| |
Mean duration of treatment
|
Recurrent venous thromboembolism
|
Nonmajor clinically relevant and major bleeding
|
Major bleeding
|
Net clinical benefit
|
|---|
|
Patient group
|
Rivaroxaban
|
Enoxaparin/VKA
|
Rivaroxaban n/N (%)
|
Enoxaparin/VKA n/N (%)
|
HR (95% CI)
|
Rivaroxaban n/N (%)
|
Enoxaparin/VKA n/N (%)
|
HR (95% CI)
|
Rivaroxaban n/N (%)
|
Enoxaparin/VKA n/N (%)
|
HR (95% CI)
|
Rivaroxaban n/N (%)
|
Enoxaparin/VKA n/N (%)
|
HR (95% CI)
|
|---|
| |
Days ± SD
|
Days ± SD
| | | | | | | | | | | | |
|---|
|
All
|
207.6 ± 95.9
|
204.0 ± 97.2
|
86/4150 (2.1)
|
95/4131 (2.3)
|
0.89 (0.66–1.19)
|
388/4130 (9.4)
|
412/4116 (10.0)
|
0.93 (0.81–1.06)
|
40/4130 (1.0)
|
72/4116 (1.7)
|
0.54 (0.37–0.79)
|
134/4150 (3.2)
|
169/4131 (4.1)
|
0.77 (0.61–0.97)
|
|
Fragile
|
196.8 ± 97.5
|
187.2 ± 102.5
|
21/791 (2.7)
|
30/782 (3.8)
|
0.68 (0.39–1.18)
|
97/788 (12.3)
|
109/779 (14.0)
|
0.85 (0.64–1.11)
|
10/788 (1.3)
|
35/779 (4.5)
|
0.27 (0.13–0.54)*
|
36/791 (4.6)
|
66/782 (8.4)
|
0.51 (0.34–0.77)†
|
|
Nonfragile
|
210.1 ± 95.4
|
208.0 ± 95.5
|
65/3359 (1.9)
|
65/3349 (1.9)
|
0.98 (0.69–1.38)
|
291/3342 (8.7)
|
303/3337 (9.1)
|
0.95 (0.81–1.12)
|
30/3342 (0.9)
|
37/3337 (1.1)
|
0.80 (0.49–1.29)
|
98/3359 (2.9)
|
103/3349 (3.1)
|
0.93 (0.71–1.23)
|
|
Cancer
|
179.0 ± 96.9
|
167.7 ± 103.1
|
16/316 (5.1)
|
20/281 (7.1)
|
0.69 (0.36–1.33)
|
48/316 (15.2)
|
44/278 (15.8)
|
0.93 (0.62–1.41)
|
9/316 (2.8)
|
14/278 (5.0)
|
0.53 (0.23–1.23)
|
26/316 (8.2)
|
37/281 (13.2)
|
0.60 (0.36–0.99)
|
|
No cancer
|
209.3 ± 95.6
|
205.8 ± 96.6
|
70/3834 (1.8)
|
75/3850 (1.9)
|
0.93 (0.67–1.29)
|
340/3820 (8.9)‡
|
368/3832 (9.6)‡
|
0.92 (0.79–1.06)
|
31/3820 (0.8)‡
|
58/3832 (1.5)‡
|
0.53 (0.34–0.82)
|
108/3834 (2.8)
|
132/3850 (3.4)
|
0.81 (0.63–1.05)
|
|
Previous DVT/PE
|
259.0 ± 102.0
|
252.6 ± 107.1
|
11/791 (1.4)
|
25/819 (3.1)
|
0.45 (0.22–0.91)§
|
70/788 (8.9)
|
91/813 (11.2)
|
0.77 (0.57–1.06)
|
7/788 (0.9)
|
14/813 (1.7)
|
0.51 (0.21–1.27)
|
20/791 (2.5)
|
39/819 (4.8)
|
0.52 (0.31–0.90)
|
|
No previous DVT/PE
|
195.4 ± 90.3
|
192.0 ± 90.8
|
75/3359 (2.2)
|
70/3312 (2.1)
|
1.04 (0.75–1.45)
|
318/3342 (9.5)
|
321/3303 (9.7)
|
0.96 (0.82–1.12)
|
33/3342 (1.0)
|
58/3303 (1.8)
|
0.54 (0.35–0.83)
|
114/3359 (3.4)
|
130/3312 (3.9)
|
0.84 (0.66–1.08)
|
|
Clot burden (limited)¶
|
197.6 ± 93.2
|
197.1 ± 94.1
|
10/799 (1.3)
|
19/815 (2.3)
|
0.51 (0.24–1.10)
|
73/796 (9.2)
|
76/813 (9.3)
|
0.97 (0.70–1.34)
|
8/796 (1.0)
|
11/813 (1.4)
|
0.75 (0.30–1.87)
|
20/799 (2.5)
|
30/815 (3.7)
|
0.65 (0.37–1.16)
|
|
Clot burden (intermediate)¶
|
215.0 ± 94.5
|
206.1 ± 96.4
|
41/1873 (2.2)
|
49/1881 (2.6)
|
0.82 (0.54–1.24)
|
181/1864 (9.7)
|
189/1876 (10.1)
|
0.95 (0.78–1.17)
|
20/1864 (1.1)
|
32/1876 (1.7)
|
0.62 (0.36–1.09)
|
65/1873 (3.5)
|
81/1881 (4.3)
|
0.79 (0.57–1.10)
|
|
Clot burden (extensive)¶
|
205.8 ± 97.8
|
205.2 ± 100.0
|
35/1364 (2.6)
|
26/1327 (2.0)
|
1.29 (0.78–2.15)
|
126/1359 (9.3)
|
134/1326 (10.1)
|
0.90 (0.71–1.15)
|
11/1359 (0.8)
|
28/1326 (2.1)
|
0.36 (0.18–0.73)
|
48/1364 (3.5)
|
56/1327 (4.2)
|
0.81 (0.55–1.19)
|
- *For major bleeding, the p-value for the treatment group × fragility interaction was 0.011, suggesting heterogeneity. †For net clinical benefit, the p-value for the treatment group × fragility interaction was 0.017. ‡In this analysis, six DVT patients were randomized to rivaroxaban but received comparator. §For recurrent VTE, the p-value for the treatment group × previous DVT/PE was 0.032. For all other outcomes and analyses the interactions between treatment group and the subgroups of fragility [yes/no], baseline cancer [yes/no], previous DVT/PE [yes/no], clot burden for outcomes [limited/intermediate/extensive]), the pinteractions were larger than 0.05 (nonsignificant) calculated by the corresponding Cox proportional hazards models. ¶In the clot burden analysis, a total of 71 patients in the rivaroxaban group and 68 patients in the enoxaparin/VKA group had missing data. A further 43 and 40 patients in the rivaroxaban and enoxaparin/VKA groups, respectively, did not have confirmed DVT and PE.
- CI Confidence interval, DVT Deep vein thrombosis, HR Hazard ratio, PE Pulmonary embolism, VKA Vitamin K antagonist.
