Thromboprophylaxis with apixaban and the risk of pulmonary embolism in patients undergoing knee replacement surgery

Figures & data

Table 1 Baseline characteristics of the included randomized clinical trials

	ADVANCE I		ADVANCE II		ADVANCE III
Parameters	Apixaban	Enoxaparin	Apixaban	Enoxaparin	Apixaban	Enoxaparin
Mean age (years)	65.9	65.7	65.6	65.9	60.9	60.6
Female gender n (%)	997 (62)	986 (62)	1089 (71)	1127 (74)	1430 (53)	1451 (54)
Mean duration of hospitalization (days)	6.3	6.4	11.5	11.7	9.3	9.2
History of VTE n (%) Deep-vein thrombosis/pulmonary embolism	57 (4)/10 (1)	47 (3)/6 (<1)	36 (2)/10 (<1)	32 (2)/10 (<1)	41 (2)/17 (1)	47 (2)/11 (<1)
Estimated creatinine clearance >50 ml/min n (%)	1388 (86.8)	1377 (86.3)	1386 (91)	1399 (91)	2563 (95)	2557 (95)
Duration of prophylaxis	10–14 days		10–14 days		35 days
Dose of apixaban/enoxaparin (mg)	2.5 twice daily/30 twice daily		2.5 twice daily/40 once daily		2.5 twice daily/40 once daily
Primary efficacy outcome	Asymptomatic and symptomatic DVT, non-fatal PE, death from any cause during treatment		Asymptomatic and symptomatic DVT, non-fatal PE, death from any cause during treatment		Asymptomatic and symptomatic DVT, non-fatal PE, death from any cause during treatment
Safety outcome	Major or clinically relevant non-major bleeding		Major or clinically relevant non-major bleeding		Major or clinically relevant non-major bleeding
Follow-up period	60 days after treatment		60 days after treatment		60 days after treatment
Time when apixaban started	12–24 h post-surgery		12–24 h after wound closure		12–24 h after wound closure
Time when enoxaparin started	12–24 h post-surgery		12 h prior to surgery		12 h prior to surgery
Type of surgery	Total knee replacement		Total knee replacement		Hip replacement
Method for identifying DVT	Bilateral venography		Bilateral venography		Bilateral venography
Methods for identifying PE	VQ scan, Spiral CT or pulmonary angiography		V-Q, Spiral CT or pulmonary angiography		V-Q, Spiral CT or pulmonary angiography

Fig. 1 Flow chart describing systematic literature search and study selection process.

Fig. 2 Meta-analysis of symptomatic DVT. Comparator: apixaban versus enoxaparin.

Fig. 3 Meta-analysis of bleeding events. Comparator: apixaban versus enoxaparin.

Fig. 4 Meta-analysis of pulmonary embolism. Comparator: apixaban versus enoxaparin.