Background
Materials and methods
Study design
Selection of study population
Study endpoints
Statistical analysis
Results
Patient disposition
Characteristic
| Edoxaban 30 mg QD (n = 255) | Enoxaparin 2000 IU BID (n = 248) |
---|---|---|
Sex
| ||
Female | 220 (86.3) | 212 (85.5) |
Age (y)
| ||
Mean ± SD | 62.8 ± 9.61 | 62.8 ± 9.72 |
<75 | 220 (86.3) | 217 (87.5) |
≥75 | 35 (13.7) | 31 (12.5) |
Weight (kg)
| ||
Mean ± SD | 57.7 ± 9.72 | 57.0 ± 9.60 |
<60 | 160 (62.7) | 157 (63.3) |
≥60 | 95 (37.3) | 91 (36.7) |
BMI, mean ± SD | 24.5 ± 3.52 | 24.2 ± 3.60 |
CL
CR
(mL/min) | ||
Mean ± SD | 89.6 ± 29.58 | 88.9 ± 26.49 |
≥80 | 148 (58.0) | 150 (6) |
≥50 to <80 | 93 (36.5) | 91 (36.7) |
<50 | 14 (5.5) | 7 (2.8) |
History of artificial joint replacement of the lower limbs
| 39 (15.3) | 35 (14.1) |
Duration from the end of surgery to the start of study treatment (h)
| ||
≥12 to <18 | 16 (6.3) | - |
≥18 to ≤24 | 239 (93.7) | - |
≥24 to <30 | - | 170 (68.5) |
≥30 to <36 | - | 78 (31.5) |
Hour:minute, Mean ± SD | 21:40 (1:54) | 28:37 (3:00) |
Physiotherapy
a
| ||
Intermittent pneumatic compression therapy (foot sole) | 137 (53.7) | 135 (54.4) |
Intermittent pneumatic compression therapy (lower legs and thigh) | 120 (47.1) | 114 (46.0) |
Elastic stockings | 209 (82.0) | 201 (81.0) |
Concomitant NSAIDs
| 250 (98.0) | 243 (98.0) |
Treatment duration (days)
| ||
Mean ± SD | 12.5 (1.4) | 12.5 (1.5) |
Outcome measures
Outcome | Edoxaban 30 mg QD (n = 255) | Enoxaparin 2000 IU BID (n = 248) | Absolute difference % (95 % CI) | ||
---|---|---|---|---|---|
n (%) | 95 % CI | n (%) | 95 % CI | ||
Primary efficacy (any VTE) | 6 (2.4) | 1.1, 5.0 | 17 (6.9) | 4.3, 10.7 | −4.5 (−8.6, −0.9)a,b
|
Asymptomatic DVT | |||||
Totalc
| 6 (2.4) | 1.1, 5.0 | 17 (6.9) | 4.3, 10.7 | −4.5 (−8.6, −0.9) |
Proximal | 1 (0.4) | 0.1, 2.2 | 2 (0.8) | 0.2, 2.9 | −0.4 (−2.5, 1.5) |
Distal | 6 (2.4) | 1.1, 5.0 | 16 (6.5) | 4.0, 10.2 | −4.1 (−8.1, −0.6) |
Symptomatic DVT | 0 (0.0) | 0.0, 1.5 | 0 (0.0) | 0.0, 1.5 | 0.0 |
Symptomatic PE | 0 (0.0) | 0.0, 1.5 | 0 (0.0) | 0.0, 1.5 | 0.0 |
VTE-related death | 0 (0.0) | 0.0, 1.5 | 0 (0.0) | 0.0, 1.5 | 0.0 |
Symptomatic DVT, proximal DVT, symptomatic PE, or VTE-related death | 1 (0.4) | 0.1, 2.2 | 2 (0.8) | 0.2, 2.9 | −0.4 (−2.5, 1.5) |
Safety
Event | Edoxaban 30 mg QD (n = 303) | Enoxaparin 2000 IU BID (n = 301) | Absolute difference % (95 % CI) |
P
| ||
---|---|---|---|---|---|---|
n (%) | 95 % CI | n (%) | 95 % CI | |||
Major bleeding | 2 (0.7) | 0.2, 2.4 | 6 (2.0) | 0.9, 4.3 | −1.3 (−3.7, 0.7) | 0.176 |
Subcutaneous hemorrhage | 1 (0.3) | NC | 2 (0.7) | NC | NC | NC |
Wound hemorrhage | 1 (0.3) | - | 1 (0.3) | - | - | - |
Duodenal ulcer hemorrhage | 0 (0.0) | - | 2 (0.7) | - | - | - |
Hemarthrosis | 0 (0.0) | - | 1 (0.3) | - | - | - |
CRNM bleeding | 6 (2.0) | 0.9, 4.3 | 5 (1.7) | 0.7, 3.8 | 0.3 (−2.1, 2.8) | 0.769 |
Subcutaneous hemorrhage | 1 (0.3) | NC | 0 (0.0) | NC | NC | NC |
Wound hemorrhage | 1 (0.3) | - | 0 (0.0) | - | - | - |
Conjunctival hemorrhage | 1 (0.3) | - | 0 (0.0) | - | - | - |
Epistaxis | 1 (0.3) | - | 0 (0.0) | - | - | - |
Lower gastrointestinal hemorrhage | 1 (0.3) | - | 0 (0.0) | - | - | - |
Hematuria | 1 (0.3) | - | 1 (0.3) | - | - | - |
Postprocedural hematoma | 0 (0.0) | - | 3 (1.0) | - | - | - |
Subcutaneous hematoma | 0 (0.0) | - | 1 (0.3) | - | - | - |
Major or CRNM bleeding | 8 (2.6) | 1.3, 5.1 | 11 (3.7) | 2.1, 6.4 | −1.0 (−4.1, 1.9) | 0.475 |
Minor bleeding | 57 (18.8) | 14.8, 23.6 | 39 (13.0) | 9.6, 17.2 | 5.9 (0.0, 11.7) | 0.049 |
Any bleeding | 62 (20.5) | 16.3, 25.4 | 48 (15.9) | 12.2, 20.5 | 4.5 (−1.7, 10.7) | 0.151 |
Edoxaban 30 mg QD (n = 303) | Enoxaparin 2000 IU BID (n = 301) | |
---|---|---|
Adverse events
| ||
Patients with events | 197 (65.0) | 232 (77.1) |
95 % CI | 59.5, 70.2 | 72.0, 81.5 |
Number of events | 448 | 676 |
Adverse events reported by ≥5 % of patients in either treatment group
a
| ||
ALT increased | 36 (11.9) | 126 (41.9) |
AST increased | 17 (5.6) | 97 (32.2) |
γ-glutamyltransferase increased | 44 (14.5) | 79 (26.2) |
Blood urine present | 38 (12.5) | 34 (11.3) |
Blood alkaline phosphatase increased | 14 (4.6) | 40 (13.3) |
Hemorrhage subcutaneous | 12 (4.0) | 21 (7.0) |
Adverse drug reactions
| ||
Patients with events | 121 (39.9) | 177 (58.8) |
95 % CI | 34.6, 45.5 | 53.2, 64.2 |
Number of events | 198 | 439 |
Hepatic function test parameter
| ||
ALT or AST | ||
≥1.5 x ULN | 43 (14.2) | 135 (44.9) |
≥3 x ULN | 8 (2.6) | 30 (10.0) |
≥5 x ULN | 2 (0.7) | 11 (3.7) |