New oral pharmacotherapeutic agents for venous thromboprophylaxis after total hip arthroplasty

Table 3 Phase III clinical trials of target specific oral anticoagulants (target specific oral anticoagulants)

Clinical trial	TSOA regimen(duration)	Enoxaparinregimen(duration)	Composite of total venous thromboembolism and death		P-value,non-inferiority (superiority)	Major bleeding		P-value
			TSOA %(n/N)	Enoxaparin %(n/N)		TSOA %(n/N)	Enoxaparin %(n/N)
RE-NOVATE[54] (N = 3494)	Dabigatran 220 mg daily (28-35 d) Dabigatran 150 mg daily (28-35 d)	40 mg daily (28-35 d)	220 mg; 3.1% (28/909) 150 mg; 8.6% (75/874)	6.0% (53/880)	< 0.0001 (n/a) < 0.0001 (n/a)	220 mg; 2.0% (23/1146) 150 mg; 1.3% (15/1163)	1.6% (18/1154)	0.44 0.6
RE-NOVATE II[47] (N = 2055)	Dabigatran 220 mg daily (28-35 d)	40 mg daily (28-35 d)	7.7% (61/792)	8.8% (69/785)	< 0.0001 0.43	1.4% (14/1010)	0.9% (9/1003)	0.4
RECORD 1[62] (N = 4541)	Rivaroxaban 10 mg daily (31-39 d)	40 mg daily (31-39 d)	1.1% (18/1595)	3.7% (58/1558)	n/a (< 0.001)	0.3% (6/2209)	0.1% (2/2224)	0.18
RECORD 2[63] (N = 2509)	Rivaroxaban 10 mg daily (31-39 d)	40 mg daily (10-14 d)	2.0% (17/864)	9.3% (81/869)	n/a (< 0.0001)	0.08% (1/1228)	0.08% (1/1229)	n/a
ADVANCE 3[73] (N = 5407)	Apixaban 2.5 mg BID (32-38 d)	40 mg daily (32-38 d)	1.4% (27/1949)	3.9% (74/1917)	< 0.001 (< 0.001)	0.8% (22/2673)	0.7% (18/2659)	0.54
STARS J-5[75] (N = 610)	Edoxaban 30 mg daily (11-14 d)	20 mg BID (11-14 d)	2.4% (6/255)1	6.9% (17/248)1	< 0.001 0.016	2.6% (8/303)2	3.7% (11/301)2	0.48

¹All events were asymptomatic DVT.

²Rate of major and clinically relevant non-major bleeding. TSOA: Target specific oral anticoagulant; RE-NOVATE: The extended thromboembolism prevention after hip surgery; RECORD: Regulation of Coagulation in Orthopedic Surgery to Prevent DVT and PE; STARS: Studying thrombosis after replacement surgery.