J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 8, Number 12, December 2016, pages 899-907

Evaluation of the Antithrombotic Effects of Rivaroxaban and Apixaban Using the Total Thrombus-Formation Analysis System^®: In Vitro and Ex Vivo Studies

Figure 1. In vitro antithrombotic effects (AR-AUC (a) and PL-AUC (b)) in the absence of (control) or presence of (spiked) rivaroxaban and apixaban in blood from healthy volunteers using AR-chips and PL-chips. *P < 0.05 vs. control.

Figure 2. Antithrombotic capacities (AR-AUC (a) and PL-AUC (b)) at trough and peak in blood from patients. †P < 0.05 vs. rivaroxaban at trough. *P < 0.05 vs. trough.

**Table 1.** Changes in T-TAS^® Parameters of *In Vitro* Experiments in the Rivaroxaban and Apixaban
	Rivaroxaban (n = 16)	Apixaban (n = 4)
Continuous variables are expressed as mean ± SD. *P < 0.05 vs. control.
AR-T₁₀ (min)	7.9 ± 2.2	16.1 ± 4.5*	6.7 ± 0.2	14.0 ± 1.3*
AR-T₈₀ (min)	12.4 ± 2.4	22.6 ± 3.2*	11.4 ± 1.1	22.6 ± 2.2*
PL-T₁₀ (min)	2.3 ± 0.7	2.9 ± 0.7	2.2 ± 1.1	2.8 ± 0.7
PL-T₆₀ (min)	6.0 ± 1.7	6.6 ± 1.3	6.2 ± 2.6	6.2 ± 1.5

Table 1. Changes in T-TAS^® Parameters of In Vitro Experiments in the Rivaroxaban and Apixaban

Rivaroxaban (n = 16)

Apixaban (n = 4)

Control

Spiked

Control

Spiked

Continuous variables are expressed as mean ± SD. *P < 0.05 vs. control.

AR-T₁₀ (min)

7.9 ± 2.2

16.1 ± 4.5*

6.7 ± 0.2

14.0 ± 1.3*

AR-T₈₀ (min)

12.4 ± 2.4

22.6 ± 3.2*

11.4 ± 1.1

22.6 ± 2.2*

PL-T₁₀ (min)

2.3 ± 0.7

2.9 ± 0.7

2.2 ± 1.1

2.8 ± 0.7

PL-T₆₀ (min)

6.0 ± 1.7

6.6 ± 1.3

6.2 ± 2.6

6.2 ± 1.5

**Table 2.** Patient Characteristics in All Patients, the Rivaroxaban and Apixaban Groups
	All	Rivaroxaban	Apixaban
Continuous variables are expressed as mean ± SD. IN/TN: incidence number/total number of subjects; BMI: body mass index; HTN: hypertension; DL: dyslipidemia; DM: diabetes mellitus; AF: atrial fibrillation; eGFR: estimated glomerular filtration rate; Ht: hematocrit; Plt: platelet counts; ARB/ACE-I: angiotensin II receptor blocker/angiotensin converting enzyme inhibitor. †P < 0.05 vs. rivaroxaban group.
N	16	6	10
Age, years	68 ± 9	67 ± 10	69 ± 9
Male, IN/TN (%)	10/16 (63)	5/6 (83)	5/10 (50)†
BMI, kg/m²	24 ± 3	24 ± 4	23 ± 4
HTN, IN/TN (%)	12/16 (75)	4/6 (67)	8/10 (80)
DL, IN/TN (%)	10/16 (63)	2/6 (33)	8/10 (80)†
DM, IN/TN (%)	4/16 (25)	1/6 (17)	3/10 (30)
eGFR, mL/min/1.73 m²	55.6 ± 11.6	56.4 ± 12.7	52.1 ± 10.0
Ht, %	39.6 ± 3.3	39.5 ± 2.7	39.7 ± 3.8
Plt, 10⁴/μL	19.7 ± 6.1	21.7 ± 6.1	17.2 ± 3.7
Medication
ARB/ACE-I, IN/TN (%)	11/16 (69)	4/6 (67)	7/10 (70)
Beta blocker, IN/TN (%)	7/16 (44)	3/6 (50)	4/10 (40)
Diuretic, IN/TN (%)	4/16 (25)	2/6 (33)	2/10 (20)
Statin, IN/TN (%)	9/16 (56)	2/6 (33)	7/10 (70)

Table 2. Patient Characteristics in All Patients, the Rivaroxaban and Apixaban Groups

All

Rivaroxaban

Apixaban

Continuous variables are expressed as mean ± SD. IN/TN: incidence number/total number of subjects; BMI: body mass index; HTN: hypertension; DL: dyslipidemia; DM: diabetes mellitus; AF: atrial fibrillation; eGFR: estimated glomerular filtration rate; Ht: hematocrit; Plt: platelet counts; ARB/ACE-I: angiotensin II receptor blocker/angiotensin converting enzyme inhibitor. †P < 0.05 vs. rivaroxaban group.

Age, years

68 ± 9

67 ± 10

69 ± 9

Male, IN/TN (%)

10/16 (63)

5/6 (83)

5/10 (50)†

BMI, kg/m²

24 ± 3

24 ± 4

23 ± 4

HTN, IN/TN (%)

12/16 (75)

4/6 (67)

8/10 (80)

DL, IN/TN (%)

10/16 (63)

2/6 (33)

8/10 (80)†

DM, IN/TN (%)

4/16 (25)

1/6 (17)

3/10 (30)

eGFR, mL/min/1.73 m²

55.6 ± 11.6

56.4 ± 12.7

52.1 ± 10.0

Ht, %

39.6 ± 3.3

39.5 ± 2.7

39.7 ± 3.8

Plt, 10⁴/μL

19.7 ± 6.1

21.7 ± 6.1

17.2 ± 3.7

Medication

ARB/ACE-I, IN/TN (%)

11/16 (69)

4/6 (67)

7/10 (70)

Beta blocker, IN/TN (%)

7/16 (44)

3/6 (50)

4/10 (40)

Diuretic, IN/TN (%)

4/16 (25)

2/6 (33)

2/10 (20)

Statin, IN/TN (%)

9/16 (56)

2/6 (33)

7/10 (70)

**Table 3.** Changes in T-TAS^® Parameters, PT-INR and APTT at Trough and Peak in Blood in the Rivaroxaban and Apixaban Groups
	Rivaroxaban (n = 6)	Apixaban (n = 10)
Continuous variables are expressed as mean ± SD. *P < 0.05 vs. trough, †P < 0.05 vs. rivaroxaban group.
AR-T₁₀ (min)	9.2 ± 2.9	12.3 ± 2.3	11.9 ± 2.5	15.5 ± 3.2*
AR-T₈₀ (min)	13.7 ± 3.2	18.3 ± 3.5*	18.3 ± 3.1†	22.0 ± 3.3*
PL-T₁₀(min)	2.4 ± 0.7	2.4 ± 1.5	2.9 ± 1.3	3.5 ± 1.0
PL-T₆₀ (min)	6.7 ± 1.3	6.2 ± 0.8	8.3 ± 0.8	8.0 ± 0.3
PT-INR	1.2 ± 0.2	1.3 ± 0.2	1.1 ± 0.1	1.2 ± 0.1
APTT (s)	34.4 ± 5.3	40.7 ± 14.3	31.4 ± 2.3	31.9 ± 2.8

Table 3. Changes in T-TAS^® Parameters, PT-INR and APTT at Trough and Peak in Blood in the Rivaroxaban and Apixaban Groups

Rivaroxaban (n = 6)

Apixaban (n = 10)

Trough

Peak

Trough

Peak

Continuous variables are expressed as mean ± SD. *P < 0.05 vs. trough, †P < 0.05 vs. rivaroxaban group.

AR-T₁₀ (min)

9.2 ± 2.9

12.3 ± 2.3

11.9 ± 2.5

15.5 ± 3.2*

AR-T₈₀ (min)

13.7 ± 3.2

18.3 ± 3.5*

18.3 ± 3.1†

22.0 ± 3.3*

PL-T₁₀(min)

2.4 ± 0.7

2.4 ± 1.5

2.9 ± 1.3

3.5 ± 1.0

PL-T₆₀ (min)

6.7 ± 1.3

6.2 ± 0.8

8.3 ± 0.8

8.0 ± 0.3

PT-INR

1.2 ± 0.2

1.3 ± 0.2

1.1 ± 0.1

1.2 ± 0.1

APTT (s)

34.4 ± 5.3

40.7 ± 14.3

31.4 ± 2.3

31.9 ± 2.8