Gender-Associated Variation in DOAC Levels

Background: Direct oral anticoagulants (DOAC) such as Xa inhibitors rivaroxaban (riva) and apixaban (apix) are increasingly replacing Vitamin K antagonists in prophylaxis and treatment of venous thromboembolism (VTE). Measurements of DOAC plasma levels may be necessary in certain clinical conditions to determine the further dosage. Making decisions is made more difficult by the fact that the peak and trough plasma levels are subject to strong inter-individual fluctuations with overlapping reference ranges. We wanted to find out whether the peak and trough levels can be narrowed if they are determined based on age and gender. Methods: Therefore, we collected data on peak and trough anti-Xa concentrations in patients treated with either rivaroxaban (n = 93) or apixaban (n = 51) in one center. After exclusion of blood samples of uncertain oral intake, 83 samples for rivaroxaban and 49 samples for apixaban remained for further analysis. Differences between male (riva n = 42, apix n = 28) and female (riva n = 41 and apix n = 21) as well as young (<= 60 years, riva n = 44, apix n = 23) and elder (> 60 years) patients (riva n = 39 and apix n = 26) were analyzed by Student`s t-test and retrospective regression. Results: We found no differences in age and gender for the apix peak levels. But women had significantly higher riva peak concentrations than men (308.8 +/- 178.1 ng/mL versus 206.4 +/- 80 ng/mL, p = 0.013). Patients older than 60 years had significantly higher riva peak levels than those younger than 60 (293.7 +/- 126.7 ng/mL versus 211.7 +/- 158.4 ng/mL, p = 1.29 x 10(-8)). Conclusions: In search of narrowing standard peak and trough levels in patients' sera we found significant differences between patients below and above sixty years of age. Gender-associated differences were found in rivaroxaban levels possibly explaining DOAC associated hypermenorrhea. In conclusion, gender and age should be included in the determination of peak blood concentration references.