Efficacy of 11 anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and network meta-analysis : Medicine

Journal Logo

Research Article: Systematic Review and Meta-Analysis

Efficacy of 11 anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and network meta-analysis

Huang, Zhihao MPEa; Xu, Xinru MFEb; Xu, Dan MMc; Zhao, Pengfei PhDd,*; Zou, Miao MEDa

Author Information
Medicine 102(2):p e32635, January 13, 2023. | DOI: 10.1097/MD.0000000000032635

Abstract

1. Introduction

Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE),[1] with 10 million cases occurring every year,[2] represents the third most common acute cardiovascular syndrome (after myocardial infarction and stroke),[3] causes significant morbidity and mortality,[4] and places a substantial clinical and economic burden.[5] Total hip arthroplasty (THA) or total knee arthroplasty (TKA) is generally regarded as a highly successful surgical intervention that relieves pain, improves function, and enhances the quality of patients’ lives. However, VTE represents a major complication of this type of surgery. Among various methods of prophylaxis, the main approach involves anticoagulant prophylaxis. In addition, there are many kinds of anticoagulants, and there is no exact comparison of their anticoagulant effects. Therefore, in this study, we explored the effect of different anticoagulants on VTE prevention after THA or TKA through network meta-analysis, which is of great significance to guide clinical medical personnel to use scientific research results to prevent VTE.

2. Materials and methods

This review adhered to the Preferred Reporting in Systematic Reviews and Meta-Analysis 2020 guidelines,[6] and this review was registered in the International Prospective Register of Systematic Reviews (registration number, CRD42022357393).

3. Search strategy

A literature search was carried out by 2 independent reviewers. PubMed, Embase, The Cochrane Library, Web of Science, CBM, CNKI, WanFang Data, and VIP were explored from January 1, 2000, to January 27, 2022. To minimize the missing literature, references listed in the included studies were also traced to supplement relevant data.

4. Eligibility criteria

The inclusion criteria were as follows: administration of anticoagulants after THA or TKA (not limited by age, race, and nationality of patients); prospective or retrospective study design; direct or indirect availability of the results – responders and sample size.

The exclusion criteria were as follows: duplicate articles; articles with inconsistent research contents; review articles; conference abstracts; animal studies; case reports; study protocols; and non-English and non-Chinese articles.

4.1. Literature screening and data extraction

Two reviewers independently screened the literature and extracted and cross-checked the data. In case of disagreements, a third party was consulted to assist in the judgment. During literature screening, first, the title and abstract were read. Then, after the exclusion of irrelevant literature, the full text of the preliminarily relevant articles was read to determine whether to include them in the final analysis. Data extraction encompassed the basic characteristics of the included studies, such as author, publication year, country, anticoagulant, age, recipients, mean body mass index, duration of surgery, and surgery type. Results considered responders and sample size.

4.2. Statistical analysis

“Network” package of Stata 16.0 software was used to produce the network plot. The size of the nodes corresponds to the number of participants randomized to each treatment. Treatments with direct comparisons are linked with a line; its thickness corresponds to the number of trials evaluating the comparison. Frequentist network meta-analysis was conducted using the “netmeta” package in R 4.1.0 software. Transitivity was subjectively assessed by the basic characteristics of the included studies. I2 was used to analyze the heterogeneity. If I2 < 50%, there was little heterogeneity between the studies, and the fixed-effects model was used for pooling. If I2 ≥ 50%, there was great heterogeneity between the studies. Meta-regression was used to identify the potential factors causing heterogeneity, and then subgroup analysis was performed. If the source of heterogeneity could not be found, the random-effects model was used for pooling. Inconsistency was divided into global inconsistency and local inconsistency. Global Wald test was used to evaluate global inconsistency, and the node-splitting test was used to evaluate local inconsistency. If there was no statistically significant difference between the results of direct comparison and indirect comparison (P > .05), the consistency was good, and the consistency model was used for pooling; otherwise, the inconsistent model was used. Relative risk (RR) and 95% confidence interval (CI) were used to evaluate the efficacy of anticoagulants in the league table. P score was used to rank and compare different anticoagulants. The higher the P score value, the higher the efficacy ranking of the anticoagulant, and vice versa. The stability of the research results was analyzed by sensitivity analysis. The included studies were excluded one by one, and then meta-analysis was performed again. The results were compared with those before exclusion. If the change was small, it indicated that the stability of the included literature was good and the results were credible. If there were significant changes, it indicated that the results were not credible. A funnel plot was used to evaluate the existence of publication bias. If the P values of Egger, Begg–Mazumdar, and Thompson–Sharp tests were >.05, there was no publication bias; otherwise, there was publication bias.

4.3. Evidence assessment of the included studies

The reviewers assessed the certainty of evidence contributing to network estimates of the main outcomes using the Confidence in Network Meta-Analysis (CINeMA) framework,[7] which includes 6 domains: within-study bias, reporting bias, indirectness, imprecision, heterogeneity, and incoherence. Within-study bias was assessed by the modified Jadad score.[8] Potential sources of bias include random sequence production, allocation concealment, blinding method, and withdrawals and dropouts. According to the modified Jadad score, studies with a score ≤2 were considered studies without concerns; studies with a score 3 to 5 were considered studies with some concerns; and studies with a score ≥6 were considered studies with major concerns. Reporting bias was assessed subjectively in accordance with unpublished studies, outcomes in the gray literature, and funnel plots. Indirectness was subjectively assessed by the basic characteristics of the included studies. For imprecision, heterogeneity, and incoherence, relative effect estimates <0.800 and >1.250 were considered clinically important.

5. Results

5.1. Literature search and characteristics of the included studies

Sixteen anticoagulants were searched preliminarily by referring to relevant literature, and a total of 4150 articles were identified by searching the databases. Additional 5 articles were identified during the screening of the reference sections of the included articles. The detailed information is shown in Supplemental Method S1, Supplemental Digital Content, https://links.lww.com/MD/I301. After the layer-by-layer screening, 61 articles[9–69] on 11 anticoagulants were finally included. The process and the results of the literature screening are shown in Figure 1. Detailed information on the included studies is shown in Table 1. The 11 anticoagulants included were apixaban, aspirin, betrixaban, dabigatran, darexaban, edoxaban, fondaparinux, low-molecular-weight heparin (LMWH), rivaroxaban, unfractionated heparin (UFH), and warfarin.

Table 1 - Characteristics of the included studies.
No. Study Country Anticoagulant Age Recipients (m/f) Mean body mass index (SD), kg/m2 Duration of surgery, h Surgery type
1 Anderson 2013 Canada LMWH 57.9 ± 12.2 400 (213/187) 27.9 ± 5.8 1.53 ± 0.82 THA
Aspirin 57.6 ± 11.9 385 (231/154) 29.3 ± 5.9 1.54 ± 0.62
2 Anderson 2018 Canada Rivaroxaban 60.9 ± 11.0 902 (480/422) 29.4 ± 5.8 1.4 ± 0.6 THA
Aspirin 61.3 ± 11.1 902 (486/416) 29.4 ± 6.0 1.4 ± 0.6
3 Anderson 2018 Canada Rivaroxaban 64.7 ± 8.4 815 (353/462) 32.7 ± 6.8 1.4 ± 0.5 TKA
Aspirin 64.6 ± 8.7 805 (318/487) 33.0 ± 7.2 1.4 ± 0.5
4 Argun 2013 Turkey Fondaparinux 58.7 ± 13.6 55 (21/34) NA NA THA & TKA
LMWH 60.0 ± 8.4 53 (20/33) NA NA
5 Bai 2018 China Rivaroxaban 69.28 ± 10.42 98 (50/48) 23.12 ± 3.29 NA THA
LMWH 68.33 ± 11.84 98 (49/49) 22.85 ± 2.85 NA
6 Bai 2020 China Rivaroxaban 70 ± 7 42 (4/38) 27 ± 3 NA TKA
LMWH 71 ± 8 42 (7/35) 27 ± 4 NA
7 Bai 2021 China Rivaroxaban 61.2 ± 11.7 (27–83) 114 (42/72) 25.7 ± 3.2 (20.1–29.7) NA THA
LMWH 61.9 ± 9.6 (32–82) 114 (51/63) 24.6 ± 3.1 (21.2–29.2) NA
8 Bauer 2001 USA Fondaparinux 67.5 ± 10.7 517 (204/313) 31.5 ± 6.5 2.12 ± 0.65 TKA
LMWH 67.5 ± 10.2 517 (223/294) 30.9 ± 6.2 2.13 ± 0.7
9 Bonneux 2006 Belgium Fondaparinux 66.9 ± 8.5 55 (12/43) 29.7 ± 5.2 NA TKA
LMWH 65.7 ± 10.4 54 (11/43) 29.8 ± 7.8 NA
10 Colleoni 2008 Brazil Aspirin 71.21 ± 6.35 14 (1/13) NA NA TKA
Rivaroxaban 67.11 ± 7.65 18 (4/14) NA NA
11 Ding 2014 China Rivaroxaban 56.5 ± 18.2 (35–72) 120 (78/42) NA NA THA
LMWH NA NA
12 Eriksson 2005 Sweden Dabigatran 65.9 (33–93) 393 (164/229) NA 1.4 (0.5–3.6) THA & TKA
LMWH 65.0 (20–86) 392 (151/241) NA 1.5 (0.4–4.6)
13 Eriksson 2006 Sweden Rivaroxaban 67 (51–87) 37 (16/21) 28 (21–38) 1.53 ± 0.55 THA
LMWH 65 (27–82) 132 (54/78) 28 (20–40) 1.37 ± 0.48
14 Eriksson 2007 Sweden Dabigatran 67 ± 9 679 (238/441) NA 1.52 ± 0.47 TKA
LMWH 68 ± 9 694 (216/478) NA 1.5 ± 0.47
15 Eriksson 2007 Sweden Dabigatran 67 ± 9 679 (238/441) NA 1.52 ± 0.47 TKA
LMWH 68 ± 9 694 (216/478) NA 1.5 ± 0.47
16 Eriksson 2007 Sweden Dabigatran 65 ± 10 1146 (510/636) NA 1.42 ± 0.48 THA
LMWH 64 ± 11 1154 (503/651) NA 1.45 ± 0.48
17 Eriksson 2007 Sweden Dabigatran 65 ± 10 1146 (510/636) NA 1.42 ± 0.48 THA
LMWH 64 ± 11 1154 (503/651) NA 1.45 ± 0.48
18 Eriksson 2007 Sweden Rivaroxaban 66 (32–84) 77 (32/45) 28 (18–38) NA THA
LMWH 64 (30–92) 162 (74/88) 28 (19–44) NA
19 Eriksson 2007 Sweden Darexaban NA NA NA NA THA
LMWH NA NA NA NA
20 Eriksson 2008 Sweden Rivaroxaban 63.1 (18–91) 2209 (989/1220) 27.8 (16.2–53.4) 1.51 (0.45–8.00) THA
LMWH 63.3 (18–93) 2224 (982/1242) 27.9 (15.2–50.2) 1.52 (0.42–5.75)
21 Eriksson 2010 Sweden Darexaban 61.3 (24–84) 163 (73/90) 28.5 (18.3–40.8) 1.39 (0.4–4.0) THA
LMWH 58.1 (22–85) 166 (80/86) 27.3 (18.4–41.4) 1.50 (0.5–3.4)
22 Eriksson 2011 Sweden Dabigatran 62 ± 12 1010 (469/541) 27.8 ± 4.8 1.33 (0.25–5.50) THA
LMWH 62 ± 11 1003 (502/501) 27.8 ± 4.8 1.32 (0.47–4.00)
23 Eriksson 2011 Sweden Dabigatran 62 ± 12 1010 (469/541) 27.8 ± 4.8 1.33 (0.25–5.50) THA
LMWH 62 ± 11 1003 (502/501) 27.8 ± 4.8 1.32 (0.47–4.00)
24 Fizgerald 2001 USA Warfarin NA 349 (153/196) NA NA THA
LMWH NA NA NA
25 Fuji 2014 Japan Edoxaban 72,6 ± 7.5 (36–84) 299 (54/245) NA 1.85 ± 0.63 (0.52–3.75) TKA
LMWH 72.1 ± 7.8 (30–84) 295 (66/229) NA 1.90 ± 0.53 (0.55–3.73)
26 Fuji 2014 Japan Darexaban 62.1 ± 10.48 136 (23/113) 23.92 ± 3.168 1.79 ± 0.702 THA
LMWH 61.6 ± 10.99 82 (20/62) 23.70 ± 3.704 1.68 ± 0.710
27 Fuji 2014 Japan Darexaban 71.2 ± 7.88 71 (9/62) 26.36 ± 3.850 1.82 ± 0.636 TKA
LMWH 72.3 ± 8.02 66 (9/57) 26.43 ± 3.407 1.80 ± 0.503
28 Fuji 2015 Japan Edoxaban 62.8 ± 9.61 255 (35/220) 24.5 ± 3.52 THA
LMWH 62.8 ± 9.72 248 (36/212) 24.2 ± 3.60
29 Gao 2011 China LMWH 66.1 (22–82) 166 (27/139) 26.79 ± 3.87 TKA
Aspirin 64.9 (40–84) 120 (21/99) 27.87 ± 3.62
30 Gao 2016 China LMWH 59.2 ± 7.7 (36–74) 54 (30/24) 23.6 ± 4.8 THA
Rivaroxaban 59.5 ± 7.8 (35–78) 54 (31/23) 23.4 ± 4.5
31 Ginsberg 2009 Canada Dabigatran 66.2 ± 9.5 857 (371/486) NA 1.52 ± 0.47 TKA
LMWH 66.3 ± 9.6 868 (364/504) NA 1.50 ± 0.47
32 Guo 2018 China LMWH 63.6 ± 2.5 (52–82) 60 (27/33) NA NA THA & TKA
Rivaroxaban NA NA
33 Hass 2006 Germany LMWH 66.1 ± 9.3 1013 (337/676) 27.8 ± 3.8 1.42 (0.50–5.33) THA & TKA
UFH 66.9 ± 9.8 1005 (350/655) 27.8 ± 3.9 1.42 (0.47–4.33)
34 Hosaka 2013 Japan Fondaparinux 73.3 ± 7.3 277 (31/246) 26.4 ± 3.9 1.89 ± 0.51 TKA
LMWH 72.8 ± 7.7 298 (31/267) 26.4 ± 5.2 1.89 ± 0.48
35 Hull 2000 Canada LMWH 64 ± 13 983 (467/516) 29 ± 6 THA
Warfarin 63 ± 13 489 (242/247) 28 ± 5
36 Jiang 2019 China Apixaban 68.7 ± 5.7 110 (62/48) 24.5 ± 3.2 1.84 ± 0.39 TKA
LMWH 70.2 ± 6.1 110 (52/58) 25.1 ± 3.5 1.76 ± 0.33
37 Kakkar 2000 UK LMWH 70.4 ± 10.9 149 (49/100) 25.3 ± 4.1 1.83 ± 0.92 THA
UFH 70.5 ± 9.2 149 (45/104) 25.6 ± 4.6 1.68 ± 0.98
38 Kakkar 2008 UK Rivaroxaban 61.4 ± 13.2 (18–93) 1228 (561/667) 26.8 ± 4.8 (15.6–54.7) 1.58 (0.50–7.92) THA
LMWH 61.6 ± 13.7 (19–93) 1229 (578/651) 27.1 ± 5.2 (15.5–59.0) 1.55 (0.47–9.92)
39 Kim 2016 South Korea Rivaroxaban 55.9 ± 14.30 350 (163/187) 25.0 ± 3.20 1.22 ± 0.45 THA
LMWH 56.0 ± 15.17 351 (174/177) 25.0 ± 3.59 1.25 ± 0.51
40 Lassen 2002 Denmark Fondaparinux 67 (30–90) 908 (396/512) 26 (15–45) 2·3 ± 0·80 THA
LMWH 67 (24–97) 919 (402/517) 26 (14–51) 2.4 ± 0.87
41 Lassen 2002 Denmark Fondaparinux 66 (29–92) 1140 (493/647) 26 (15–45) 2.3 ± 0.82 THA
LMWH 67 (24–97) 1133 (473/660) 27 (14–51) 2·4 ± 0·83
42 Lassen 2007 Denmark Apixaban 66.4 (46–84) 157 (54/103) 30.2 (22.5–50.2) 1.60 (0.62–7.73) TKA
LMWH 66.5 (36–88) 152 (58/94) 30.4 (18.8–46.0) 1.60 (0.70–3.33)
Warfarin 66.8 (43–85) 153 (60/93) 30.4 (20.8–50.1) 1.61 (0.67–4.17)
43 Lassen 2008 Denmark Rivaroxaban 67.6 (28–91) 1220 (363/857) 29.5 (16.3–51.1) 1.60 (0.43–8.33) TKA
LMWH 67.6 (30–90) 1239 (418/821) 29.8 (16.0–54.3) 1.62 (0.47–5.25)
44 Li 2018 China Rivaroxaban NA (35–75) 50 (13/37) NA NA THA & TKA
LMWH NA (36–75) 50 (21/29) NA NA
45 Migita 2014 Japan Fondaparinux 73.9 ± 8.0 (34–93) 1294 (221/1073) 25.4 ± 3.9 (14.5–44.0) 2.11 ± 0.62 (0.70–6.67) TKA
LMWH
UFH
46 Migita 2014 Japan Fondaparinux 66.7 ± 10.5 (23–94) 868 (128/740) 24.5 ± 3.9 (14.5–44.0) 2.06 ± 0.72 (0.58–5.53) THA
LMWH
UFH
47 Mirdamadi 2014 Iran LMWH 68.3 ± 10.1 45 (15/30) NA NA TKA
Dabigatran 72.1 ± 9.3 45 (17/28) NA NA
48 Qin 2016 China Rivaroxaban 60.5 ± 4.1 (36–79) 50 (29/21) NA NA THA
LMWH 61.1 ± 4.2 (37–78) 50 (28/22) NA NA
49 Quan 2010 China Rivaroxaban 63.9 ± 14.9 48 (13/35) 23.72 ± 2.61 NA THA & TKA
LMWH 57.2 ± 16.9 36 (10/26) 24.50 ± 2.07 NA
50 Rahman 2020 Egypt Rivaroxaban 42.95 ± 10.6 80 (36/44) 30.5 ± 4.80 1.67 ± 0.12 THA
LMWH 40.10 ± 14.7 80 (44/36) 29.8 ± 4.05 1.69 ± 0.13
51 Raskob 2010 USA LMWH 57.6 ± 12.41 175 (68/107) 27.10 ± 4.27 1.36 ± 0.45 THA
Edoxaban 58.3 ± 11.55 187 (68/119) 28.53 ± 4.82 1.39 ± 0.45
52 Ren 2021 China Aspirin 54.5 (40.8–62.3) 34 (13/21) 23.6 (20.7–25.5) NA THA
Rivaroxaban 50.0 (36.8–57.0) 36 (11/25) 23.5 (20.3–26.0) NA
53 Senaran 2005 Turkey LMWH 55.2 ± 8.4 50 (12/38) NA NA THA
UFH 52.4 ± 11.2 50 (17/33) NA NA
54 Shi 2014 China Rivaroxaban 65.14 ± 8.93 50 (10/40) 26.53 ± 3.56 NA TKA
LMWH 66.84 ± 6.90 25 (7/18) 27.19 ± 3.71 NA
55 Turpie 2002 Canada Fondaparinux 67 (26–92) 908 (386/401) 28 (14–73) 2.46 ± 0.95 THA
LMWH 67 (19–91) 919 (375/422) 27 (13–83) 2.42 ± 0.98
56 Turpie 2002 Canada Fondaparinux 67 (18–92) 1128 (556/572) 28 (14–73) 2.48 ± 0.95 THA
LMWH 67 (19–91) 1129 (522/607) 28 (13–83) 2.45 ± 0.95
57 Turpie 2005 Canada Rivaroxaban 67 (49–84) 103 (37/66) 31.8 ± 6.3 1.47 ± 0.57 TKA
LMWH 66 (47–83) 104 (47/57) 31.8 ± 6.0 1.51 ± 0.49
58 Turpie 2009 Canada Rivaroxaban 64.4 ± 9.7 1526 (519/1007) 30.9 ± 6.2 1.67 ± 0.71 TKA
LMWH 64.7 ± 9.7 1508 (541/967) 30.7 ± 6.0 1.67 ± 0.70
59 Turpie 2009 Canada Betrixaban 65 (47–75) 84 (32/52) NA NA TKA
LMWH 62 (43–75) 43(21/22) NA NA
60 Wang 2014 China Rivaroxaban 68.1 ± 0.5 (55–75) 60 (35/25) NA NA TKA
LMWH 67.5 ± 0.3 (57–73) 60 (36/24) NA NA
61 Wang 2017 China Rivaroxaban 69.3 ± 3.7 96 (27/69) 27.1 ± 4.4 1.43 ± 0.12 TKA
LMWH 70.7 ± 4.5 99 (34/65) 28.6 ± 3.9 1.51 ± 0.12
62 Wang 2020 China Rivaroxaban 64.18 ± 8.56 89 (40/49) 23.13 ± 1.60 NA THA
LMWH 63.70 ± 7.38 89 (44/45) 22.84 ± 1.45 NA
63 Weitz 2020 Canada LMWH 67.0 ± 8.8 76 (21/55) 32.4 ± 5.5 1.42 (1.08–1.82) TKA
Apixaban 64.9 ± 8.4 83 (18/65) 32.6 ± 5.8 1.42 (1.25–1.75)
64 Wu 2013 China Rivaroxaban 72.1 64 (25/39) NA NA THA
LMWH 74.7 64 (28/36) NA NA
65 Yang 2013 China Rivaroxaban 57.64 ± 10.22 75 (40/35) 24.28 ± 4.59 NA THA
LMWH 59.51 ± 10.65 70 (36/34) 23.80 ± 4.41 NA
66 Yokote 2011 Japan Fondaparinux 63.0 ± 10.0 84 (14/70) 22.5 ± 4.8 NA THA
LMWH 64.0 ± 11.0 83 (16/67) 23.0 ± 3.3 NA
67 Zhang 2017 China LMWH 58.36 ± 9.64 (47–69) 45 (26/19) NA NA THA
Rivaroxaban 56.68 ± 9.37 (45–68) 45 (27/18) NA NA
68 Zhang 2020 China LMWH 57.44 ± 9.89 43 (18/25) 26.11 ± 4.53 NA TKA
Rivaroxaban 59.72 ± 8.11 43 (21/22) 24.79 ± 3.48 NA
69 Zou 2014 China Rivaroxaban 63.5 (50–82) 102 (32/70) 27.5 (18.0–39.5) 1.42 (1.32–1.45) TKA
LMWH 65.7 (54–80) 112 (20/92) 27.0 (20.3–37.0) 1.41 (1.35–1.45)
Aspirin 62.7 (47–79) 110 (28/82) 27.8 (17.8–40.0) 1.51 (1.33–1.57)
LMWH = low molecular weight heparin, NA = , SD = standard deviation, THA = total hip arthroplasy, TKA = total knee arthroplasty, UFH = unfractionated heparin.

F1
Figure 1.:
Flow diagram of the literature search and selection processes.

5.2. Network meta-analysis

To visualize network geometry and node connectivity, network plots were produced for each outcome (Fig. 2). There was a similarity after carefully reviewing the included studies. Hence, the assumption of transitivity was likely to hold in the data. There was no heterogeneity for DVT outcome (I2 = 43.9%) or PE outcome (I2 = 0.0%); no global inconsistency for DVT outcome (global Wald test: P = .675) or PE outcome (global Wald test: P = .960); and no local inconsistency for DVT outcome (Table 2) or PE outcome (Table 3). Therefore, the consistency model and fixed model were used for pooling. Sixty-one articles with 67 studies were included for DVT outcome (Table 4). In terms of prevention of DVT, efficacy of apixaban was better than that of dabigatran (RR = 0.40, 95% CI [0.25–0.63]), LMWH (RR = 0.39, 95% CI [0.25–0.61]), aspirin (RR = 0.38, 95% CI [0.22–0.65]), UFH (RR = 0.36, 95% CI [0.23–0.58]), betrixaban (RR = 0.28, 95% CI [0.09–0.94]), and warfarin (RR = 0.22, 95% CI [0.14–0.35]); efficacy of edoxaban was better than that of dabigatran (RR = 0.43, 95% CI [0.28–0.65]), LMWH (RR = 0.42, 95% CI [0.28–0.63]), aspirin (RR = 0.40, 95% CI [0.24–0.68]), UFH (RR = 0.38, 95% CI [0.25–0.60]), betrixaban (RR = 0.30, 95% CI [0.09–0.99]), and warfarin (RR = 0.23, 95% CI [0.15–0.37]); efficacy of fondaparinux was better than that of dabigatran (RR = 0.57, 95% CI [0.47–0.69]), LMWH (RR = 0.56, 95% CI [0.48–0.66]), aspirin (RR = 0.54, 95% CI [0.38–0.77]), UFH (RR = 0.51, 95% CI [0.42–0.63]), and warfarin (RR = 0.31, 95% CI [0.24–0.40]); efficacy of rivaroxaban was better than that of dabigatran (RR = 0.58, 95% CI [0.49–0.69]), LMWH (RR = 0.57, 95% CI [0.50–0.65]), aspirin (RR = 0.55, 95% CI [0.39–0.77]), UFH (RR = 0.52, 95% CI [0.43–0.64]), and warfarin (RR = 0.32, 95% CI [0.25–0.40]); efficacy of darexaban was better than that of UFH (RR = 0.63, 95% CI [0.41–0.95]) and warfarin (RR = 0.38, 95% CI [0.25–0.59]); efficacy of dabigatran was better than that of warfarin (RR = 0.55, 95% CI [0.44–0.67]); efficacy of LMWH was better than that of warfarin (RR = 0.56, 95% CI [0.46–0.67]); efficacy of aspirin was better than that of warfarin (RR = 0.58, 95% CI [0.40–0.84]); and efficacy of UFH was better than that of warfarin (RR = 0.61, 95% CI [0.48–0.77]) (Fig. 3A). The P score of the anticoagulants’ efficacy for the prevention of DVT was in the following order: apixaban > edoxaban > fondaparinux > rivaroxaban > darexaban > dabigatran > LMWH > aspirin > UFH > betrixaban > warfarin (Table 5). Thirty-nine articles with 42 studies were included in the analysis of PE outcome (Table 6). There was no significant difference in head-to-head comparisons of the efficacy of the 11 anticoagulants for the prevention of PE (Fig. 3B). The P score of the anticoagulants’ efficacy for the prevention of PE was in the following order: warfarin > apixaban > aspirin > rivaroxaban > fondaparinux > edoxaban > darexaban > LMWH > dabigatran > betrixaban > UFH (Table 7). After the exclusion of individual studies one by one, the remaining studies were pooled and analyzed again. The results showed that each excluded study had a minor impact on the amount of pooling effect, indicating that the results of this meta-analysis were stable and reliable. The results of funnel plots showed that there was no publication bias for the outcome of DVT (Egger test P = .067, Begg–Mazumdar test P = .801, Thompson–Sharp test P = .296) (Fig. 4A) or PE (Egger test P = .297, Begg–Mazumdar test P = .738, Thompson–Sharp test P = .554) (Fig. 4B).

Table 2 - Result of node-splitting test for DVT.
Comparison P value
LMWH vs apixaban .676
Warfarin vs apixaban .619
Aspirin vs LMWH .443
Aspirin vs rivaroxaban .880
Fondaparinux vs LMWH .469
Fondaparinux vs UFH .716
LMWH vs rivaroxaban .174
LMWH vs UFH .615
LMWH vs warfarin .655
DVT = deep vein thrombosis, LMWH = low molecular weight heparin, UFH = unfractionated heparin.

Table 3 - Result of node-splitting test for PE.
Comparison P value
LMWH vs apixaban .579
Warfarin vs apixaban 1.000
Aspirin vs LMWH .557
Aspirin vs rivaroxaban .449
Fondaparinux vs LMWH .711
Fondaparinux vs UFH .740
LMWH vs rivaroxaban .424
LMWH vs UFH .914
LMWH vs warfarin .580
LMWH = low molecular weight heparin, PE = pulmonary embolism, UFH = unfractionated heparin.

Table 4 - Characteristics of anticoagulants’ efficacy for prevention of DVT.
Study Treatment Responder Sample size
1 LMWH 2 398
1 Aspirin 1 380
2 Rivaroxaban 3 902
2 Aspirin 2 902
3 Rivaroxaban 3 815
3 Aspirin 4 805
4 Fondaparinux 0 55
4 LMWH 1 53
5 Rivaroxaban 4 98
5 LMWH 11 98
6 Rivaroxaban 14 42
6 LMWH 10 42
7 Rivaroxaban 2 114
7 LMWH 4 114
8 Fondaparinux 45 361
8 LMWH 98 361
9 Fondaparinux 2 55
9 LMWH 1 54
10 Aspirin 1 14
10 Rivaroxaban 2 18
11 Rivaroxaban 5 60
11 LMWH 6 60
12 Dabigatran 39 297
12 LMWH 72 300
13 Rivaroxaban 2 29
13 LMWH 18 106
14 Dabigatran 181 503
14 LMWH 184 511
15 Dabigatran 1 675
15 LMWH 8 685
16 Dabigatran 40 874
16 LMWH 56 894
17 Dabigatran 6 1137
17 LMWH 1 1142
18 Rivaroxaban 6 59
18 LMWH 18 107
19 Darexaban 5 27
19 LMWH 12 31
20 Rivaroxaban 12 1595
20 LMWH 53 1558
21 Darexaban 16 120
21 LMWH 24 127
22 Dabigatran 60 791
22 LMWH 67 783
23 Dabigatran 0 1001
23 LMWH 4 992
24 Warfarin 72 122
24 LMWH 41 108
25 Edoxaban 22 299
25 LMWH 41 295
26 Darexaban 4 136
26 LMWH 2 82
27 Darexaban 11 71
27 LMWH 14 66
28 Edoxaban 6 255
28 LMWH 17 248
29 LMWH 37 166
29 Aspirin 28 120
30 LMWH 5 54
30 Rivaroxaban 4 54
31 Dabigatran 188 604
31 LMWH 163 643
32 LMWH 3 30
32 Rivaroxaban 1 30
33 LMWH 200 813
33 UFH 204 815
34 Fondaparinux 13 275
34 LMWH 18 296
35 LMWH 80 673
35 Warfarin 81 338
36 Apixaban 6 110
36 LMWH 22 110
37 Rivaroxaban 14 864
37 LMWH 71 869
38 LMWH 9 101
38 UFH 24 116
39 Rivaroxaban 24 350
39 LMWH 23 351
40 Fondaparinux 36 908
40 LMWH 83 918
41 Apixaban 5 105
41 LMWH 15 109
41 Warfarin 29 109
42 Rivaroxaban 79 824
42 LMWH 160 878
43 Rivaroxaban 0 50
43 LMWH 4 50
44 Fondaparinux 60 360
44 LMWH 59 223
44 UFH 24 72
45 Fondaparinux 17 261
45 LMWH 17 148
45 UFH 5 32
46 LMWH 1 45
46 Dabigatran 1 45
47 Rivaroxaban 3 50
47 LMWH 5 50
48 Rivaroxaban 10 48
48 LMWH 9 36
49 Rivaroxaban 8 80
49 LMWH 0 80
50 LMWH 20 144
50 Edoxaban 2 158
51 Aspirin 3 34
51 Rivaroxaban 3 36
52 LMWH 2 50
52 UFH 2 50
53 Rivaroxaban 1 50
53 LMWH 0 25
54 Fondaparinux 44 784
54 LMWH 65 796
55 Rivaroxaban 14 60
55 LMWH 31 70
56 Rivaroxaban 61 965
56 LMWH 86 959
57 Betrixaban 9 65
57 LMWH 4 40
58 Rivaroxaban 8 96
58 LMWH 17 99
59 Rivaroxaban 1 89
59 LMWH 4 89
60 Rivaroxaban 1 60
60 LMWH 3 60
61 LMWH 21 76
61 Apixaban 12 83
62 Rivaroxaban 3 15
62 LMWH 4 15
63 Rivaroxaban 4 75
63 LMWH 3 70
64 Fondaparinux 6 84
64 LMWH 5 83
65 LMWH 6 45
65 Rivaroxaban 7 45
66 LMWH 6 43
66 Rivaroxaban 1 43
67 Rivaroxaban 3 102
67 LMWH 14 112
67 Aspirin 18 110
DVT = deep vein thrombosis, LMWH = low molecular weight heparin, UFH = unfractionated heparin.

Table 5 - The P score of anticoagulants’ efficacy for prevention of DVT.
Anticoagulants P score Rank
Apixaban .940 1
Edoxaban .917 2
Fondaparinux .750 3
Rivaroxaban .731 4
Darexaban .621 5
Dabigatran .392 6
LMWH .358 7
Aspirin .310 8
UFH .233 9
Betrixaban .216 10
Warfarin .033 11
DVT = deep vein thrombosis, LMWH = low molecular weight heparin, UFH = unfractionated heparin.

Table 6 - Characteristics of anticoagulants’ efficacy for prevention of PE.
Study Treatment Responder Sample size
1 LMWH 3 398
1 Aspirin 0 380
2 Rivaroxaban 4 902
2 Aspirin 3 902
3 Rivaroxaban 4 815
3 Aspirin 4 805
4 Rivaroxaban 0 42
4 LMWH 0 42
5 Rivaroxaban 0 114
5 LMWH 0 114
6 Fondaparinux 1 517
6 LMWH 4 517
7 Rivaroxaban 0 60
7 LMWH 0 60
8 Dabigatran 0 297
8 LMWH 0 300
9 Dabigatran 0 675
9 LMWH 1 685
10 Dabigatran 5 1137
10 LMWH 3 1142
11 Rivaroxaban 0 59
11 LMWH 0 107
12 Rivaroxaban 4 1595
12 LMWH 1 1558
13 Darexaban 0 120
13 LMWH 0 127
14 Dabigatran 1 1001
14 LMWH 2 992
15 Dabigatran 1 1001
15 LMWH 2 992
16 Warfarin 0 122
16 LMWH 0 108
17 Edoxaban 0 299
17 LMWH 0 295
18 Edoxaban 0 255
18 LMWH 0 248
19 Dabigatran 6 604
19 LMWH 5 643
20 LMWH 1 813
20 UFH 1 815
21 Fondaparinux 1 277
21 LMWH 5 297
22 Rivaroxaban 1 864
22 LMWH 4 869
23 LMWH 1 125
23 UFH 2 134
24 Rivaroxaban 2 350
24 LMWH 1 351
25 Fondaparinux 2 1129
25 LMWH 2 1123
26 Apixaban 0 105
26 LMWH 2 109
26 Warfarin 0 109
27 Rivaroxaban 0 824
27 LMWH 4 878
28 Fondaparinux 1 360
28 LMWH 0 223
28 UFH 0 72
29 Fondaparinux 0 261
29 LMWH 0 148
29 UFH 0 32
30 LMWH 0 45
30 Dabigatran 0 45
31 Rivaroxaban 1 50
31 LMWH 2 50
32 Rivaroxaban 0 48
32 LMWH 0 36
33 Rivaroxaban 0 80
33 LMWH 0 80
34 LMWH 0 50
34 UFH 0 50
35 Fondaparinux 5 1126
35 LMWH 1 1128
36 Rivaroxaban 0 60
36 LMWH 0 70
37 Rivaroxaban 5 1526
37 LMWH 8 1508
38 Betrixaban 1 65
38 LMWH 0 40
39 LMWH 0 76
39 Apixaban 0 83
40 Rivaroxaban 0 15
40 LMWH 0 15
41 Fondaparinux 0 84
41 LMWH 0 83
42 Rivaroxaban 0 102
42 LMWH 0 112
42 Aspirin 0 110
LMWH = low molecular weight heparin, PE = pulmonary embolism, UFH = unfractionated heparin.

Table 7 - The P score of anticoagulants’ efficacy for prevention of PE.
Anticoagulants P score Rank
Warfarin .716 1
Apixaban .708 2
Aspirin .671 3
Rivaroxaban .580 4
Fondaparinux .545 5
Edoxaban .461 6
Darexaban .455 7
LMWH .400 8
Dabigatran .395 9
Betrixaban .325 10
UFH .244 11
LMWH = low molecular weight heparin, PE = pulmonary embolism, UFH = unfractionated heparin.

F2
Figure 2.:
Network plots of overall efficacy. (A) DVT outcome. (B) PE outcome. The width of the lines is proportional to the number of trials comparing every pair of treatments, and the size of every node is proportional to the number of participants. DVT = deep vein thrombosis, PE = pulmonary embolism.
F3
Figure 3.:
League tables of results. (A) DVT outcome. (B) PE outcome. Results of the network meta-analysis are presented in the left lower half and results from pairwise meta-analysis in the upper right half, if available. DVT = deep vein thrombosis, PE = pulmonary embolism.
F4
Figure 4.:
Funnel plots of results. (A) DVT outcome. (B) PE outcome. DVT = deep vein thrombosis, PE = pulmonary embolism.

5.3. Grading the evidence of the network meta-analysis using CINeMA

After the assessment of 6 domains by CINeMA (Table S1, Supplemental Digital Content, https://links.lww.com/MD/I302; Table S2, Supplemental Digital Content, https://links.lww.com/MD/I303; Table S3, Supplemental Digital Content, https://links.lww.com/MD/I304; Table S4, Supplemental Digital Content, https://links.lww.com/MD/I305; Table S5, Supplemental Digital Content, https://links.lww.com/MD/I306; and Table S6, Supplemental Digital Content, https://links.lww.com/MD/I307), every included study’s confidence rating was assigned as follows: high = 0; moderate = −1; low = −2; very low ≤ −3. The entire confidence in evidence was obtained by the weighted average algorithm of confidence rating of every included study. The entire confidence in the evidence of anticoagulants for the prevention of VTE was low.

6. Discussion

VTE is a frequent and increasing disease, which is associated with severe venous disease and high treatment costs.[70] The main reason for the occurrence of VTE is that after joint replacement, the human body is in a hypercoagulable state, where the coagulation mechanism is activated, procoagulant substances such as thromboxane and fibrinogen increase, and inflammation and edema of the surgical site tissue compress the blood vessels, resulting in slow local blood flow.[71] Therefore, to prevent the occurrence of VTE after THA or TKA, it is not enough to only rely on bed rest, use of pneumatic compression, wearing compression stockings, and other general measures; systematic anticoagulant therapy must be given.

In this study, we reviewed the efficacy of 11 anticoagulants in patients undergoing THA or TKA. Evidence was compiled from direct and indirect comparisons to evaluate the efficacy. For the prevention of DVT, the results of the league table and P score showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for patients undergoing THA or TKA. Due to the relatively low incidence of PE, the results of the league table and P score showed that there was no difference in the efficacy among the anticoagulants for the prevention of PE. All these effective anticoagulants belong to new oral anticoagulants (NOACs) (apixaban, edoxaban, rivaroxaban, and darexaban). NOACs represent novel direct-acting medications that directly inhibit factor Xa or factor IIa.[72] These drugs have been approved for the prevention of VTE in patients after elective hip or knee arthroplasty in the European Union and many other countries worldwide.[73] Compared with other traditional anticoagulants, NOACs have various advantages, such as the absence of food interactions, few strong drug interactions, predictable pharmacokinetics and pharmacodynamics, rapid onset and offset of action, and absence of the need for laboratory monitoring.[74,75] However, NOACs have disadvantages, such as contraindication or dose reduction in patients with chronic kidney disease or hepatic disease, absence of a specific test, the potential for overuse, lack of a specific antidote in case of major bleeding, and high costs.[74,75]

At the same time, the short half-lives of NOACs can be considered both an advantage and a disadvantage under various circumstances. For example, the advantage of the short half-life of an NOAC may be relevant for emergency surgery and in cases of bleeding due to accumulation of the drug in the blood, whereas the short half-life is a disadvantage if the patient forgets to take the drug, which could put the patient at risk[74]; therefore, many traditional anticoagulants can be replaced. This study showed that fondaparinux had a high efficacy for the prevention of DVT. Fondaparinux, a synthetic pentasaccharide, is the first drug in a new class of antithrombotic agents – selective factor Xa inhibitors.[76] Fondaparinux is completely absorbed following subcutaneous injection, and its activity is higher than that of LMWH (about 700 units/mg and 100 units/mg, respectively).[77] The half-life of fondaparinux is 17 hours, so it is suitable for daily dosing.[78] Fondaparinux undergoes renal clearance and therefore requires dose reduction or replacement in patients with poor renal function.[77]

This article had some limitations. First, studies in languages other than English and Chinese were excluded, which may have affected the comprehensiveness of the included studies. Second, the entire confidence in the collected evidence as assessed by CINeMA was low, so the results should be interpreted with caution.

7. Conclusion

In this study, we provided a useful reference for the selection of anticoagulants for the prevention of VTE after THA or TKA. Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban showed the best efficacy. However, more high-quality studies are needed to confirm the above conclusions.

Author contributions

Conceptualization: Zhihao Huang, Xinru Xu, Dan Xu.

Formal analysis: Zhihao Huang, Xinru Xu, Miao Zou.

Investigation: Xinru Xu.

Methodology: Zhihao Huang, Pengfei Zhao.

Project administration: Zhihao Huang.

Software: Zhihao Huang.

Supervision: Zhihao Huang, Xinru Xu.

Visualization: Xinru Xu, Dan Xu.

Writing – original draft: Zhihao Huang, Xinru Xu.

Writing – review and editing: Zhihao Huang, Xinru Xu, Dan Xu, Pengfei Zhao, Miao Zou.

Abbreviations:

CI =
confidence interval
CINeMA =
Confidence in Network Meta-Analysis
DVT =
deep vein thrombosis
LMWH =
low molecular weight heparin
NOAC =
anticoagulants belong to new oral anticoagulant
PE =
pulmonary embolism
RR =
relative risk
THA =
total hip arthroplasy
TKA =
total knee arthroplasty
UFH =
unfractionated heparin
VTE =
venous thromboembolism

References

[1]. Martinez C, Cohen AT, Bamber L, et al. Epidemiology of first and recurrent venous thromboembolism: a population-based cohort study in patients without active cancer. Thromb Haemost. 2014;112:255–63.
[2]. Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388:3060–73.
[3]. Raskob GE, Angchaisuksiri P, Blanco AN, et al. Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol. 2014;34:2363–71.
[4]. Eriksson H. Treatment of venous thromboembolism and long-term prevention of recurrence: present treatment options and ximelagatran. Drugs. 2004;64:37–46.
[5]. Beyer-Westendorf J, Cohen AT, Monreal M. Venous thromboembolism prevention and treatment: expanding the rivaroxaban knowledge base with real-life data. Eur Heart J Suppl. 2015;17:D32–41.
[6]. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
[7]. Nikolakopoulou A, Higgins JPT, Papakonstantinou T, et al. CINeMA: An approach for assessing confidence in the results of a network meta-analysis. PLoS Med. 2020;17:e1003082.
[8]. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.
[9]. Anderson DR, Dunbar MJ, Bohm ER, et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013;158:800–6.
[10]. Anderson DR, Dunbar M, Murnaghan J, et al. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018;378:699–707.
[11]. Argun M, Oner M, Saglamoglu M, et al. Fondaparinux versus nadroparin for prevention of venous thromboembolism after elective hip and knee arthroplasty. Curr Ther Res Clin Exp. 2013;74:49–53.
[12]. Bai Y, Fang T, Sun R. Rivaroxaban and low molecular heparin in prevention of deep venous thrombosis and blood loss after total hip arthroplasty in eldeYZy patients. J Clin Rehabil Tis Eng Res. 2018;22:2303–8.
[13]. Bai Z, Shen H, An S. Effect and complications of rivaroxaban in preventing deep venous thrombosis after total knee arthroplasty. Chin J Joint Surg (Electronic Edition). 2020;14:572–7.
[14]. Bai CW, Ruan RX, Pan S, et al. Application of thromboelastography in comparing coagulation difference of rivaroxaban and enoxaparin for thromboprophylaxis after total hip arthroplasty. J Orthop Surg (Hong Kong). 2021;29:23094990211042674.
[15]. Bauer KA, Eriksson BI, Lassen MR, et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001;345:1305–10.
[16]. Bonneux IM, Bellemans J, Fabry G. Evaluation of wound healing after total knee arthroplasty in a randomized prospective trial comparing fondaparinux with enoxaparin. Knee. 2006;13:118–21.
[17]. Colleoni JL, Ribeiro FN, Mos PAC, et al. Venous thromboembolism prophylaxis after total knee arthroplasty (TKA): aspirin vs. rivaroxaban. Rev Bras Ortop. 2017;53:22–7.
[18]. Ding H, He Y, Chen Y. Efficacy and safety of applying rivaroxaban to prevent deep venous thrombosis in patients underwent hip arthroplasty. Hainan Med J. 2014;25:1916–8.
[19]. Eriksson BI, Dahl OE, Büller HR, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005;3:103–11.
[20]. Eriksson BI, Borris L, Dahl OE, et al. Oral, direct factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost. 2006;4:121–8.
[21]. Eriksson BI, Dahl OE, Rosencher N, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007;5:2178–85.
[22]. Eriksson BI, Dahl OE, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56.
[23]. Eriksson BI, Borris LC, Dahl OE, et al. Dose-escalation study of rivaroxaban (BAY 59-7939) – an oral, direct factor Xa inhibitor – for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Res. 2007;120:685–93.
[24]. Eriksson BI, Turpie AG, Lassen MR, et al. A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgery. J Thromb Haemost. 2007;5:1660–5.
[25]. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765–75.
[26]. Eriksson BI, Turpie AG, Lassen MR, et al. Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2). J Thromb Haemost. 2010;8:714–21.
[27]. Eriksson BI, Dahl OE, Huo MH, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost. 2011;105:721–9.
[28]. Fitzgerald RH Jr, Spiro TE, Trowbridge AA, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg Am. 2001;83:900–6.
[29]. Fuji T, Wang CJ, Fujita S, et al. Safety and efficacy of edoxaban, an oral factor Xa inhibitor, versus enoxaparin for thromboprophylaxis after total knee arthroplasty: the STARS E-3 trial. Thromb Res. 2014;134:1198–204.
[30]. Fuji T, Nakamura M, Takeuchi M. Darexaban for the prevention of venous thromboembolism in Asian patients undergoing orthopedic surgery: results from 2 randomized, placebo-controlled, double-blind studies. Clin Appl Thromb Hemost. 2014;20:199–211.
[31]. Fuji T, Fujita S, Kawai Y, et al. Efficacy and safety of edoxaban versus enoxaparin for the prevention of venous thromboembolism following total hip arthroplasty: STARS J-V. Thromb J. 2015;13:27.
[32]. Gao F, Li Z, Zhang K, et al. Impact of low molecular weight heparin on hidden blood loss and blood transfusion rate after primary total knee arthroplasty. Chin J Repar Reconstr Surg. 2011;25:393–96.
[33]. Gao S. Effect analysis of rivaroxaban applied on patients with hip replacement to prevent deep venous thrombosis after treatment. Clin Med Chin. 2016;32:1112–4.
[34]. Ginsberg JS, Davidson BL, Comp PC, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009;24:1–9.
[35]. Guo S, Wu C, Wei Q. Prevention of deep vein thrombosis after total joint replacement by rivaroxaban. Pharm J Chin PLA. 2018;34:377–9.
[36]. Haas S, Breyer HG, Bacher HP, et al. Prevention of major venous thromboembolism following total hip or knee replacement: a randomized comparison of low-molecular-weight heparin with unfractionated heparin (ECHOS Trial). Int Angiol. 2006;25:335–42.
[37]. Hosaka K, Saito S, Ishii T, et al. Safety of fondaparinux versus enoxaparin after TKA in Japanese patients. Orthopedics. 2013;36:e428–33.
[38]. Hull RD, Pineo GF, Francis C, et al. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. Arch Intern Med. 2000;160:2199–207.
[39]. Jiang H, Meng J, Guo T, et al. Comparison of apixaban and low molecular weight heparin in preventing deep venous thrombosis after total knee arthroplasty in older adults. Yonsei Med J. 2019;60:626–32.
[40]. Kakkar VV, Howes J, Sharma V, et al. A comparative double-blind, randomised trial of a new second generation LMWH (bemiparin) and UFH in the prevention of post-operative venous thromboembolism. The Bemiparin Assessment group. Thromb Haemost. 2000;83:523–9.
[41]. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372:31–9.
[42]. Kim SM, Moon YW, Lim SJ, et al. Effect of oral factor Xa inhibitor and low-molecular-weight heparin on surgical complications following total hip arthroplasty. Thromb Haemost. 2016;115:600–7.
[43]. Lassen MR, Bauer KA, Eriksson BI, et al. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002;359:1715–20.
[44]. Lassen MR, Davidson BL, Gallus A, et al. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost. 2007;5:2368–75.
[45]. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776–86.
[46]. Li X, Mao L, Lin M, et al. Effect comparison between rivaroxaban and low molecular weight heparin in the prevention of deep venous thrombosis after hip and knee joint arthroplasty. J Bengbu Med Coll. 2018;43:1565–8.
[47]. Migita K, Bito S, Nakamura M, et al. Venous thromboembolism after total joint arthroplasty: results from a Japanese multicenter cohort study. Arthritis Res Ther. 2014;16:R154.
[48]. Mirdamadi A, Dashtkar S, Kaji M, et al. Dabigatran versus Enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized clinical trial. ARYA Atheroscler. 2014;10:292–7.
[49]. Qin C, Zhang L, Zhang Z, et al. Comparison of the effects of different methods on prevention of venous thromboembolism in patients after total hip replacement. Chin J Vasc Surg (Electronic Version). 2016;18:299–302.
[50]. Quan D, Zhu J, Wang H, et al. Rivaroxaban versus low molecular weight heparin in prevention of venous thromboembolism in patients undergoing hip or knee arthroplasty. Chin J Onhop Trauma. 2010;12:1130–4.
[51]. Rahman WA, Habsa GH, Al-Mohrej OA, et al. Incidence of silent venous thromboembolism after total hip arthroplasty: a comparison of rivaroxaban and enoxaparin. J Orthop Surg (Hong Kong). 2020;28:2309499020938865.
[52]. Raskob G, Cohen AT, Eriksson BI, et al. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study. Thromb Haemost. 2010;104:642–9.
[53]. Ren Y, Cao SL, Li Z, et al. Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty: a randomized controlled trial. Chin Med J (Engl). 2021;134:164–72.
[54]. Senaran H, Acaroğlu E, Özdemir HM, et al. Enoxaparin and heparin comparison of deep vein thrombosis prophylaxis in total hip replacement patients. Arch Orthop Trauma Surg. 2006;126:1–5.
[55]. Shi Z, Yan G, Xiao J, et al. Clinical investigation on rivaroxaban for thromboprophylaxis after total knee arthroplasty. Chin J Joint Surg (Electronic Edition). 2014;8:713–7.
[56]. Turpie AG, Bauer KA, Eriksson BI, et al. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. 2002;359:1721–6.
[57]. Turpie AG, Fisher WD, Bauer KA, et al. BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. J Thromb Haemost. 2005;3:2479–86.
[58]. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373:1673–80.
[59]. Turpie AG, Bauer KA, Davidson BL, et al. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost. 2009;101:68–76.
[60]. Wang P. Research of rivaroxaban versus low molecular weight heparin to prevent deep venous thrombosis following total knee arthroplasty. Chin J Front Med Sci (Electronic Version). 2014;6:111–4.
[61]. Wang C, Wang Y, Zhou D, et al. Randomized controlled trial of oral rivaroxaban for deep vein thrombosis prophylaxis in eldeYZy patients undergoing total knee arthroplasty. Chin J Joint Surg (Electronic Edition). 2013;7:336–49.
[62]. Wang X, Tao H, Wei S, et al. Role of rivaroxaban in preventing deep venous thrombosis of lower limbs after total hip replacement. Chin J Clin Pharmacol. 2020;36:2620–3.
[63]. Weitz JI, Bauersachs R, Becker B, et al. Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty: The FOXTROT randomized clinical trial. JAMA. 2020;323:130–9.
[64]. Wu G, Li G, Dai B, et al. The effectiveness and safety of rivaroxaban versus low molecular weight heparin calcium on preventing postoperative lower extremity deep vein thrombosis in eldeYZy patients with hip fracture. Chin J Clin Res. 2013;26:5–7.
[65]. Yang L, Wang C, Shen T, et al. Clinical study of deep venous thrombosis prevention after total hip arthroplasty with oral rivaroxaban. Chin J Clin Pharmacol. 2013;29:260–2.
[66]. Yokote R, Matsubara M, Hirasawa N, et al. Is routine chemical thromboprophylaxis after total hip replacement really necessary in a Japanese population? J Bone Joint Surg Br. 2011;93:251–6.
[67]. Zhang J, Du G, Liu W, et al. Comparison of the effects between injection of low molecular weight heparin and oral rivaroxiban in preventing deep venous thrombosis in patients undergoing total hip replacement. Chin J Thromb Hemost. 2017;23:756–8.
[68]. Zhang C, Song G, Liu Z, et al. Comparative analysis of the efficacy and safety of low molecular weight heparin and rivaroxaban in prevention of venous thrombosis after TKA. Shaanxi Med J. 2020;49:1153–6.
[69]. Zou Y, Tian S, Wang Y, et al. Administering aspirin, rivaroxaban and low-molecular-weight heparin to prevent deep venous thrombosis after total knee arthroplasty. Blood Coagul Fibrinolysis. 2014;25:660–4.
[70]. Akin M, Schäfer A, Akin I, et al. Use of new oral anticoagulants in the treatment of venous thromboembolism and thrombotic prophylaxis. Cardiovasc Hematol Disord Drug Targets. 2015;15:92–6.
[71]. Zhang H, Ding C, Lv C, et al. Effect of drugs in the prevention of venous thromboembolism after arthroplasty: a network meta- analysis. J Qingdao Univ (Med Sci). 2020;56:51–5.
[72]. Scaglione F. New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013;52:69–82.
[73]. Klauser W, Dütsch M. Practical management of new oral anticoagulants after total hip or total knee arthroplasty. Musculoskelet Surg. 2013;97:189–97.
[74]. Mekaj YH, Mekaj AY, Duci SB, et al. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag. 2015;11:967–77.
[75]. Bauer KA. Pros and cons of new oral anticoagulants. Hematol Am Soc Hematol Educ Program. 2013;2013:464–70.
[76]. Petitou M, Duchaussoy P, Herbert JM, et al. The synthetic pentasaccharide fondaparinux: first in the class of antithrombotic agents that selectively inhibit coagulation factor Xa. Semin Thromb Hemost. 2002;28:393–402.
[77]. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e24S–43S.
[78]. Hepponstall M, Chan A, Monagle P. Anticoagulation therapy in neonates, children and adolescents. Blood Cells Mol Dis. 2017;67:41–7.
Keywords:

anticoagulants; deep vein thrombosis (DVT); network meta-analysis; pulmonary embolism (PE); total hip arthroplasty; total knee arthroplasty (TKA); venous thromboembolism (VTE)

Supplemental Digital Content

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.