Real-World Evaluation of the Safety and Effectiveness of Apixaban & Rivaroxaban Lead-in Dosing Compared to Parenteral Lead-in Dosing in the Treatment of Venous Thromboembolism: A Multi-Center Retrospective Cohort Study

Figures & data

Table 1 Patients’ Demographics and Clinical Characteristics

Patient Characteristics	Overall(n=389)	Lead-in Group		p-value
		Parenteral (n=93)	DOAC(n=296)
Age in years, mean (SD)	54.5 (20.1)	60.5 (20.3)	52.6 (19.7)	<0.001
BMI (kg/m^2), mean (SD)	30.9 (7.0)	30.2 (7.4)	31.1 (6.9)	0.306
Hospital Length of Stay (days)	7.1 (15.8)	15.2 (28.1)	4.6 (7.4)	<0.001
Gender				0.009
Male	148 (38.0)	46 (49.5)	102 (34.5)
Female	241 (62.0)	47 (50.5)	194 (65.5)
Pre-existing conditions
Atrial Fibrillation	8 (2.1)	3 (3.2)	5 (1.7)	0.403
Coronary Artery Disease	29 (7.5)	16 (17.2)	13 (4.4)	<0.001
Hypertension	149 (38.3)	45 (48.4)	104 (35.1)	0.022
Valvular Disease	3 (0.8)	1 (1.1)	2 (0.7)	0.560
Stroke	44 (11.3)	16 (17.2)	28 (9.5)	0.040
Transient Ischemic Attack	7 (1.8)	4 (4.3)	3 (1.0)	0.059
Diabetes Mellitus	138 (35.5)	41 (44.1)	97 (32.8)	0.047
Chronic Kidney Disease	21 (5.4)	6 (6.5)	15 (5.1)	0.606
Active Smoking	27 (6.9)	4 (4.3)	23 (7.8)	0.418
Active Cancer	16 (4.1)	9 (9.7)	7 (2.4)	0.002
On chemotherapy (among patients with cancer)	7 (43.8)	4 (44.4)	3 (42.9)	1.000
Thrombophilia	14 (3.6)	4 (4.3)	10 (3.4)	0.752
History of MB (within 12 months)	17 (4.4)	3 (3.2)	14 (4.7)	0.576
History of CRNMB (within 12 months)	12 (3.1)	2 (2.2)	10 (3.4)	0.737
History of any bleeding (within 12 months)	8 (2.1)	2 (2.2)	6 (2.0)	1.000
Concomitant medications
Aspirin	79 (20.3)	34 (36.6)	45 (15.2)	<0.001
P2Y12 Inhibitors				0.002
Clopidogrel	17 (4.4)	10 (10.8)	7 (2.4)
Ticagrelor	2 (0.5)	1 (1.1)	1 (0.3)
Risk Factors for VTE Recurrence
History of Previous VTE	43 (11.1)	8 (8.6)	35 (11.8)	0.382
Type of Historical VTE				0.563
DVT	33 (76.7)	6 (75.0)	27 (77.1)	0.338
Proximal DVT	2 (6.1)	1 (16.7)	1 (3.7)
Distal DVT	2 (6.1)	1 (16.7)	1 (3.7)
Mixed DVT	2 (6.1)	0 (0.0)	2 (7.4)
Unspecified DVT	27 (81.8)	4 (66.7)	23 (85.2)
PE	7 (16.3)	2 (25.0)	5 (14.3)	0.571
Segmental PE	1 (14.3)	0 (0.0)	1 (20.0)
Subsegmental PE	1 (14.3)	0 (0.0)	1 (20.0)
Unspecified PE	5 (71.4)	2 (100)	3 (60.0)
DVT plus PE	3 (7.0)	0 (0.0)	3 (8.6)
Time of Historical VTE				0.005
Within 3 months	3 (7.0)	0 (0.0)	3 (8.6)
Within 6 months	1 (2.3)	1 (12.5)	0 (0.0)
Within 12 months	2 (4.7)	0 (0.0)	2 (5.7)
Within >12 months	33 (76.7)	4 (50.0)	29 (82.9)
Use of oral contraceptives or ERT	44 (11.3)	6 (6.5)	38 (12.8)	0.104
Obesity (BMI >30 kg/m2)	201 (51.7)	51 (54.8)	150 (50.7)	0.490
Immobility	98 (25.2)	33 (35.5)	65 (22.0)	0.010
Major General Surgery (within one year)	37 (9.5)	7 (7.5)	30 (10.1)	0.398
Orthopedic Surgery (within one year)	34 (8.7)	13 (14.0)	21 (7.1)	0.058

Notes: Results are presented as frequency (percentage) unless otherwise indicated. p-values are from the t-test for continuous data and chi-square or fisher-exact test for categorical data.

Abbreviations: BMI, body mass index; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; ERT, estrogen replacement therapy; MB, major bleeding; CRNMB, clinically relevant non-major bleeding; SD, standard deviation.

Figure 1 Patients inclusion and exclusion flow diagram.

Table 2 Type of Current VTE Events and the Risk of Bleeding

VTE Characteristics	Overall(n=389)	Lead-in Group		p-value
		Parenteral (n=93)	DOAC(n=296)
Type of the current VTE event				0.060
DVT	173 (44.5)	32 (34.4)	141 (47.6)	0.132
Proximal DVT	119 (68.8)	18 (56.3)	101 (71.6)
Distal DVT	16 (9.2)	2 (6.3)	14 (9.9)
Mixed DVT	28 (16.2)	9 (28.1)	19 (13.5)
Unspecified DVT	10 (5.8)	3 (9.4)	7 (5.0)
PE	189 (48.6)	55 (59.1)	134 (45.3)	0.061
Segmental PE	81 (42.9)	29 (52.7)	52 (38.8)
Subsegmental PE	25 (13.2)	2 (3.6)	23 (17.2)
Mixed PE	55 (29.1)	15 (27.3)	40 (29.9)
Unspecified PE	28 (14.8)	9 (16.4)	19 (14.2)
DVT plus PE	27 (6.9)	6 (6.5)	21 (7.1)
DVT type of the DVT plus PE				0.287
Proximal DVT	14 (51.9)	5 (83.3)	9 (42.9)
Distal DVT	5 (18.5)	0 (0.0)	5 (23.8)
Mixed DVT	5 (18.5)	1 (16.7)	4 (19.0)
Unspecified DVT	3 (11.1)	0 (0.0)	3 (14.3)
PE type of the DVT plus PE				0.216
Segmental PE	11 (40.7)	3 (50.0)	8 (38.1)
Subsegmental PE	1 (3.7)	0 (0.0)	1 (4.8)
Mixed PE	8 (29.6)	0 (0.0)	8 (38.1)
Unspecified PE	7 (25.9)	3 (50.0)	4 (19.0)
VTE Etiology				0.323
Provoked	226 (58.1)	60 (64.5)	166 (56.1)
Unprovoked	80 (20.6)	15 (16.1)	65 (22.0)
Not reported	83 (21.3)	18 (19.4)	65 (22.0)
Bleeding Risk*				0.061
High risk	14 (3.6)	7 (7.5)	7 (2.4)
Intermediate risk	298 (76.6)	67 (72.0)	231 (78.0)
Low risk	77 (19.8)	19 (20.4)	58 (19.6)

Notes: Results are presented as frequency (percentage). *From the bleeding risk assessment score.

Abbreviations: VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; SD, standard deviation; BMI, body mass index.

Table 3 DOAC vs Parenteral Lead-in Dosing for VTE Treatment

Anticoagulation Characteristics	Overall	Apixaban	Rivaroxaban
Patients, N	389	202	187
DOAC lead-in dosing	296 (76.1)	149 (50.3)	147 (49.7)
Type of parenteral anticoagulant used (for less than 2 days), n (%)
LMWH	168 (56.8)	68 (45.6)	100 (68.0)
UFH	29 (9.8)	22 (14.8)	7 (4.8)
Fondaparinux	1 (0.3)	1 (0.7)	0 (0.00)
None	98 (33.1)	58 (38.9)	40 (27.2)
Duration for received lead-in dose of DOAC in days, Mean (SD)		7.0 (0.0)	21 (0.0)
Duration for received parenteral anticoagulant in days, Mean (SD)		1.3 (0.4)	1.2 (0.4)
Parenteral lead-in Dosing	93 (23.9)	53 (57.0)	40 (43.0)
Type of parenteral anticoagulant used, n (%)
LMWH	67 (72.0)	32 (60.4)	35 (87.5)
UFH	24 (25.8)	20 (37.7)	4 (10.0)
Fondaparinux	2 (2.2)	1 (1.9)	1 (2.5)
Duration for the lead-in parenteral anticoagulant in days, Mean (SD)		3.7 (2.4)	11.1 (5.8)

Note: Results are presented as frequency (percentage) unless otherwise indicated.

Abbreviations: VTE, venous thromboembolism; DOAC, direct oral anticoagulant; LMWH, low molecular weight heparin; UFH, unfractionated heparin; SD, standard deviation; IQR, interquartile range.

Table 4 Outcomes During Hospitalization and Up to 90 Days of the VTE Event

Outcome	Lead-in Group		p-value
	Parenteral	DOAC
Patients, N	93	296
rVTE Event
During Hospitalization	3 (3.3)	2 (0.6)	0.091
Within 30 days*	1 (1.1)	2 (0.7)	0.560
Within 90 days**	2 (2.2)	2 (0.7)	0.243
Total number of patients with rVTE within 90 days***	5 (5.4)	4 (1.4)	0.039
MB Event
During Hospitalization	13 (14.0)	11 (3.7)	<0.001
Within 30 days*	0 (0.0)	4 (1.4)	0.576
Within 90 days**	2 (2.2)	5 (1.7)	0.674
Total number of patients with MB within 90 days***	13 (14.0)	14 (4.7)	0.004
CRNMB Event
During Hospitalization	10 (10.8)	9 (3.0)	0.006
Within 30 days*	7 (7.5)	23 (7.8)	0.938
Within 90 days**	7 (7.5)	23 (7.8)	0.938
Total number of patients with CRNMB within 90 days***	15 (16.1)	29 (9.8)	0.092
Rehospitalization****
Within 30 days*	1 (1.1)	7 (2.4)	0.686
Within 90 days**	2 (2.2)	13 (4.4)	0.537
Death during hospitalization	2 (2.2)	0 (0.0)	0.032

Notes: Results are presented as frequency (percentage). p-values are from the chi-square or fisher-exact test. *Within 30 days: 30 days of the indexed event date (excluding hospitalization days). **Within 90 days: 90 days of the indexed event date (excluding hospitalization days). ***The Cumulative number of patients with the outcome within 90 days, including events occurring during the index hospitalization. ****Rehospitalization due to VTE-related causes (recurrence, deterioration, or bleeding). Two patients in the recommended group and two in the parenteral lead-in group had two MB events each, and three patients from the recommended group and two patients in the parenteral lead-in group had two CRNMB events each during the 90 days of follow-up after the indexed VTE event, including events that occurred during the index hospitalization.

Abbreviations: rVTE, recurrent venous thromboembolism; VTE, venous thromboembolism; MB, major bleeding; CRNMB, clinically relevant non-major bleeding.