Selected distinctions among pivotal randomized controlled trials of NOAC for stroke prevention in nonvalvular in AF
| . | RE-LY20 . | ROCKET-AF21 . | ARISTOTLE22 . | ENGAGE AF-TIMI 4823 . | AVERROES30 . |
|---|---|---|---|---|---|
| Comparison | Dabigatran twice daily (110 mg, 150 mg)* vs warfarin (open-label) | Rivaroxaban 20 mg daily vs warfarin | Apixaban 5 mg twice daily vs warfarin | Edoxaban daily (30 mg, 60 mg)* vs warfarin | Apixaban 5 mg twice daily vs aspirin |
| No. of patients (approx.) | 18 000 | 14 000 | 18 000 | 21 000 | 5600 |
| Valve exclusion | Severe valve disorder | Significant MS; any prosthesis | Mod/sev MS; mechanical | Mod/sev MS; mechanical | Requires surgery; mechanical |
| Renal exclusion | CrCl < 30 mL/min | CrCl < 30 mL/min | Cr > 2.5 mg/dL or CrCl < 25 mL/min | CrCl < 30 mL/min | Cr > 2.5 mg/dL or CrCl < 25 mL/min |
| Protocol-specified dose-reduction for renal impairment | None | CrCl 15-50 mL/min: 15 mg daily | ≥2 of following age >80, weight <60 kg, Cr >1.5 mg/dL (2.5 mg twice daily) | ≥1 of the following: CrCl 30-50 mL/min, weight ≤60 kg, concomitant use of potent P-glycoprotein inhibitors (halved dose) | ≥2 of following age >80, weight <60 kg, Cr >1.5 mg/dL (2.5 mg twice daily) |
| CHADS2, mean | 2.1 | 3.5 | 2.1 | 2.8 | 2.0 |
| Triple therapy allowed (OAC+DAPT)28 | Yes | No | No | No | No |
| Stroke outcomes | Noninferior (110 mg), superior (150 mg) | Noninferior | Superior | Noninferior | Superior |
| Bleeding outcomes | Superior (110 mg), noninferior (150 mg) | Noninferior (ICH/fatal vs GI) | Superior | Superior | Not significantly different |
| All-cause mortality reduced | No | No | Yes | Yes (30 mg), | No |
| No (60 mg) |
| . | RE-LY20 . | ROCKET-AF21 . | ARISTOTLE22 . | ENGAGE AF-TIMI 4823 . | AVERROES30 . |
|---|---|---|---|---|---|
| Comparison | Dabigatran twice daily (110 mg, 150 mg)* vs warfarin (open-label) | Rivaroxaban 20 mg daily vs warfarin | Apixaban 5 mg twice daily vs warfarin | Edoxaban daily (30 mg, 60 mg)* vs warfarin | Apixaban 5 mg twice daily vs aspirin |
| No. of patients (approx.) | 18 000 | 14 000 | 18 000 | 21 000 | 5600 |
| Valve exclusion | Severe valve disorder | Significant MS; any prosthesis | Mod/sev MS; mechanical | Mod/sev MS; mechanical | Requires surgery; mechanical |
| Renal exclusion | CrCl < 30 mL/min | CrCl < 30 mL/min | Cr > 2.5 mg/dL or CrCl < 25 mL/min | CrCl < 30 mL/min | Cr > 2.5 mg/dL or CrCl < 25 mL/min |
| Protocol-specified dose-reduction for renal impairment | None | CrCl 15-50 mL/min: 15 mg daily | ≥2 of following age >80, weight <60 kg, Cr >1.5 mg/dL (2.5 mg twice daily) | ≥1 of the following: CrCl 30-50 mL/min, weight ≤60 kg, concomitant use of potent P-glycoprotein inhibitors (halved dose) | ≥2 of following age >80, weight <60 kg, Cr >1.5 mg/dL (2.5 mg twice daily) |
| CHADS2, mean | 2.1 | 3.5 | 2.1 | 2.8 | 2.0 |
| Triple therapy allowed (OAC+DAPT)28 | Yes | No | No | No | No |
| Stroke outcomes | Noninferior (110 mg), superior (150 mg) | Noninferior | Superior | Noninferior | Superior |
| Bleeding outcomes | Superior (110 mg), noninferior (150 mg) | Noninferior (ICH/fatal vs GI) | Superior | Superior | Not significantly different |
| All-cause mortality reduced | No | No | Yes | Yes (30 mg), | No |
| No (60 mg) |
ARISTOTLE, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; AVERROES, Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; Cr, creatinine; CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; ENGAGE AF-TIMI 48, Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48; GI, gastrointestinal; 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.
US Food and Drug Administration–approved dose for stroke prevention in AF is 150 mg twice daily for dabigatran (75 mg twice daily for CrCl 15-30 mL/min), 60 mg daily for edoxaban (30 mg for those with CrCl 15-50 mL/min; edoxaban is contraindicated for stroke prevention in AF for patients with CrCl >95 mL/min), and 60 mg daily for edoxaban.