Poor Correlation of Rivaroxaban Concentration with the Routine Coagulation Screening Test in Chinese Patients with Atrial Fibrillation

Table 3

Plasma concentration and coagulation parameters in patients after initiating rivaroxaban therapy.

Characteristic	Study population (n = 116)	Rivaroxaban alone (n = 10)	Amiodarone (n = 11)	Digoxin (n = 9)	Digoxin plus febuxostat (n = 3)	Febuxostat (n = 6)	Statin (n = 19)	Other medication with no major effect (n = 50)	Other medication with mixed effects (n = 4)	Benzbromarone	Glimepiride
Ctrough (ng/mL)	31.3 ± 45.4	24.8 ± 14.6	44.6 ± 69.9	24.5 ± 21.4	78.8 ± 50.4	30.3 ± 26.9	26.6 ± 34.7	21.2 ± 17.0	47.48 ± 48.12	40.3	204.6
Cpeak (ng/mL)	189.0 ± 133.2^###	186.6 ± 151.8	204.5 ± 89.8	170.6 ± 90.0	320.4 ± 235.1	195.1 ± 109.4	148.7 ± 156.9	170.2 ± 101.6	270.25 ± 157.89	327.5	533.5
Normalized Ctrough (ng/mL/mg)	1.68 ± 2.29	1.24 ± 0.73	2.23 ± 3.49	1.48 ± 1.32	4.56 ± 1.91	2.07 ± 1.81	1.38 ± 1.72	1.12 ± 0.87	2.37 ± 2.41	2.34	10.23
Normalized Cpeak (ng/mL/mg)	10.31 ± 7.31	9.33 ± 7.59	10.23 ± 4.49	9.57 ± 4.70	21.14 ± 14.37	13.92 ± 9.71	8.19 ± 8.41	9.17 ± 5.43	13.51 ± 7.89	17.91	26.68
PT (s)	12.93 ± 2.16	12.81 ± 1.44	12.89 ± 1.98	13.73 ± 1.89	18.47 ± 4.97	13.60 ± 2.06	12.87 ± 2.14	12.22 ± 1.38	14.85 ± 3.32	11.95	14.9
INR	1.11 ± 0.18	1.09 ± 0.12	1.11 ± 0.17	1.17 ± 0.15	1.57 ± 0.43	1.16 ± 0.17	1.11 ± 0.18	1.05 ± 0.12	1.27 ± 0.28	1.04	1.31
aPTT (s)	30.9 ± 5.1	31.9 ± 4.7	30.3 ± 4.5	30.6 ± 3.8	32.9 ± 4.1	31.0 ± 3.7	31.0 ± 4.2	30.1 ± 5.1	36.80 ± 9.63	26	36.6
TT (s)	18.52 ± 4.26	18.26 ± 1.89	17.79 ± 1.38	17.21 ± 1.79	18.40 ± 0.36	23.58 ± 15.72	18.15 ± 1.44	18.62 ± 3.33	17.43 ± 1.28	18.05	18.25

In this study, 1 received rivaroxaban and cimetidine (0.9%, dosage 20 mg, and CYP3A4 inhibition); 1 received rivaroxaban, celecoxib, and statin (0.9%, dosage 20 mg, CYP3A4, CYP2C9, P-gp, and BCRP competition); 1 received rivaroxaban, digoxin, and cimetidine (0.9%, dosage 20 mg, P-gp competition, and CYP3A4 inhibition); 1 received rivaroxaban and clarithromycin (0.9%, dosage 20 mg, and combined P-gp and CYP3A4 inhibition). Due to the mixed effect on drug metabolism enzyme and transporter, the plasma concentrations and coagulation parameters obtained from aforementioned patients were combined into one group (other medication with mixed effects). The details were summarized in Supplemental Table 6. PT, prothrombin time; aPTT, activated partial thromboplastin time; INR, international normalized ratio; TT, thrombin time; C_trough, trough concentration; C_peak, peak concentration. Normalized concentrations were used for dose and body weight correction, thus reducing variation. ,  < 0.05 when compared with the rivaroxaban alone group. ,  < 0.01 when compared with the rivaroxaban alone group. ^###,  < 0.001 when compared with C_trough. When patients were less than 3, statistic comparisons were not performed.