Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

Table 3 Comparison of clinical trials on patients receiving direct oral anticoagulant: Major bleeding

	Dabigatran	Apixaban	Edoxaban	Rivaroxaban
Trial name	RE-LY[4]	ARISTOTLE[5]	ENGAGE AF TIMI48[6]	ROCKET AF[7]/J-ROCKET AF
Number of patients	18113	18201	21105	14264
Method	PROBE	RCT	RCT	RCT
Primary endpoints	Stroke or systemic embolism	Ischemic or hemorrhagic stroke or systemic embolism	Stroke or systemic embolism	Stroke or systemic embolism
Period (years)	2.0	1.8	2.8	1.9
CHADS2 score (mean)	2.2	2.1	2.8	3.48 (J-ROCKET: 3.25)
Dosing dose	150 mg/10 mg bid	5 mg bid	60 mg/30 mg qd	20 mg od (J-ROCKET: 15 mg od)
Evaluation
Thrombus/embolism (vs warfarin)	110 mg: Non-inferior, 150 mg: Superior	Superior	60 mg: Similar, 30 mg: Similar	On treatment: Superior, Intention-to-treat: Non-inferior
Outcomes: Stroke or systemic embolism	War: 1.69%/yr, D (110): 1.51%/yr, D (150): 1.11%/yr	War: 1.50%/yr, A: 1.27%/yr	War: 1.81%/yr, E (30): 2.06%/yr, E (60): 1.57%/yr	War: 2.2%/yr, R: 1.7%/yr
Major bleeding (vs warfarin)	110 mg: Superior, 150 mg: Similar	Superior	Superior	Similar
Bleeding rate	War: 3.36%/yr, D (110): 2.71%/yr, D (150): 3.11%/yr	War: 3.09%/yr, A: 2.13%/yr	War: 3.43%/yr, E (30): 1.61%/yr, E (60): 2.75%/yr	War: 3.4%/yr, R: 3.6%/yr
Intracranial bleeding	War: 0.74%/yr, D (110): 0.23%/yr, D (150): 0.30%/yr	War: 2.27%/yr, A: 1.79%/yr	War: 0.85%/yr, E (30): 0.26%/yr, E (60): 0.39%/yr	War: 0.7%/yr, R: 0.5%/yr
Gastrointestinal bleeding	War: 1.02%/yr, D (110): 1.12%/yr, D (150): 1.51%/yr	War: 0.86%/yr, A: 0.76%/yr	War: 1.23%/yr, E (30): 0.82%/yr, E (60): 1.51%/yr	War: 2.2%/yr, R: 3.2%/yr1
Minor bleeding (vs warfarin)	War: 16.37%/yr, D (110): 13.16%/yr, D (150): 14.84%/yr	War: 6.01%/yr, A: 4.07%/yr	War: 4.89%/yr, E (30): 3.52%/yr, E (60): 4.12%/yr	War: 11.4%/yr, R: 11.8%/yr
Mortality rate	War: 4.13%/yr, D (110): 3.75%/yr, D (150): 3.64%/yr	War: 3.94%/yr, A: 3.52%/yr	War: 4.35%/yr, E (30): 3.80%/yr, E (60): 3.99%/yr	War: 2.2%/yr, R: 1.9%/yr

A: Apixaban; D: Dabigatran; E: Edoxaban; R: Rivaroxaban; war: Warfarin; RCT: Randomized clinical trial; CHADS: Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, and Stroke; PROBE: Prospective randomized open blinded-endpoint.