Table 4.
Main study outcomes in trials of novel oral anticoagulants versus warfarin
| |
RE-LY[41,53] |
ROCKET-AF[52] |
ARISTOTLE[49] |
||||
|---|---|---|---|---|---|---|---|
| DABI 110 | DABI 150 | WARF | RIVA | WARF | APIX | WARF | |
| Stroke or systemic embolus, %/y |
1.54 |
1.11 |
1.71 |
1.7b |
2.2b |
1.27 |
1.60 |
| |
|
|
|
2.1c |
2.4c |
||
| HR (95% CI) |
0.65 (0.52, 0.81)a |
0.79 (0.66, 0.96)b |
0.79 (0.66, 0.95) |
||||
| |
|
|
|
0.88 (0.75, 1.03)c |
|||
| |
35 |
21 |
21 |
||||
| Risk reduction, % (P value) |
(<0.001 for noninferiority; <0.001 for superiority)a |
(<0.001 for noninferiority)b; 12 (<0.001 for noninferiority; 0.12 for superiority)c |
(<0.001 for noninferiority; 0.01 for superiority) |
||||
| Ischemic stroke, %/y |
1.34 |
0.92 |
1.21 |
1.34d |
1.42d |
0.97 |
1.05 |
| HR (95% CI) |
0.76 (0.59, 0.97)a |
0.94 (0.75, 1.17) |
0.92 (0.74, 1.13) |
||||
| Risk reduction, % (P value) |
24 (0.03)a |
6 (0.581) |
8 (0.42) |
||||
| Hemorrhagic stroke, %/y |
0.12 |
0.10 |
0.38 |
0.26d |
0.44d |
0.24 |
0.47 |
| HR (95% CI) |
0.26 (0.14, 0.49)a |
0.59 (0.37, 0.93) |
0.51 (0.35, 0.75) |
||||
| Risk reduction, % (P value) |
74 (<0.001)a |
41 (0.024) |
49 (<0.001) |
||||
| Major bleeding, %/y |
2.87 |
3.32 |
3.57 |
3.6d,e |
3.4d,e |
2.13 |
3.09 |
| HR (95% CI) |
0.93 (0.81, 1.07)a |
1.04 (0.90, 1.20) |
0.69 (0.60, 0.80) |
||||
| Risk reduction, % (P value) |
7 (0.31)a |
−4 (0.58) |
31 (<0.001) |
||||
| Intracranial bleeds, %/y |
0.23 |
0.32 |
0.76 |
0.5d |
0.7d |
0.33 |
0.80 |
| HR (95% CI) |
0.41 (0.28, 0.60)a |
0.67 (0.47, 0.93) |
0.42 (0.30, 0.58) |
||||
| Risk reduction, % (P value) |
59 (<0.001)a |
33 (0.02) |
58 (<0.001) |
||||
| Major GI bleeds, %/y |
1.15 |
1.56 |
1.07 |
3.15d,f |
2.16d,f |
0.76 |
0.86 |
| HR (95% CI) |
1.48 (1.18, 1.85)a |
– |
0.89 (0.70, 1.15) |
||||
| Risk reduction, % (P value) |
−52 (0.001)a |
<0.001 |
11 (0.37) |
||||
| Total mortality, %/y |
3.75 |
3.64 |
4.13 |
4.5c |
4.9c |
3.52 |
3.94 |
| HR (95% CI) |
0.88 (0.77, 1.00)a |
0.92 (0.82, 1.03) |
0.89 (0.80, 0.998) |
||||
| Risk reduction, % (P value) |
12 (0.051)a |
8 (0.15) |
11 (0.047) |
||||
| Warfarin mean TTR, % | – | – | 64 | – | 55 | – | 62 |
aRelative risk for DABI 150 mg versus WARF. bPer-protocol analysis. c Intent-to-treat analysis. dAs-treated safety population. eAny major bleeding; however, the primary safety endpoint in ROCKET-AF was combined rate of major and clinically relevant nonmajor bleeding (14.9%/y for rivaroxaban, 14.5%/y for warfarin; HR (95% CI) 1.03 (0.96, 1.11); P = 0.44. fProportion of patients with GI bleeding, not %/y.
Abbreviations: APIX apixaban, ARISTOTLE Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, CI confidence interval, DABI dabigatran, GI gastrointestinal, HR hazard ratio, RE-LY Randomized Evaluation of Long-Term Anticoagulation Therapy, RIVA rivaroxaban, ROCKET-AF Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation, TTR time in therapeutic range, WARF warfarin.