Table 2.

Non-valvular atrial fibrillation: comparison of NOAC phase III trials

	RE-LY	ROCKET-AF	ARISTOTLE	ENGAGE-AF
Comparison	Dabigatran 150 mg bd, 110 mg bd vs warfarin	Rivaroxaban 20 mg od vs warfarin	Apixaban 5 mg bd vs warfarin	Edoxban 60 mg od, 30 mg od vs warfarin
Patients, n	18,113	14,264	18,201	21,105
Study design	Double blind, open-label with blinded endpoint evaluation	Double blind, double dummy	Double blind, double dummy	Double blind, double dummy
Reduced dose for selected patients	_	15 mg od: CrCl 30–49 mL/min	2.5 mg bd where two of: serum creatinine ≥1.5 mg/dL age ≥80 years body weight ≤60 kg	Dose halved (30 mg, 15 mg) where one of: CrCl 30–50 mL/min, body weight ≤60 kg concomitant verapamil, quinidine or dronedarone
Mean patient age, years	71	73	70 (median)	72
Mean CHADS₂ score	2.1	3.5	2.1	2.8
Mean time in therapeutic range, %	64.0	55.0	62.2	64.9
Valve exclusion	Severe valve disorder	Significant MS; any prosthesis	Moderate/Severe MS; mechanical	Moderate/Severe MS; mechanical
Paroxysmal AF, %	32	18	15	25
Primary endpoint SSE HR (95% CI)*	150 mg: 0.65 (0.52– 0.81)^s 110 mg: 0.90 (0.74–1.10)	0.88 (0.75–1.03)	0.79 (0.66–0.95)^s	60 mg: 0.79 (0.63–0.99) 30 mg: 1.07 (0.87–1.31)
Ischaemic stroke HR (95% CI)*	150 mg: 0.76 (0.60– 0.98)^s 110 mg: 1.11 (0.89–1.40)	0.94 (0.75–1.17)	0.92 (0.74–1.13)	60 mg: 1.00 (0.83–1.19) 30 mg: 1.41 (1.19–1.67)
Major bleeding HR (95% CI)*	150 mg: 0.93 (0.81–1.07) 110 mg: 0.80 (0.70–0.93)^s	1.04 (0.90–1.20)	0.69 (0.60–0.80)^s	60 mg: 0.80 (0.71–0.91) 30 mg: 0.47 (0.41–0.55)
Major gastrointestinal bleeding HR (95% CI)*	150 mg: 1.48 (1.18–1.85) 110 mg: 1.08 (0.85-1.38)	1.61 (1.30–1.99)	0.89 (0.70–1.15)	60 mg: 1.23 (1.02–1.50) 30 mg: 0.67 (0.53–0.83)^s
Intracranial bleeding HR (95% CI)*	150 mg: 0.40 (0.27–0.60)^s 110 mg: 0.31 (0.20–0.47)^s	0.67 (0.47–0.93)^s	0.42 (0.30–0.58)^s	60 mg: 0.47 (0.34–0.63)^s 30 mg: 0.30 (0.21–0.43)^s
Reduction in all-cause mortality	150 mg: 0.88 (0.77–1.00) 110 mg: 0.91 (0.80–1.03)	0.85 (0.70–1.02)	0.89 (0.80–0.99)	60 mg: No 30 mg: Yes

All comparisons versus warfarin and reached non-inferiority, unless otherwise stated.
↵*Data for dabigratran are presented as relative risk (95% CI)
^SSuperior
AF = atrial fibrillation; CHADS₂ = congestive heart failure, hypertension history, age≥75 years, diabetes mellitus history, stroke or symptoms of transient ischaemic attack; CI = confidence interval; CrCl = creatinine clearance; HR = hazard ratio; MS = mitral stenosis; NOAC = non-vitamin K oral anticoagulant; SSE = stroke or systemic embolism