TABLE 16.
Bleeding Events (Percentage Per Year) in DOAC Pivotal Clinical Trials
| Bleeding Event | RE-LY (n=18,113) | ARISTOTLE (n=18,201) | ENGAGE AF-TIMI 48 (n=21,105) | ROCKET AF (n=14,264) |
|---|---|---|---|---|
| Major bleeding | Dabigatran 150 mg 3.11% (RR, 0.93 [95% CI, 0.81-1.07]; P=0.31) Dabigatran 110 mg 2.71% (RR, 0.80 [95% CI, 0.69-0.93]; P=0.003) Warfarin 3.36% |
Apixaban 2.13% (HR, 0.69 [95% CI, 0.60-0.80]; P<0.001) Warfarin 3.09% |
Edoxaban 60 mg 2.75% vs warfarin 3.43% (HR, 0.80 [95% CI, 0.71-0.91]; P<0.001) Edoxaban 30 mg 1.61% vs warfarin 3.43% (HR, 0.47 [95% CI, 0.41-0.55]; P<0.001) |
Rivaroxaban 3.6% vs warfarin 3.4% (HR, 1.04 [95% CI, 0.90-1.20]; P=0.58) |
| Gastrointestinal bleeding | Dabigatran 150 mg 1.51% vs warfarin 1.02% (RR, 1.50 [95% CI, 1.19-1.89]; P<0.001) Dabigatran 110 mg 1.12% vs warfarin 1.02% (RR, 1.10 [95% CI, 0.86-1.41]; P=0.43) |
Apixaban 0.76% (HR, 0.89 [95% CI, 0.70-1.15]; P=0.37) Warfarin 0.86% |
Edoxaban 60 mg 1.51% (HR, 1.23 [95% CI, 1.02-1.50] ; P=0.03) Edoxaban 30 mg 0.82% (HR, 0.67 [95% CI, 0.53-0.83]; P<0.001) Warfarin 1.23% |
Rivaroxaban 3.2% (HR not reported; P<0.001) Warfarin 2.2% |
| Intracranial bleeding | Dabigatran 150 mg 0.30% (RR, 0.40 [95% CI, 0.27-0.60]; P<0.001) Dabigatran 110 mg 0.23% (RR, 0.31 [95% CI, 0.20-0.47]; P<0.001) Warfarin 0.74% |
Apixaban 0.33% (HR, 0.42 [95% CI, 0.30-0.58]; P<0.001) Warfarin 0.80% |
Edoxaban 60 mg 0.39% (HR, 0.47 [95% CI, 0.34-0.63]; P<0.001) Edoxaban 30 mg 0.26% (HR, 0.30 [95% CI, 0.21-0.43]; P<0.001) Warfarin 0.85% |
Rivaroxaban 0.80% (HR, 0.67 [95% CI, 0.47-0.93]; P=0.02) Warfarin 1.20% |
Adapted with permission from Kido et al.22 Copyright 2021 American College of Clinical Pharmacy.
ARISTOTLE indicates Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; DOAC, direct anticoagulant; ENGAGE AF-TIMI 48, Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation – Thrombolysis in Myocardial Infarction 48; HR indicates hazard ratio; 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; and RR, relative risk.