Peak and trough concentrations of apixaban and rivaroxaban in adult patients: a systematic review and meta-analysis

BACKGROUND: Apixaban and rivaroxaban are activated factor X (FXa) inhibitors commonly used for treatment of venous thromboembolism and stroke prevention in patients with atrial fibrillation. While routine monitoring of their concentrations is not recommended, but it may be beneficial in certain situations. Expected peak and trough concentrations remain poorly understood, with most data derived from small studies.

OBJECTIVES: To establish the average peak and trough concentrations of apixaban and rivaroxaban from real-world studies.

METHODS: PubMed, Scopus, and Web of Science were searched until October 2023 for observational studies reporting apixaban and rivaroxaban concentrations. Meta-regression was used to examine factors influencing these concentrations.

RESULTS: Sixteen studies involving 1054 apixaban and 1321 rivaroxaban patients were pooled using random-effects model. Mean apixaban peak concentrations were 157 ng/mL (95% CI, 127-187) for 2.5 mg and 228 ng/mL (95% CI, 204-252) for 5 mg, with trough concentrations of 77 ng/mL (95% CI, 56-98) and 113 ng/mL (95% CI, 101-124), respectively. Mean rivaroxaban peak concentrations were 168 ng/mL (95% CI, 104-232) for 10 mg, 225 ng/mL (95% CI, 192-257) for 15 mg, and 229 ng/mL (95% CI, 193-264) for 20 mg, with trough concentrations of 23 ng/mL (95% CI, 13-32), 31 ng/mL (95% CI, 26-36), and 36 ng/mL (95% CI, 25-47), respectively. Meta-regression revealed age and creatinine clearance correlated with apixaban peak concentrations. Creatinine clearance correlated with apixaban and rivaroxaban trough concentrations.

CONCLUSION: The pooled mean concentrations align with expected concentration ranges reported in different pharmacokinetic studies.