Table 2.

Outcomes with direct oral anticoagulants compared with vitamin K antagonists in patients with creatinine clearance between 30 and 50 ml/min and atrial fibrillation or with direct oral anticoagulants compared with low-molecular weight heparin/ vitamin K antagonists in patients with creatinine clearance between 30 and 50 ml/min and venous thromboembolism.

Indication	Trial	DOAC – dose	N	Outcome	HR (95% CI)
Atrial fibrillation	ARISTOTLE10	Apixaban 5 bid*	3017	Stroke/embolism	0.79 (0.55–1.14)
				Major bleeding	0.50 (0.38–0.66)
	ENGAGE TIMI 4811	Edoxaban 30 qd	2740	Stroke/embolism	0.87 (0.65–1.18)
				Major bleeding	0.76 (0.58–0.98)
	ROCKET AF12	Rivaroxaban 15 qd	2950	Stroke/embolism	0.84 (0.57–1.23)
				Major bleeding	0.98 (0.73–1.30)
	RE-LY13	Dabigatran 110 bid	3374	Stroke/embolism	0.85 (0.59–1.24)
				Major bleeding	0.99 (0.77–1.28)
		Dabigatran 150 bid		Stroke/embolism	0.56 (0.37–0.85)
				Major bleeding	1.01 (0.79–1.30)
Venous thromboembolism	AMPLIFY14	Apixaban 10 bid × 7 days, then 5 bid	338	Recurrent VTE or VTE-related death	0.93 (0.34–2.61)¶
				Major bleeding	0.52 (0.18–1.51)¶
	HOKUSAI-VTE15	Edoxaban 30 qd	363	Recurrent VTE	0.49 (0.19–1.27)¶
				Major bleeding	0.66 (0.37–1.18)¶
	EINSTEIN16	Rivaroxaban 15 bid × 3 weeks, then 20 qd	636	Recurrent VTE	1.05 (0.44–2.47)
				Major bleeding	0.23 (0.06–0.81)
	RE-COVER17	Dabigatran 150 bid	237	Recurrent VTE	-
				Major bleeding	6.71 (3.34–13.48)

^*, 2.5 mg bid if two of the three criteria are met: creatinine ≥1.5 mg/dl, body weight ≤60 kg, age ≥80

^¶, relative risk reported

N, total number of patients with chronic kidney disease; DOAC, direct oral anticoagulant; VKAs, vitamin K antagonists; bid, twice daily; HR, hazard ratio; CI, confidence interval; VTE, venous thromboembolism