Table 3.

Key aspects of the non-vitamin K antagonist anti-coagulant phase III clinical trials [40–43]

Trial	Dosing	Design	Patients enrolled (n)	Mean CHADS2 scorea	Median follow-up (years)	Mean percent TTR
RE-LY
Dabigatran	110 or 150 mg, bid	Non-inferiority, prospective, randomized, open-label for warfarin, blinded for dabigatran	18,113	2.1	2.0	64
Warfarin	Dose adjusted to INR 2.0–3.0
ROCKET AF
Rivaroxaban	20 mg od, 15 mg daily in pts with ClCr 30–49 ml/min	Non-inferiority, prospective, randomized double-blind, double-dummy, parallel-arm	14,264	3.5	1.9	55
Warfarin	Dose adjusted to INR 2.0–3.0
ARISTOTLE
Apixaban	5 mg bid; 2.5 mg bid in pts with ≥2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dl (133 μmol/l)	Non-inferiority, prospective, randomized double-blind, double-dummy, parallel-arm	18,201	2.1	1.8	62
Warfarin	Dose adjusted to INR 2.0–3.0
ENGAGE AF
Edoxaban	60 or 30 mg od; 50 % dose reduction for pts with a ClCr 30–50 ml/min, body weight ≤60 kg, or concomitant treatment with P-gp inhibitors	Non-inferiority, prospective, randomized double-blind, double-dummy, parallel-arm	21,105	2.8	2.8	65
Warfarin	Dose adjusted to INR 2.0–3.0

bid twice daily, CI confidence interval, Cl _Cr creatinine clearance, CRNM clinically relevant non-major, INR international normalized ratio, od once daily, P-gp P-glycoprotein, pts patients, TTR time in therapeutic range

^aIn ROCKET AF, INRs calculated 7 days after randomization and during treatment interruptions were excluded from calculation