Clinical evaluation of laboratory methods to monitor apixaban treatment in patients with atrial fibrillation

- First “real-life” clinical apixaban study in a well-defined cohort of AF-patients.
- The functional assay apixaban anti-FXa activity reflects apixaban anticoagulation
- aPTT or PT-INR are not sensitive enough for clinical purposes.
- Direct measurement by LC-MS/MS is needed to quantify low concentrations of apixaban
- Compared to clinical trials, we observed relatively lower apixaban exposure

IntroductionThe direct factor-Xa inhibitor apixaban is approved e.g. for the prevention of stroke in patients with atrial fibrillation (AF). Although routine monitoring of apixaban therapy is currently not recommended, selective monitoring could be useful to optimize efficacy and safety in certain clinical situations. We studied the exposure and effect of apixaban using different laboratory methods in a clinical setting with a well-defined cohort of AF patients.Material and methodsSeventy AF patients (72 ± 7.4 years, 64 % men, mean CHADS2 score 1.7) treated with apixaban 2.5 (n = 10) or 5 mg BID (n = 60). Trough plasma apixaban concentrations determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to the coagulation assays Anti-factor Xa, PT-INR and aPTT.ResultsThe apixaban plasma concentration determined by LC-MS/MS varied more than 10-fold overall. The range was between 15-83 and 29-186 ng/mL for the 2.5 mg BID and 5 mg BID respectively, with patients receiving 5 mg BID having significantly higher apixaban concentrations (p < 0.001). A strong correlation between LC-MS/MS and anti-FXa-assay was found (p < 0.001), while aPTT and PT-INR were not sensitive enough. There were no significant correlations between gender, creatinine clearance, body weight or age and apixaban exposure.ConclusionsAnti-FXa-assay performed well upon apixaban concentrations in a normal exposure range. Still LC-MS/MS remains the “gold standard” method, covering also low concentrations. Compared to clinical trials, we observed relatively lower apixaban exposure and a more pronounced difference between high and low dose. Additional information regarding apixaban exposure and benefit-risk profile is needed in order to individualize treatment.