TABLE 1

Noninferiority clinical trials with direct oral anticoagulants for the acute and long-term therapy of pulmonary embolism (PE)

Drug	Trial	Design	Treatments	Duration	Patients	Severity evaluation for PE
Rivaroxaban	EINSTEIN-PE [48]	Open	Rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)	3, 6 or 12 months	4832 patients with PE	Anatomical extension of PE
Rivaroxaban	EINSTEIN-PE [48]	Open	Enoxaparin/warfarin	3, 6 or 12 months	4832 patients with PE	Tertiles of severity
Apixaban	AMPLIFY [52]	Double blind	Apixaban (10 mg twice daily for 7 days, then 5 mg twice daily)	6 months	1836 patients with PE	Anatomical extension of PE
Apixaban	AMPLIFY [52]	Double blind	Enoxaparin/warfarin	6 months	1836 patients with PE	Anatomical extension of PE
Edoxaban	HOKUSAI [53]	Double blind	LMWH/edoxaban (60 mg once daily)	<12 months	3319 patients with PE	NT-proBNP levels (2989 patients)
Edoxaban	HOKUSAI [53]	Double blind	UFH or LMWH/warfarin	<12 months	3319 patients with PE	Right ventricle dilation at CT (1002 patients)
Dabigatran	RE-COVER I and RE-COVER II [50, 51]	Double blind	Enoxaparin/dabigatran (150 mg twice daily)	6 months	1602 patients with PE	Not reported
Dabigatran	RE-COVER I and RE-COVER II [50, 51]	Double blind	Enoxaparin/warfarin	6 months	1602 patients with PE	Not reported

AMPLIFY: Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy; LMWH: low-molecular-weight heparin; UFH: unfractionated heparin; NT-proBNP: N-terminal pro-brain natriuretic peptide.