Table 4. Review of the Landmark Trials in Atrial Fibrillation and the Use of Novel Anticoagulants^28–34

Drug	Trial	Design	Treatment	Duration	TTR (%)	Patients	Mean CHAD₂ Score	Efficacy/Outcome	Safety/Outcome
Dabigatran	RE-LY	Blinded	VKA/dabigatran (150 mg bid)	24 months	64	18,113 patients with nonvalvular Afib	2.1	Stroke or systemic emboli, 1.11% Dabigatran 1.69% VKA group	Major bleeding in 2.71% Dabigatran in 3.36% of VKA group
Rivaroxaban	Rocket AF	DB	VKA/rivaroxaban (20 mg daily)	30 months	55	14,264 patients with nonvalvular Afib	3.5	Stroke or systemic emboli 1.7% rivaroxaban 2.2% VKA group	Major bleeding: 3.6% in rivaroxaban group, 3.4% in VKA group
Rivaroxaban	X-Vert	DB	VKA/rivaroxaban (20 mg daily)	Months	55	1504 patients needed cardioversion for Afib	3.2	Stroke or systemic emboli: 0.5% in rivaroxaban group and 1.02 in the VKA group	Major bleeding: 0.61% in rivaroxaban group vs 0.8% in VKA group
Apixaban	AVVEROUS	DB	ASA/apixaban 5 mg bid or 2.5 mg bid	13 months	62	5,599 patients with nonvalvular Afib could not take warfarin	2.1	Stroke or systemic emboli: 1.6% in apixaban group vs 3.7% in the ASA group	Major bleeding: 1.4% in apixaban group vs 1.2% in ASA group
	ARISTOTLE	DB	VKA/apixaban 5 mg bid or 2.5 mg bid	22 months	62	18,201 patients with nonvalvular Afib	2.1	Stroke or systemic emboli 1.27% apixaban 1.6% VKA group	Major bleeding 2.1 apixaban 3.09% VKA group
Edoxaban	ENGAGE-TIMI 48	DB	VKA/edoxaban 60 mg daily and 30 mg daily	34 months	64	21,105 patients with nonvalvular Afib	2.8	Stroke or systemic emboli: 1.18% in edoxaban group vs 1.5% in VKA group	Major bleeding: 2.75% in edoxaban group vs 3.43% in VKA group

Afib, atrial fibrillation; ASA, aspirin; DB, double blind; TTR, time in therapeutic range; VKA, Vitamin K antagonist.