Rivaroxaban for venous thromboembolism prevention after major orthopedic surgery: translating trial data into routine clinical practice

Figures & data

Table 1 Key clinical outcomes from the RECORD and XAMOS studies

Outcome	RECORD1–4 pooled^Citation8,a,b			XAMOS^Citation11,c
	Rivaroxaban (N=6,183)	Enoxaparin (N=6,200)	OR (95% CI)	Rivaroxaban (N=8,778)	SOC (N=8,635)	OR (95% CI)
Symptomatic VTE, % (n)	0.45 (28)	1.1 (68)	0.4d (0.26–0.64)	0.65 (57)	1.02 (88)	0.63 (0.45–0.89)
All-cause mortality, % (n)	0.13 (8)	0.26 (16)	0.5d (0.21–1.16)	0.08 (7)	0.09 (8)	0.86 (0.31–2.37)
Major bleeding, % (n)b,e	0.39 (24)	0.21 (13)	1.84 (0.94–3.62)	0.4 (35)	0.34 (29)	1.19 (0.73–1.95)
Leading to reoperation	0.19 (12)	0.11 (7)	ND	0.31 (27)	0.21 (18)	ND
All other serious AEs, % (n)	6.57 (406)	8.52 (528)	ND	3.09 (271)	3 (259)	ND
Wound complications, % (n)
Postoperative wound infection	0.44 (27)	0.45 (28)	ND	0.15 (13)	0.08 (7)	1.83 (0.68–5.41)
Postoperative wound discharge	0.1 (6)	<0.1 (3)	ND	0.42 (37)	0.12 (10)	3.65 (1.78–8.24)
Hemorrhagic wound complicationsf	1.62 (100)	1.69 (105)	ND	0.47 (41)	0.42 (36)	1.12 (0.71–1.76)

Notes:

a Safety population, total treatment-duration pool;

b period of data collection was the total treatment-duration pool, defined as the planned treatment period for the double-blind study medication for each RECORD study;

c safety population;

d hazard ratio;

e RECORD major bleeding definition;

f for total treatment-duration pool, RECORD and XAMOS – treatment-emergent hemorrhagic wound complications.

Abbreviations: AE, adverse event; CI, confidence interval; ND, not determined; OR, odds ratio; SOC, standard of care; VTE, venous thromboembolism.

Table 2 Key clinical outcomes from ORTHO-TEP

Outcome	Rivaroxaban (N =1,043)		LMWH (N=1,495)		Fondaparinux (N =1,994)
	% (n)	95% CI	% (n)	95% CI	% (n)	95% CI
Symptomatic VTE	2.11 (22)	1.32–3.18	4.15 (62)	3.19–5.29	5.62 (112)	4.65–6.72
All-cause mortality	0.19 (2)	0.02–0.69	0.07 (1)	0.0017–0.37	0.15 (3)	0.03–0.44
Major bleeding	2.88 (30)	1.95–4.08	7.02 (105)	5.78–8.44	4.86 (97)	3.96–5.9
Surgical revisions due to bleeding complications	0.38 (4)	0.10–0.98	1.34 (20)	0.82–2.06	1.1 (22)	0.69–1.67
Any surgical revision	1.15 (12)	0.6–2	3.68 (55)	2.78–4.76	1.65 (33)	1.14–2.32

Notes: Adapted from: Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopedic surgery: findings from the ORTHO-TEP registry. J Thromb Haemost. 2012;10(10):2045–2052. © 2012 International Society on Thrombosis and Haemostasis.¹⁶ And adapted from: Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery. Thromb Haemost. 2013;109(1):154–163. © 2013 Schattauer Publishers, Stuttgart.¹⁷

Abbreviations: CI, confidence interval; LMWH, low-molecular-weight heparin; VTE, venous thromboembolism.

Table 3 Summary of other rivaroxaban studies

Study	Design, numbers	Comparator drug	Key findings
Rates of hospitalization for VTE and major bleeding after THA/TKA in patients >66 years of age^Citation18	Multicenter retrospective, N=24,321	LMWH	VTE was significantly less frequent with rivaroxaban compared with LMWH, with similar rates of major bleeding
Comparison of surgically relevant wound complications in patients undergoing prophylaxis after THA/TKA^Citation13	Multicenter prospective, N=2,762	LMWH	Patients in the rivaroxaban group had a significantly higher wound-complication rate and lower DVT rate than those in the LMWH group, with no significant differences in PE or all-cause mortality
Effect of rivaroxaban prophylaxis on return-to-theater rates following THA/TKA^Citation12	Single-center retrospective, N=1,048	Tinzaparin	Return-to-theater rate was significantly higher with tinzaparin than with rivaroxaban
Rivaroxaban use in patients after THA/TKA in “everyday life”^Citation20	Nonrandomized controlled, N=1,028	LMWH	Rivaroxaban was more effective than weight-adjusted nadroparin in preventing VTE after THA/TKA
Rates of PE recurrence and return-to-theater complications after TKA^Citation30	Single-center retrospective, N=862	Enoxaparin 40 mg once daily	Significant reduction in the rate of PE with rivaroxaban compared with control but an increase in return-to-theater rates
Efficacy and safety of rivaroxaban vs bemiparin in extended VTE prophylaxis^Citation50	Single-center retrospective, N=467	Bemiparin 3,500 IU IV/day	Discontinuation outcomes showed that oral administration promoted better treatment adherence compared with subcutaneous administration
Comparison of return-to-theater complications after THA/TKA with rivaroxaban vs enoxaparin^Citation14	Single-center retrospective, N=387	Enoxaparin 40 mg once daily	No significant difference in wound complications between groups
Rate of postoperative wound complications in patients undergoing prophylaxis after THA^Citation19	Single-center retrospective, N=258	Enoxaparin 40 mg once daily	Rivaroxaban showed no significant difference in the incidence of VTE or major bleeding but did show a trend toward increased rate of wound complications
Comparison of rivaroxaban and enoxaparin after minimally invasive TKA surgery^Citation29	Retrospective, N=113	Enoxaparin 20 mg every 12 hours (plus all patients received tranexamic acid 10 mg/kg IV)	No differences in postoperative hemoglobin levels, blood-drainage amount, total blood loss, or transfusion rate between rivaroxaban and enoxaparin were found; no VTE event or major wound complications occurred in either group
Efficacy of rivaroxaban in preventing VTE after pelvic trauma with immediate/delayed thromboprophylaxis^Citation21	Single-center retrospective, N=84	Delayed thromboprophylaxis with rivaroxaban 10 mg	Patients receiving rivaroxaban thromboprophylaxis soon after fracture had a lower incidence than if delayed; rivaroxaban did not increase intra- or postoperative bleeding in surgical wounds
Effect of tranexamic acid on blood loss with rivaroxaban treatment after orthopedic surgery^Citation22	Single-blind prospective, N=70	Rivaroxaban 10 mg once daily (tranexamic acid 1 g IV) was added to one group of patients receiving the rivaroxaban 10 mg dose	Tranexamic acid significantly reduced blood loss without increasing the risk of VTE

Note: Experimental dose in each study: rivaroxaban 10 mg once daily.

Abbreviations: DVT, deep vein thrombosis; IV, intravenous; LMWH, low-molecular-weight heparin; PE, pulmonary embolism; THA, total hip arthroplasty; TKA, total knee arthroplasty; VTE, venous thromboembolism.

Figure 1 Kaplan–Meier analysis of length of hospital stay with rivaroxaban and fondaparinux.

Notes: Subgroups of patients without complications (A), with and without VTE (B), with and without major bleeding (C), and with and without surgical revisions (D). Owing to the interference of complications and confounding factors over time, these analyses are of a descriptive nature only, and were not assessed for statistical significance. Adapted with permission from the Journal of Thrombosis and Haemostasis (John Wiley & Sons Ltd, Chichester, UK). Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopedic surgery: findings from the ORTHO-TEP registry. 2012;10(10):2045–2052. © 2012 International Society on Thrombosis and Haemostasis.¹⁶
Abbreviations: CI, confidence interval; VTE, venous thromboembolism.

Figure 2 Kaplan–Meier analysis of length of hospital stay with rivaroxaban and LMWH.

Notes: Subgroups of patients without complications (A), with and without VTE (B), with and without major bleeding (C), and with and without surgical revisions (D). Owing to the interference of complications and confounding factors over time, these analyses are of a descriptive nature only, and were not assessed for statistical significance. Adapted with permission from the Journal of Thrombosis and Haemostasis (Schattauer Publishers, Stuttgart, Germany). Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery: findings from the ORTHO-TEP registry. 2013;109(1):154–163. © Schattauer Publishers, Stuttgart.¹⁷
Abbreviations: LMWH, low-molecular-weight heparin; VTE, venous thromboembolism.

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