Direct factor Xa inhibitors (rivaroxaban and apixaban) versus enoxaparin for the prevention of venous thromboembolism after total knee replacement: A meta-analysis of 6 randomized clinical trials.
OBJECTIVE
A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and safety of direct factor Xa inhibitors (rivaroxaban and apixaban) with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee replacement.


METHODS
A systematic literature search in Medline, EMBASE, EBSCO, Springer, Ovid and Cochrane library databases was performed to identify RCTs comparing rivaroxaban/apixaban with enoxaparin for the prevention of VTE after total knee replacement. The outcomes including deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding were pooled using risk ratios (RRs) with their 95% confidence intervals (95% CIs) as statistic.


RESULTS
A total of 6 RCTs with 13,790 patients were included in this meta-analysis. Overall, the incidence of DVT was significantly decreased with the use of direct Xa inhibitors (both twice daily [b.i.d] and once daily [q.d.] regimes) comparing with the enoxaparin treatment (P<0.01); however, there was no significant influencing difference between direct Xa inhibitors (b.i.d. regime) and enoxaparin on the incidence of PE (P=0.06), while significantly lower rate was found for q.d. regime of direct Xa inhibitors (P=0.02). With respect to major bleeding, the pooled analysis did not demonstrate a significant difference between direct Xa inhibitors (b.i.d. and q.d. regimes) and enoxaparin (30mg and 40mg b.i.d.).


CONCLUSIONS
In conclusion, our results confirmed that direct Xa inhibitors (rivaroxaban and apixaban) were more effective for prevention of VTE after total knee replacement as compared with enoxaparin, without increasing major bleeding risk.
Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310020, China.
Guofeng
G
Ma
Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310020, China.
Ruifeng
R
Zhang
Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310020, China.
Xiaohong
X
Wu
Radiology Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China, 310020.
Dan
D
Wang
Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310020, China. Electronic address: ycouldj@163.com.
Kejing
K
Ying
D000925:Anticoagulants / Q000627:therapeutic use; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D017984:Enoxaparin / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D011655:Pulmonary Embolism / Q000150:complications / Q000517:prevention & control; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069552:Rivaroxaban / Q000627:therapeutic use*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications* / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000150:complications / Q000517:prevention & control
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban
Apixaban; Enoxaparin; Factor Xa inhibitor; Rivaroxaban; Total knee replacement; Venous thromboembolism