Abstract T P346: Anticoagulation Intensity of Low-dose Rivaroxaban for Japanese Patients With Nonvalvular Atrial Fibrillation

Abstract

Objective: In Japan, low-dose rivaroxaban [15 mg o.d. and 10 mg o.d. only for CCr 30-49 mL/min] was approved for clinical use to NVAF patients, because of its unique pharmacokinetics in Japanese subjects showing higher rivaroxaban concentration than Caucasian subjects when using the same dosage and the results of the J-ROCKET AF trial (Hori M, et al: Circ J 2012). We aimed to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese NVAF patients, especially in those taking crushed tablets. Methods: Consecutive stroke patients with NVAF admitted between July 2012 and July 2013 were studied. Prothrombin time (PT, Recombiplastin/HemosIL®), activated partial thromboplastin time (aPTT, Actin/Sysmex®), and anti-Xa chromogenic assay (Stago®) were measured just before and 4h and 9 h after the administration at the steady state of rivaroxaban (mean 6th day). We calibrated its plasma concentration based on anti-Xa assay. Results: Of 104 patients (32 women, 74±9 y.o., BW 59±11 kg) involving 36 with CCr <50 ml/min (Cockcroft-Gault), 57 took 15 mg o.d. of rivaroxaban and 46 took 10 mg o.d. Median PT, aPTT, and concentration were 12.8s, 31s, and 13.5 ng/ml just before administration, 19.3s, 42s, and 170.5 ng/ml at 4h, and 15.8s, 37s, and 63.0 ng/ml at 9h. Both PT and aPTT were positively correlated with concentration (r=0.88, 0.74, respectively). Age, BW, CCr, and rivaroxaban dosage were not associated with concentrations at 4h and 9h, though they were associated with concentration just before administration. In 10 patients taking crushed tablets, including 5 patients via a nasogastric tube, median PT (15.8s vs. 19.7s, p<0.001), aPTT (33s vs. 42s, p=0.012) and concentration (53 ng/ml vs. 186 ng/ml, p<0.001) at 4h were lower than the remaining 94 patients. Crushed tablets were independently associated with lower anticoagulant intensity. Conclusion: Nearly peak concentration of rivaroxaban was similar or a little lower than that in the ROCKET AF and J-ROCKET AF trials (Kaneko M, et al: Drug Metab Pharmacokinet 2013). Tablet crushing may decrease anticoagulation intensity.