Canadian Journal of Cardiology
Abstract| Volume 31, ISSUE 10, SUPPLEMENT , S103, October 2015



      Atrial fibrillation (AF) is the most common cardiac arrhythmia, especially in the elderly. With our aging population there is a growing need of oral anticoagulants (OACs) for stroke prevention in AF patients. Factor Xa Inhibitors (FXaI), Rivaroxaban and Apixaban are widely used for OAC therapy. Outside of clinical trials, the interpatient variation in drug response has not been assessed. The objectives of this study are to examine interpatient variability of plasma Rivaroxaban and Apixaban concentrations, and to better identify patients at risk for extremes in drug concentration leading to serious adverse events (stroke or bleeding).


      In this prospective cohort study, we enrolled AF patients prescribed Rivaroxaban or Apixaban followed either by the oral anticoagulation clinic or cardiology clinic. A single blood sample from each patient during their regular dosing cycle, and the timing of their last dose were collected. FXaI plasma concentrations were determined using liquid chromatography-tandem mass spectrometry, these values were referenced in comparison to those currently reported in literature.


      To date, 70 AF patients, all taking FXaIs were included (Rivaroxaban N=43, and Apixaban N=27). Mean age was 73.2±10.5, 52% were female. There was a wide variation of FXaI concentrations. Rivaroxaban plasma samples collected within 4-8 hours and 9-24 hours of the last dose ranged from 39.7 to 632 ng/ml (16-fold variation) and 10.9 to 316 ng/ml (29-fold variation), respectively. Twenty-one percent of the Rivaroxaban cohort attained a level greater than their predicted 95th percentile. Apixaban plasma concentrations ranged from 88.5 to 308 ng/ml (3.5-fold variation) and 61 to 443 ng/ml (7-fold variation) for samples collected within 3-5 hours and 5-12 hours of the last dose, respectively.


      There is great variation in observed Rivaroxaban and Apixaban plasma levels in our population, with a significant proportion of patients attaining higher than predicted plasma level. Therapeutic monitoring of these drugs may prove to be an important strategy for direct-acting OAC selection and dosing. Our findings may have major clinical relevance to safe and effective utilization of FXaI OACs.