Table 2.
Summary of bleeding outcomes of DOACs from phase 3 clinical trials for the prevention of stroke and SEE in patients with NVAF [19–22].
| Major bleeding | Intracranial bleeding | Gastrointestinal bleeding | ||||
|---|---|---|---|---|---|---|
| N | HR (95% CI) | N | HR (95% CI) | N | HR (95% CI) | |
| (%) | P value | (%) | P value | (%) | P value | |
| RE-LY | ||||||
| Dabigatran 150 mg BID | 375 | 0.93 (0.81–1.07) | 36 | 0.40 (0.27–0.60) | 182 | 1.50 (1.19–1.89) |
| (n = 6076) | (3.11) | 0.31 | (0.30) | <0.001 | (1.51) | <0.001 |
| Dabigatran 110 mg BID | 322 | 0.80 (0.69–0.93) | 27 | 0.31 (0.20–0.47) | 133 | 1.10 (0.86–1.41) |
| (n = 6015) | (2.71) | 0.003 | (0.23) | <0.001 | (1.12) | 0.43 |
| Warfarin | 397 | 87 | 120 | |||
| (n = 6022) | (3.36) | (0.74) | (1.02) | |||
| ROCKET AF | ||||||
| Rivaroxaban 20 mg QDa | 395 | 1.04 (0.90–1.20) | 55 | 0.67 (0.47–0.93) | 224 | NR |
| (n = 7111) | (5.60) | 0.58 | (0.80) | 0.02 | (3.15) | |
| Warfarin | 386 | 84 | 154 | |||
| (n = 7125) | (5.40) | (1.20) | (2.16) | |||
| ARISTOTLE | ||||||
| Apixaban 5 mg BIDb | 327 | 0.69 (0.60–0.80) | 52 | 0.42 (0.30–0.58) | 105 | 0.89 (0.70–1.15) |
| (n = 9088) | (2.13) | <0.001 | (0.33) | <0.001 | (0.76) | 0.37 |
| Warfarin | 462 | 122 | 119 | |||
| (n = 9052) | (3.09) | (0.80) | (0.86) | |||
| ENGAGE AF-TIMI 48 | ||||||
| Edoxaban 60 mg QD | 418 | 0.80 (0.71–0.91) | 61 | 0.47 (0.34–0.63) | 232 | 1.23 (1.02–1.50) |
| (n = 7012) | (2.75) | <0.001 | (0.39) | <0.001 | (1.51) | 0.03 |
| Edoxaban 30 mg QD | 254 | 0.47 (0.41–0.55) | 41 | 0.30 (0.21–0.43) | 129 | 0.67 (0.53–0.83) |
| (n = 7002) | (1.61) | <0.001 | (0.26) | <0.001 | (0.82) | <0.001 |
| Warfarin | 524 | 132 | 190 | |||
| (n = 7012) | (3.43) | (0.85) | (1.23) | |||
a15 mg QD in patients with creatinine clearance 30–49 mL/min.
b2.5 mg BID in patients meeting 2 or more of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥15 mg/L.
ARISTOTLE, apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation; BID, twice daily; CI, confidence interval; DOACs, direct-acting oral anticoagulants; ENGAGE AF-TIMI 48, effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction 48; HR, hazard ratio; NR, not reported; QD, once daily; NVAF, nonvalvular atrial fibrillation; RE-LY, randomized evaluation of long-term anticoagulation therapy; 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; SEE, systemic embolic event.