Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in patients undergoing cardiac catheterization.

Abstract

Patients treated with direct oral anticoagulants (DOACs) frequently undergo interventional procedures requiring temporary discontinuation of anticoagulant therapy. Little is known about remaining peri-procedural exposure to rivaroxaban in real-world patients. Fifty-six patients with rivaroxaban treatment and scheduled cardiac catheterization were included in this prospective, observational, and single-center study. Rivaroxaban concentrations were determined by LC-MS/MS and a chromogenic anti-Xa assay. Population pharmacokinetic modeling was carried out on LC-MS/MS concentration data using NONMEM software, and results were applied to Monte Carlo simulations to predict appropriate rivaroxaban discontinuation intervals. Rivaroxaban concentrations ranged from <LLOQ to 300.6ng/ml at the time of admission to hospital and from <LLOQ to 55.5ng/ml at the beginning of the procedure. Times since last rivaroxaban intake were (mean ± SD) 51.0 ± 31.7h (admission) and 85.5 ± 36.8h (start catheterization). LC-MS/MS and anti-Xa assay results were in good agreement (r = 0.958); however, the anti-Xa assay may underestimate low rivaroxaban concentrations and overestimate rivaroxaban exposure when performed on plasma samples contaminated with heparins. Pharmacokinetics of rivaroxaban were adequately described, and simulations predicted that 95% of patients will have rivaroxaban concentrations ≤ 28.4ng/ml (15mg dose group) and ≤ 31.9ng/ml (20mg dose group) after 48h of discontinuation. In the majority of patients, rivaroxaban plasma concentrations dropped below 30ng/ml after 48h of treatment discontinuation which is considered hemostatically safe before surgery with high bleeding risk. For accurate determination of low rivaroxaban concentrations, LC-MS/MS is the preferred choice.