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：

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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.	中華醫學會骨科學分會. 中國骨科大手術靜脈血栓栓塞癥預防指南. 中華關節外科雜志(電子版), 2009, 36(3): 65-71.
4.	梁平, 李勝利. 膝骨性關節炎的臨床治療進展. 中國中醫骨傷科雜志, 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.	吳俊, 李廣翼, 陳云蘇, 等. 三種氨甲環酸聯合用藥方案在初次人工全膝關節置換術中的療效比較. 中國修復重建外科雜志, 2018, 32(11): 1397-1401.
22.	李軍, 荊玨華, 周云,等. 利伐沙班和依諾肝素鈉對人工全膝關節置換術后失血風險的影響比較. 中國修復重建外科雜志, 2014, 28(1): 26-29.
23.	王國棟, 張元民, 趙曉偉, 等. 利伐沙班對初次行人工全膝關節置換術后隱性失血及輸血率的影響. 中國修復重建外科雜志, 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.	劉從威, 萬曉, 黎志宏, 等. 骨科大手術中的靜脈血栓的預防: 口服抗凝藥的系統回顧和間接比較. 臨床藥物治療雜志, 2015, 13(3): 39-46.
32.	趙紫楠, 孫雪林, 胡欣, 等. 直接口服抗凝藥預防骨科大手術后靜脈血栓栓塞癥療效與安全性的系統評價. 中國循證醫學雜志, 2019, 19(10): 1217-1225.
33.	周紅娟, 喻瀾, 尤春景. 無癥狀性下肢靜脈血栓形成臨床報道1例. 中華物理醫學與康復雜志, 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. 中華醫學會骨科學分會. 中國骨科大手術靜脈血栓栓塞癥預防指南. 中華關節外科雜志(電子版), 2009, 36(3): 65-71.
4. 梁平, 李勝利. 膝骨性關節炎的臨床治療進展. 中國中醫骨傷科雜志, 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. 吳俊, 李廣翼, 陳云蘇, 等. 三種氨甲環酸聯合用藥方案在初次人工全膝關節置換術中的療效比較. 中國修復重建外科雜志, 2018, 32(11): 1397-1401.
22. 李軍, 荊玨華, 周云,等. 利伐沙班和依諾肝素鈉對人工全膝關節置換術后失血風險的影響比較. 中國修復重建外科雜志, 2014, 28(1): 26-29.
23. 王國棟, 張元民, 趙曉偉, 等. 利伐沙班對初次行人工全膝關節置換術后隱性失血及輸血率的影響. 中國修復重建外科雜志, 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. 劉從威, 萬曉, 黎志宏, 等. 骨科大手術中的靜脈血栓的預防: 口服抗凝藥的系統回顧和間接比較. 臨床藥物治療雜志, 2015, 13(3): 39-46.
32. 趙紫楠, 孫雪林, 胡欣, 等. 直接口服抗凝藥預防骨科大手術后靜脈血栓栓塞癥療效與安全性的系統評價. 中國循證醫學雜志, 2019, 19(10): 1217-1225.
33. 周紅娟, 喻瀾, 尤春景. 無癥狀性下肢靜脈血栓形成臨床報道1例. 中華物理醫學與康復雜志, 2013, 35(1): 78.

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