Kreutz R, et al. – This randomized crossover study compared directly the steady–state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in nonvalvular atrial fibrillation. In comparison to apixaban 5 mg twice daily, rivaroxaban 20 mg once daily resulted in greater and more sustained inhibition of thrombin generation, despite similar exposure to both drug.

Methods

• Experts involved twenty-four healthy Caucasian male volunteers in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32).
• They randomized volunteers to receive rivaroxaban 20 mg once daily or apixaban 5 mg twice daily for 7 days followed by a washout period of at least 7 days before receiving the other treatment.
• At steady state and after drug discontinuation, plasma concentrations and anticoagulant effects were measured.

Results

• For both drugs, overall exposure was similar: the geometric mean area under the plasma concentration–time curve for the 0–24 h interval was 1830 μg h L-1 for rivaroxaban and 1860 μg h L-1for apixaban.
• As compared to apixaban, rivaroxaban was associated with a greater inhibition of endogenous thrombin potential (geometric mean area under the curve relative to baseline during the 0–24 h interval 15.5 vs 17.5) and a more pronounced maximal prolongation relative to baseline of prothrombin time (PT; 1.66-fold vs 1.14-fold) and activated partial thromboplastin time (aPTT; 1.43-fold vs 1.16-fold) at steady state.