Efficacy and safety of new oral anticoagulants for patients undergoing joint replacement: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

LING Tao ^1,2 , XU Ruijuan ² ,  WANG Bin ^3,4 ,  GE Weihong ²

1. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R.China;
2. Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing 210008, P.R.China;
3. Department of Orthopaedics, Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R.China;
4. Department of Sports Medicine and Adult Reconstruction Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210009, P.R.China;

Corresponding author：

WANG Bin, Email: wangbin_pku@163.com; GE Weihong, Email: 6221230@sina.com

Keywords：

Venous thromboembolism; New oral anticoagulant; Enoxaparin; Joint arthroplasty; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.202002020

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objectives To systematically review the efficacy and safety of new oral anticoagulants (Apixaban, Rivaroxaban, or Dabigatran) after joint replacement.Methods CNKI, WanFang Data, VIP, CBM, PubMed, EMbase and The Cochrane Library databases were electronically searched to collect randomized controlled trials (RCTs) on new oral anticoagulants after joint replacement from inception to October, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, and then meta-analysis was performed by using RevMan 5.3 software.Results A total of 13 RCTs were included. The results of meta-analysis showed that compared to Enoxaparin, the new oral anticoagulant significantly reduced the incidence of asymptomatic deep vein thrombosis (DVT) (RR=0.60, 95%CI 0.46 to 0.78, P<0.000 1) and symptomatic DVT (RR=0.40, 95%CI 0.28 to 0.58, P<0.000 1), while the incidence of symptomatic pulmonary embolism (PE) during treatment (RR=0.91, 95%CI 0.59 to 1.39, P=0.65) and mortality (RR=1.00, 95%CI 0.40 to 1.76, P=0.99) were not reduced. Major bleeding (RR=1.05, 95%CI 0.81 to 1.35, P=0.72) and clinically relevant non-major bleeding events (RR=0.99, 95%CI 0.73 to 1.33, P=0.94) with new oral anticoagulants were not statistically different from Enoxaparin.Conclusions Current evidence shows that new oral anticoagulants can effectively reduce the incidence of DVT in patients after joint replacement without increasing the risk of adverse events such as bleeding. Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions.

Citation： LING Tao, XU Ruijuan, WANG Bin, GE Weihong. Efficacy and safety of new oral anticoagulants for patients undergoing joint replacement: a systematic review. Chinese Journal of Evidence-Based Medicine, 2020, 20(9): 1038-1044. doi: 10.7507/1672-2531.202002020 Copy

1.	Memtsoudis SG, Pumberger M, Ma Y, <italic>et al</italic>. Epidemiology and risk factors for perioperative mortality after total hip and knee arthroplasty. J Orthop Res, 2012, 30(11): 1811-1821.
2.	Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg, 2011, 19(12): 777-778.
3.	中华医学会骨科学分会. 中国骨科大手术静脉血栓栓塞症预防指南. 中华关节外科杂志(电子版), 2009, 36(3): 65-71.
4.	梁平, 李胜利. 膝骨性关节炎的临床治疗进展. 中国中医骨伤科杂志, 2006, 14(3): 65-67.
5.	Cohen AT, Asia-Pacific Thrombosis Advisory Board. Asia-Pacific Thrombosis Advisory Board consensus paper on prevention of venous thromboembolism after major orthopaedic surgery. Thromb Haemost, 2010, 104(5): 919-930.
6.	Schulman S, Kakkar AK, Goldhaber SZ, <italic>et al</italic>. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation, 2014, 129(7): 764-772.
7.	Harder S. Pharmacokinetic and pharmacodynamic evaluation of rivaroxaban: considerations for the treatment of venous thromboembolism. Thromb J, 2014, 12: 22.
8.	Eriksson BI, Borris LC, Dahl OE, <italic>et al</italic>. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation, 2006, 114(22): 2374-2381.
9.	Eriksson BI, Borris LC, Friedman RJ, <italic>et al</italic>. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med, 2008, 358(26): 2765-2775.
10.	Kakkar AK, Brenner B, Dahl OE, <italic>et al</italic>. 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(9632): 31-39.
11.	Lassen MR, Ageno W, Borris LC, <italic>et al</italic>. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med, 2008, 358(26): 2776-2786.
12.	Turpie AG, Lassen MR, Davidson BL, <italic>et al</italic>. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet, 2009, 373(9676): 1673-1680.
13.	Lassen MR, Davidson BL, Gallus A, <italic>et al</italic>. 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(12): 2368-2375.
14.	Lassen MR, Raskob GE, Gallus A, <italic>et al</italic>. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med, 2009, 361(6): 594-604.
15.	Lassen MR, Raskob GE, Gallus A, <italic>et al</italic>. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomized double-blind trial. Lancet, 2010, 375(9717): 807-815.
16.	Lassen MR, Gallus A, Raskob GE, <italic>et al</italic>. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med, 2010, 363(26): 2487-2498.
17.	Eriksson BI, Dahl OE, Rosencher N, <italic>et al</italic>. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomizedtrial. J Thromb Haemost, 2007, 5(11): 2178-2185.
18.	Eriksson BI, Dahl OE, Rosencher N, <italic>et al</italic>. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. Lancet, 2007, 370(9591): 949-956.
19.	RE-MOBILIZE Writing Committee, Ginsberg JS, Davidson BL, <italic>et al</italic>. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty, 2009, 24(1): 1-9.
20.	Eriksson BI, Dahl OE, Huo MH, <italic>et al</italic>. 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(4): 721-729.
21.	吴俊, 李广翼, 陈云苏, 等. 三种氨甲环酸联合用药方案在初次人工全膝关节置换术中的疗效比较. 中国修复重建外科杂志, 2018, 32(11): 1397-1401.
22.	李军, 荆珏华, 周云,等. 利伐沙班和依诺肝素钠对人工全膝关节置换术后失血风险的影响比较. 中国修复重建外科杂志, 2014, 28(1): 26-29.
23.	王国栋, 张元民, 赵晓伟, 等. 利伐沙班对初次行人工全膝关节置换术后隐性失血及输血率的影响. 中国修复重建外科杂志, 2012, 26(11): 1306-1309.
24.	Raskob G, Cohen AT, Eriksson BI, <italic>et al</italic>. 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(3): 642-649.
25.	Ma G, Zhang R, Wu X, <italic>et al</italic>. 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. Thromb Res, 2015, 135(5): 816-822.
26.	Hebbeler SL, Marciniak CM, Crandall S, <italic>et al</italic>. Daily vs twice daily enoxaparin in the prevention of venous thromboembolic disorders during rehabilitation following acute spinal cord injury. J Spinal Cord Med, 2004, 27(3): 236-240.
27.	Trkulja V, Kolundzic R. Rivaroxaban vs dabigatran for thromboprophylaxis after joint-replacement surgery: exploratory indirect comparison based on meta-analysis of pivotal clinical trials. Croat Med J, 2010, 51(2): 113-123.
28.	Maratea D, Fadda V, Trippoli S, <italic>et al</italic>. Prevention of venous thromboembolism after major orthopedic surgery: indirect comparison of three new oral anticoagulants. J Thromb Haemost, 2011, 9(9): 1868-1870.
29.	Loke YK, Kwok CS. Dabigatran and rivaroxaban for prevention of venous thromboembolism-systematic review and adjusted indirect comparison. J Clin Pharm Ther, 2011, 36(1): 111-124.
30.	Gómez-Outes A, Terceira-Fernandez AI, Suarez-Gea ML, <italic>et al</italic>. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: a systematic review, meta-analysis, and indirect treatment comparisons. BMJ, 2012, 7863(344): e3675.
31.	刘从威, 万晓, 黎志宏, 等. 骨科大手术中的静脉血栓的预防: 口服抗凝药的系统回顾和间接比较. 临床药物治疗杂志, 2015, 13(3): 39-46.
32.	赵紫楠, 孙雪林, 胡欣, 等. 直接口服抗凝药预防骨科大手术后静脉血栓栓塞症疗效与安全性的系统评价. 中国循证医学杂志, 2019, 19(10): 1217-1225.
33.	周红娟, 喻澜, 尤春景. 无症状性下肢静脉血栓形成临床报道1例. 中华物理医学与康复杂志, 2013, 35(1): 78.

1. Memtsoudis SG, Pumberger M, Ma Y, <italic>et al</italic>. Epidemiology and risk factors for perioperative mortality after total hip and knee arthroplasty. J Orthop Res, 2012, 30(11): 1811-1821.
2. Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg, 2011, 19(12): 777-778.
3. 中华医学会骨科学分会. 中国骨科大手术静脉血栓栓塞症预防指南. 中华关节外科杂志(电子版), 2009, 36(3): 65-71.
4. 梁平, 李胜利. 膝骨性关节炎的临床治疗进展. 中国中医骨伤科杂志, 2006, 14(3): 65-67.
5. Cohen AT, Asia-Pacific Thrombosis Advisory Board. Asia-Pacific Thrombosis Advisory Board consensus paper on prevention of venous thromboembolism after major orthopaedic surgery. Thromb Haemost, 2010, 104(5): 919-930.
6. Schulman S, Kakkar AK, Goldhaber SZ, <italic>et al</italic>. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation, 2014, 129(7): 764-772.
7. Harder S. Pharmacokinetic and pharmacodynamic evaluation of rivaroxaban: considerations for the treatment of venous thromboembolism. Thromb J, 2014, 12: 22.
8. Eriksson BI, Borris LC, Dahl OE, <italic>et al</italic>. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation, 2006, 114(22): 2374-2381.
9. Eriksson BI, Borris LC, Friedman RJ, <italic>et al</italic>. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med, 2008, 358(26): 2765-2775.
10. Kakkar AK, Brenner B, Dahl OE, <italic>et al</italic>. 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(9632): 31-39.
11. Lassen MR, Ageno W, Borris LC, <italic>et al</italic>. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med, 2008, 358(26): 2776-2786.
12. Turpie AG, Lassen MR, Davidson BL, <italic>et al</italic>. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet, 2009, 373(9676): 1673-1680.
13. Lassen MR, Davidson BL, Gallus A, <italic>et al</italic>. 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(12): 2368-2375.
14. Lassen MR, Raskob GE, Gallus A, <italic>et al</italic>. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med, 2009, 361(6): 594-604.
15. Lassen MR, Raskob GE, Gallus A, <italic>et al</italic>. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomized double-blind trial. Lancet, 2010, 375(9717): 807-815.
16. Lassen MR, Gallus A, Raskob GE, <italic>et al</italic>. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med, 2010, 363(26): 2487-2498.
17. Eriksson BI, Dahl OE, Rosencher N, <italic>et al</italic>. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomizedtrial. J Thromb Haemost, 2007, 5(11): 2178-2185.
18. Eriksson BI, Dahl OE, Rosencher N, <italic>et al</italic>. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. Lancet, 2007, 370(9591): 949-956.
19. RE-MOBILIZE Writing Committee, Ginsberg JS, Davidson BL, <italic>et al</italic>. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty, 2009, 24(1): 1-9.
20. Eriksson BI, Dahl OE, Huo MH, <italic>et al</italic>. 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(4): 721-729.
21. 吴俊, 李广翼, 陈云苏, 等. 三种氨甲环酸联合用药方案在初次人工全膝关节置换术中的疗效比较. 中国修复重建外科杂志, 2018, 32(11): 1397-1401.
22. 李军, 荆珏华, 周云,等. 利伐沙班和依诺肝素钠对人工全膝关节置换术后失血风险的影响比较. 中国修复重建外科杂志, 2014, 28(1): 26-29.
23. 王国栋, 张元民, 赵晓伟, 等. 利伐沙班对初次行人工全膝关节置换术后隐性失血及输血率的影响. 中国修复重建外科杂志, 2012, 26(11): 1306-1309.
24. Raskob G, Cohen AT, Eriksson BI, <italic>et al</italic>. 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(3): 642-649.
25. Ma G, Zhang R, Wu X, <italic>et al</italic>. 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. Thromb Res, 2015, 135(5): 816-822.
26. Hebbeler SL, Marciniak CM, Crandall S, <italic>et al</italic>. Daily vs twice daily enoxaparin in the prevention of venous thromboembolic disorders during rehabilitation following acute spinal cord injury. J Spinal Cord Med, 2004, 27(3): 236-240.
27. Trkulja V, Kolundzic R. Rivaroxaban vs dabigatran for thromboprophylaxis after joint-replacement surgery: exploratory indirect comparison based on meta-analysis of pivotal clinical trials. Croat Med J, 2010, 51(2): 113-123.
28. Maratea D, Fadda V, Trippoli S, <italic>et al</italic>. Prevention of venous thromboembolism after major orthopedic surgery: indirect comparison of three new oral anticoagulants. J Thromb Haemost, 2011, 9(9): 1868-1870.
29. Loke YK, Kwok CS. Dabigatran and rivaroxaban for prevention of venous thromboembolism-systematic review and adjusted indirect comparison. J Clin Pharm Ther, 2011, 36(1): 111-124.
30. Gómez-Outes A, Terceira-Fernandez AI, Suarez-Gea ML, <italic>et al</italic>. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: a systematic review, meta-analysis, and indirect treatment comparisons. BMJ, 2012, 7863(344): e3675.
31. 刘从威, 万晓, 黎志宏, 等. 骨科大手术中的静脉血栓的预防: 口服抗凝药的系统回顾和间接比较. 临床药物治疗杂志, 2015, 13(3): 39-46.
32. 赵紫楠, 孙雪林, 胡欣, 等. 直接口服抗凝药预防骨科大手术后静脉血栓栓塞症疗效与安全性的系统评价. 中国循证医学杂志, 2019, 19(10): 1217-1225.
33. 周红娟, 喻澜, 尤春景. 无症状性下肢静脉血栓形成临床报道1例. 中华物理医学与康复杂志, 2013, 35(1): 78.

Previous Article
Pharmacoeconomic evaluation models for hepatitis C therapies: a systematic review
Next Article
The correlation between serum selenium levels in pregnant females and preterm birth: a meta-analysis

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of new oral anticoagulants for patients undergoing joint replacement: a systematic review

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content