Table 2.
Comparison of novel oral anticoagulant trials
| Dabigatran11 | Rivaroxaban14 | Apixaban12,13 | Edoxaban16 | |
|---|---|---|---|---|
| Key clinical trial(s) | RE-LY | ROCKET-AF | AVERROES, ARISTOTLE | ENGAGE-AF TIMI-48 |
| Trial design | Randomized, double-blind, prospective, open-label (PROBE) | Randomized, prospective double-blind, double-dummy | Randomized, prospective double-blind, double-dummy | Randomized, prospective, double-blind, double-dummy |
| Primary efficacy endpoint | Stroke or SE | Stroke or SE | Stroke or SE | Stroke or SE |
| Primary safety endpoint | Major bleeding (ISTH) | Major (ISTH)/CRNM bleeding | Major bleeding (AVERROES,a ARISTOTLEa) | Major bleeding (ISTH) |
| Trial dose | 150 mg bid or 110 mg bid | 20 mg/d | 5 mg bid | 60 mg/d 30 mg/d |
| Reduced dose for selected patients | NA | 15 mg/d (CrCl 30–49 mL/min) | 2.5 mg bidb | Dose halved in selected patientsc |
| Mean CHADS2 score | 2.1 | 3.5 | 2.1 | Not stated |
| Mean TTR, % | 64 | 55 | 62.2 | 64.9 |
Notes:
Defined according to ISTH criteria, adjusted for the decrease in hemoglobin level if a blood transfusion is required
reduced dose if patients met two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine level ≥1.5 mg/day
for patients in either group the dose was halved if any of the following symptoms were present at the time of randomization or at any point during the study: estimated creatinine clearance 30–50 mL/min, body weight ≤60 kg, or the concomitant use of verapamil or quinidine (potent P-glycoprotein inhibitors). A protocol amendment mandated similar dose modification in the case of concomitant dronedarone use.
Abbreviations: CHADS2, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes, Stroke (doubled); CrCl, creatinine clearance; CRNM, clinically relevant nonmajor; ISTH, International Society on Thrombosis and Haemostasis; NA, not applicable; SE, systemic embolism; TTR, time in therapeutic range; ARISTOTLE, Apixaban for Reduction In Stroke and Other ThromboemboLic Events in atrial fibrillation; AVERROES, Apixaban Versus Acetylsalicylic acid (ASA) to Prevent Strokes; RE-LY, Randomized Evaluation of Long-Term Anticoagulation Therapy; ROCKET-AF, Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation; ENGAGE-AF TIMI-48, Edoxaban versus Warfarin in Patients with Atrial Fibrillation; bid, twice daily.