Comparative Bleeding Risk of Brand Vs Generic Rivaroxaban in Elderly Inpatients with Atrial Fibrillation

Figures & data

Video Abstract

© 2024 Chen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

Figure 1 The flow diagram of study.

Table 1 Demographics and Clinical Characteristics in Patients Treated with Brand and Generic Rivaroxaban

Variables	Total (n=1008)	Brand Group (n=626)	Generic Group (n=382)	ASD
Personal characteristics
Gender (female) n(%)	456 (45.2)	283 (45.2)	173 (45.3)	0.002
Age, years, (median [IQR])	79.00 [73.00, 85.00]	79.00 [74.00, 85.00]	79.00 [73.00, 85.00]	0.09
Weight, kg, (median [IQR])	60.00 [51.00, 70.00]	60.00 [52.00, 70.00]	61.00 [51.00, 69.00]	0.023
BMI, kg/m^2 (median [IQR])	22.99 [20.42, 25.71]	22.89 [20.28, 25.71]	23.18 [20.76, 25.78]	0.038
Educational_level^a (high) n(%)	128 (12.7)	85 (13.6)	43 (11.3)	0.07
Systolic_pressure (median [IQR])	139.00 [126.00, 156.00]	139.00 [126.00, 156.00]	139.00 [127.00, 154.00]	0.024
Current_tobacco_use (yes) n(%)	114 (11.3)	81 (12.9)	33 (8.6)	0.139
Current_alcohol_use (yes) n(%)	99 (9.8)	67 (10.7)	32 (8.4)	0.079
History_of_digestive_diseases (yes) n(%)	182 (18.1)	115 (18.4)	67 (17.5)	0.022
Bleeding_history (yes) n(%)	43 (4.3)	26 (4.2)	17 (4.5)	0.015
Thrombotic_history (yes) n(%)	317 (31.4)	219 (35.0)	98 (25.7)	0.204
CHA2DS2VASc (≥3) n(%)	842 (83.5)	534 (85.3)	308 (80.6)	0.168
HAS_BLED (≥3) n(%)	221 (21.9)	144 (23.0)	77 (20.2)	0.058
Comorbid conditions
Hypertension (yes) n(%)	702 (69.6)	442 (70.6)	260 (68.1)	0.055
Diabetes (yes) n(%)	243 (24.1)	151 (24.1)	92 (24.1)	0.001
Cancer (yes) n(%)	87 (8.6)	48 (7.7)	39 (10.2)	0.089
Heart_failure (yes) n(%)	383 (38.0)	254 (40.6)	129 (33.8)	0.141
Coronary_heart_disease (yes) n(%)	398 (39.5)	266 (42.5)	132 (34.6)	0.164
Hyperthyroidism (yes) n(%)	14 (1.4)	6 (1.0)	8 (2.1)	0.093
Hypothyroidism (yes) n(%)	52 (5.2)	38 (6.1)	14 (3.7)	0.112
Vascular_disease (yes) n(%)	246 (24.4)	138 (22.0)	108 (28.3)	0.144
Laboratory tests (median [IQR])
Total_bilirubin, μmol/L	14.80 [11.40, 20.25]	14.40 [11.30, 19.50]	15.45 [11.43, 20.80]	0.039
Albumin, g/L	36.00 [33.10, 39.00]	35.90 [33.30, 39.20]	36.00 [33.10, 38.80]	0.068
Platelet, 10^9/L	168.00 [129.00, 211.00]	167.50 [131.00, 208.25]	169.00 [128.00, 215.00]	0.042
Hemoglobin, g/L	124.00 [109.00, 137.00]	124.00 [109.00, 137.25]	123.00 [106.00, 136.00]	0.047
INR	1.12 [1.03, 1.28]	1.14 [1.04, 1.29]	1.11 [1.02, 1.25]	0.096
CTP score	5.00 [3.00, 6.00]	5.00 [4.00, 6.00]	4.00 [3.00, 5.00]	0.789
CrCl, mL/min	45.07 [31.37, 58.14]	44.83 [31.92, 58.24]	45.53 [31.06, 57.57]	0.034
APTT, s	31.90 [29.30, 35.20]	31.85 [29.20, 35.10]	31.90 [29.60, 35.30]	0.129
FIB, g/L	3.35 [2.84, 3.96]	3.31 [2.82, 3.93]	3.43 [2.87, 3.99]	0.12
TT, s	15.70 [14.80, 16.60]	15.80 [14.80, 16.70]	15.70 [14.80, 16.60]	0.075
DD, μg/L	602.50 [296.00, 1188.75]	563.00 [291.25, 1185.00]	643.00 [316.25, 1204.25]	0.027
In-hospital treatment
Dosing_regimen (%)				0.249
10mg qd	619 (62.2)	401 (64.1)	226 (59.2)
15mg qd	273 (27.1)	152 (24.3)	121 (31.7)
20mg qd	51 (5.1)	33 (5.3)	18 (4.7)
5mg qd	23 (2.3)	19 (3.0)	4 (1.0)
2.5mg bid	19 (1.9)	13 (2.1)	6 (1.6)
15mg bid	7 (0.7)	4 (0.6)	3 (0.8)
10mg bid	5 (0.5)	3 (0.5)	2 (0.5)
7.5mg qd	2 (0.2)	0 (0.0)	2 (0.5)
2mg qd	1 (0.1)	1 (0.2)	0 (0.0)
Course /days (median [IQR])	6 [4, 8]	6 [4, 8]	5 [4, 8]	0.143
Co-medication
Concomitant use of PPIs n(%)	436 (43.3)	265 (42.3)	171 (44.8)	0.049
Concomitant use of amiodarone n(%)	146 (14.5)	102 (16.3)	44 (11.5)	0.138
Concomitant use of AAD n(%)	10 (1.0)	9 (1.4)	1 (0.3)	0.128
Concomitant use of anti-platelet drugs n(%)	206 (20.4)	148 (23.6)	58 (15.2)	0.215
Concomitant use of NSAIDs n(%)	67 (6.6)	38 (6.1)	29 (7.6)	0.06

Note: ^aHigh school and above is defined as high level of educational attainment.

Abbreviations: ASD, absolute standardized difference; BMI, body mass index; IQR, interquartile range; INR, international normalized ratio; CTP, child-turcotte-pugh; CrCl, creatinine clearance; APTT, activated partial thromboplastin time; TT, thrombin time; FIB, fibrinogen; DD, D-dimer; qd, once daily; bid, twice daily; PPIs, proton pump inhibitors; AAD, azole antifungal drugs; NSAIDs, non-steroidal anti-inflammatory drugs.

Table 2 The Incidence, Severity and Sites of Bleeding Events

Variables	Total (n=1008)	Brand Group (n=626)	Generic Group (n=382)
Bleeding_events (%)
No	868 (86.1)	550 (87.9)	318 (83.2)
Yes	140 (13.9)	76 (12.1)	64 (16.8)
Bleeding_severity (%)
\	868 (86.1)	550 (87.9)	318 (83.2)
Minor	117 (11.6)	61 (9.7)	56 (14.7)
CRNM	17 (1.7)	11 (1.8)	6 (1.6)
Major	6 (0.6)	4 (0.6)	2 (0.5)
Bleeding_site (%)
\	868 (86.1)	550 (87.9)	318 (83.2)
Gastrointestinal bleeding	62 (6.2)	37 (5.9)	25 (6.5)
Hematuresis	58 (5.8)	28 (4.5)	30 (7.9)
Subcutaneous hemorrhage	7 (0.7)	2 (0.3)	5 (1.3)
Other sites	6 (0.6)	4 (0.6)	2 (0.5)
Epistaxis	4 (0.4)	3 (0.5)	1 (0.3)
Intracranial hemorrhage	3 (0.3)	2 (0.3)	1 (0.3)

Abbreviation: CRNM, clinically relevant non-major.

Figure 2 Comparing the bleeding risk of brand and generic rivaroxaban.

Abbreviations: OR, odds ratios; CI, confidence intervals; PSM, propensity-score matching; IPTW, inverse probability of treatment weighting.