Table 1.
Bleeding outcomes in pivotal trials utilizing DOACs*
| Dabigatran
|
Rivaroxaban
|
Apixaban
|
Edoxaban
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
|
Stroke prevention in NVAF
| ||||||||||||
| Trial |
RE-LY4
|
ROCKET-AF5
|
ARISTOTLE6
|
ENGAGE-TIMI 487
|
||||||||
| 110 mg | 150 mg | 30 mg | 60 mg | |||||||||
|
| ||||||||||||
| Stroke or SE | 0.91 (0.74–1.11) |
<0.001 (for NI); 0.34 (for S) |
0.66 (0.53–0.82) |
<0.001 (for NI and for S) |
0.88 (0.75–1.03) |
<0.001 (for NI) |
0.79 (0.66–0.95) |
0.01 | 1.07 (0.87–1.31) |
0.005 (for NI) |
0.79 (0.63–0.99) |
<0.001 (for NI) |
| Major or CRNM bleeding | 0.78 (0.74–0.83) |
<0.001 | 0.91 (0.86–0.97) |
0.002 | 1.03 (0.96–1.11) |
0.44 | 0.68 (0.61–0.75) |
<0.001 | 0.62 (0.57–0.67) |
<0.001 | 0.86 (0.80–0.92) |
<0.001 |
| Major bleeding | 0.80 (0.69–0.93) |
0.003 | 0.93 (0.81–1.07) |
0.31 | 1.04 (0.90–1.20) |
0.58 | 0.69 (0.60–0.80) |
<0.001 | 0.47 (0.41–0.55) |
<0.001 | 0.80 (0.71–0.91) |
<0.001 |
| Intracranial | 0.31 (0.20–0.47) |
<0.001 | 0.40 (0.27–0.60) |
<0.001 | 0.67 (0.47–0.93) |
0.02 | 0.42 (0.30–0.58) |
<0.001 | 0.30 (0.21–0.43) |
<0.001 | 0.47 (0.34–0.63) |
<0.001 |
| GI bleeding | 1.10 (0.86–1.41) |
0.43 | 1.50 (1.19–1.89) |
<0.001 | 3.2% vs 2.2% | <0.001 | 0.89 (0.70–1.15) |
0.37 | 0.67 (0.53–0.83) |
<0.001 | 1.23 (1.02–1.50) |
0.03 |
|
| ||||||||||||
| Acute VTE treatment | ||||||||||||
|
| ||||||||||||
| Trial |
RE-COVER8
|
EINSTEIN DVT-PE11
|
AMPLIFY12
|
Hokusai-VTE13
|
||||||||
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |||||
|
| ||||||||||||
| Recurrent VTE | 1.10 (0.65–1.84) |
NR | 0.89 (0.66–1.19) |
<0.001 (for NI) |
0.84 (0.60–1.18) |
<0.001 (for NI) |
0.89 (0.70–1.13) |
<0.001 (for NI) |
||||
| Major or CRNM bleeding | 0.63 (0.47–0.84) |
NR | 0.93 (0.81–1.06) |
0.27 | 0.44 (0.36–0.55) |
<0.001 | 0.81 (0.71–0.94) |
0.004 | ||||
| Major bleeding | 0.82 (0.45–1.48) |
NR | 0.54 (0.37–0.79) |
0.002 | 0.31 (0.17–0.55) |
<0.001 | 0.84 (0.59–1.21) |
0.35 | ||||
| Intracranial | 0 vs 3 | NR | 2 vs 4 | NR | 0.1% vs 0.2% | NR | NR | NR | ||||
| GI bleeding | 53 vs 35 | NR | 1 vs 3 | NR | 0.3% vs 0.7% | NR | NR | NR | ||||
Note:
*
Comparator agent for each is warfarin, listed as HR, number of patients, or percentage of patients.
Abbreviations: CRNM, clinically relevant nonmajor; DOAC, direct oral anticoagulant; GI, gastrointestinal; HR, hazard ratio; NI, non-inferiority; NR, not reported; NVAF, nonvalvular atrial fibrillation; S, superiority; SE, systemic embolism; VTE, venous thromboembolism.