Serum Concentration of Apixaban in Relation to Renal Function in Older Hospitalized Patients.

Abstract

Background and objective: Apixaban is the most prescribed direct-acting oral anticoagulant drug. According to its product information, clearance is only partially renal. However, little is known about the impact of renal function on apixaban pharmacokinetics in real-world settings. The aim of this study was therefore to investigate serum concentrations of apixaban in relation to renal function in acutely hospitalised, older patients.

Methods: The study was conducted with a prospective, observational design. Apixaban-treated patients ≥ 65 years acutely admitted to Haukeland University Hospital in Bergen, Norway, during a four-month period were included. Serum concentrations of apixaban were measured at hospitalization and assessed in relation to glomerular filtration rate (GFR). Spearman rank test was used to investigate correlation between GFR and dose-adjusted serum concentrations of apixaban. In addition, dose-adjusted serum concentrations were compared between GFR subgroups by Mann-Whitney tests.

Results: In total, 36 patients were included (median age 84.5 years, range 68-96 years). Median GFR at admission was 43 ml/min (range 17-119 ml/min). Dose-adjusted apixaban serum concentrations correlated significantly with GFR (Spearman r = - 0.54, p = 0.0008). Compared with patients with GFR > 90 ml/min, apixaban dose-adjusted serum concentrations were 3.3-fold, 1.8-fold and 2.0-fold higher in patients with GFR < 30 ml/min (p = 0.01), 30-59 ml/min (p = 0.04) and 60-89 ml/min (n.s.), respectively.

Conclusions: The study shows that dose-adjusted serum concentration of apixaban significantly correlates with renal function in older, acute hospitalized patients. These real-life data indicate that apixaban-treated patients with GFR < 30 ml/min may require around 70% lower dose than normal to achieve sufficient antithrombotic effect and prevent risk of bleedings.