients taking 5 mg BD. Plasma trough apixaban level was negatively correlated with eGFR in patients taking 5 mg BD (r 2 = -0.174, p < 0.001) and 2.5 mg BD (r 2 = -0.215, p < 0.05). The plasma peak and trough apixaban level correlated with PT (r 2 = 0.065, p = 0.003 and r 2 = 0.096, p < 0.01 respectively). Multivariate analysis showed that plasma trough apixaban levels were associated with the risk of bleeding complications (Odd ratio: 1.011, 95% CI:1.002-1.021, p = 0.023). Conclusion: The plasma apixaban level shows a trend of increase with worsening renal function, and an increase in the plasma apixaban level is suggestive of an increased risk of bleeding complications in patients with CKD. Further large-scale prospective studies are needed to evaluate relationship between plasma apixaban level and renal function as well as safety outcome in CKD patients. Moreover, the role of drug level monitoring should be prospectively evaluated for dosage optimization and the minimization of bleeding risks in CKD patients.
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