Z Orthop Unfall 2024; 162(04): 368-381
DOI: 10.1055/a-1994-7500
Original Article

Efficacy and Safety of Rivaroxaban and Enoxaparin for Thromboprophylaxis Among Total Hip Arthroplasty Patients: A Systematic Review and Meta-Analysis

Wirksamkeit und Sicherheit von Rivaroxaban und Enoxaparin zur Thromboseprophylaxe bei Patienten mit Hüfttotalendoprothesen: Eine systematische Überprüfung und Meta-Analyse
Chong Wang
1   Orthopaedics, Lishui Central Hospital, Zheijiang, China
,
Shuhua Lan
1   Orthopaedics, Lishui Central Hospital, Zheijiang, China
,
Panpan Xie
1   Orthopaedics, Lishui Central Hospital, Zheijiang, China
,
Ruifeng Yang
1   Orthopaedics, Lishui Central Hospital, Zheijiang, China
› Author Affiliations

Abstract

Background Venous thromboembolism (VTE) is one of the major and potentially life-threatening complications following major orthopedic surgeries. Research evidence comparing the effectiveness of rivaroxaban and enoxaparin for thromboprophylaxis specific to total hip arthroplasty (THA) has been limited. Hence, this review was done to compare the efficacy and safety of rivaroxaban against enoxaparin for thromboprophylaxis after THA.

Materials and Methods We conducted a search in databases including Medline, EMBASE, ScienceDirect, Google Scholar, and Cochrane Library from inception until May 2021. Randomized controlled trials directly comparing the effectiveness of rivaroxaban and enoxaparin for thromboprophylaxis among patients undergoing THA were eligible for inclusion. Outcome parameters assessed were efficacy in terms of total VTE and all-cause mortality, major VTE, deep vein thrombosis, symptomatic VTE, and safety in terms of major bleeding events, clinically relevant nonmajor bleeding events, minor bleeding events, total bleeding events, drug-related adverse events, and wound infection. We performed a meta-analysis with a random effects model and reported a pooled risk ratio (RR) with a 95% confidence interval (CI).

Results Eleven studies, including 9057 participants, were analyzed. Amongst efficacy outcomes, VTE and all-cause mortality pooled an RR of 0.58 (95% CI: 0.34–0.99), major VTE pooled an RR of 0.37 (95% CI: 0.15–0.90), deep vein thrombosis pooled an RR of 0.57 (95% CI: 0.32–1.02), and symptomatic VTE pooled an RR of 0.51 (95% CI: 0.30–0.87). Amongst safety outcomes, major bleeding events pooled an RR of 1.18 (95% CI: 0.77–1.80), total bleeding events pooled an RR of 1.12 (95% CI: 0.93–1.34), drug-related adverse event pooled an RR of 0.99 (95% CI: 0.87–1.12), and wound infection pooled an RR of 1.11 (95% CI: 0.58–2.14).

Conclusion Rivaroxaban is a more efficacious drug in terms of VTE and all-cause mortality compared to enoxaparin following THA, and rivaroxaban was non-inferior in terms of safety profiles such as wound infection, bleeding, and drug-related adverse events.

Zusammenfassung

Hintergrund Venöse Thromboembolien (VTE) sind eine der wichtigsten und potenziell lebensbedrohlichen Komplikationen nach größeren orthopädischen Eingriffen. Die Forschungsergebnisse zum Vergleich der Wirksamkeit von Rivaroxaban und Enoxaparin für die Thromboseprophylaxe bei Hüftgelenkersatzoperationen (HTEP) waren bisher begrenzt. Daher wurde diese Übersichtsarbeit durchgeführt, um die Wirksamkeit und Sicherheit von Rivaroxaban und Enoxaparin bei der Thromboseprophylaxe nach HTEP zu vergleichen.

Materialien und Methoden Wir führten eine Suche in den Datenbanken Medline, EMBASE, ScienceDirect, Google Scholar und Cochrane Library von Anfang an bis Mai 2021 durch. Eingeschlossen wurden randomisierte kontrollierte Studien, die die Wirksamkeit von Rivaroxaban und Enoxaparin zur Thromboseprophylaxe bei Patienten, die sich einer HTEP unterziehen, direkt vergleichen. Als Ergebnisparameter wurden die Wirksamkeit in Bezug auf VTE-Gesamt- und Gesamtmortalität, schwere VTE, tiefe Venenthrombose, symptomatische VTE sowie die Sicherheit in Bezug auf schwere Blutungsereignisse, klinisch relevante nicht-schwere Blutungsereignisse, leichte Blutungsereignisse, Gesamtblutungsereignisse, arzneimittelbedingte unerwünschte Ereignisse und Wundinfektionen untersucht. Wir haben eine Meta-Analyse mit einem Modell mit zufälligen Effekten durchgeführt und ein gepooltes Risikoverhältnis (RR) mit einem 95%-Konfidenzintervall (KI) angegeben.

Ergebnisse Es wurden 11 Studien mit 9.057 Teilnehmern ausgewertet. Bei den Wirksamkeitsnachweisen ergab sich für VTE und Gesamtmortalität ein gepooltes RR von 0,58 (95%-KI: 0,34–0,99), für schwere VTE ein gepooltes RR von 0,37 (95%-KI: 0,15–0,90), für TVT ein gepooltes RR von 0,57 (95%-KI: 0,32–1,02) und für symptomatische VTE ein gepooltes RR von 0,51 (95%-KI: 0,30–0,87). Bei den Sicherheitsergebnissen hatten schwere Blutungen ein gepooltes RR von 1,18 (95%-KI: 0,77–1,80), Gesamtblutungen ein gepooltes RR von 1,12 (95%-KI: 0,93–1,34), arzneimittelbedingte unerwünschte Ereignisse ein gepooltes RR von 0,99 (95%-KI: 0,87–1,12) und Wundinfektionen ein gepooltes RR von 1,11 (95%-KI: 0,58–2,14).

Schlussfolgerung: Rivaroxaban ist ein wirksameres Medikament in Bezug auf VTE und Gesamtmortalität im Vergleich zu Enoxaparin nach HTEP, und beide waren in Bezug auf Sicherheitsprofile wie Wundinfektion, Blutung und arzneimittelbedingte unerwünschte Ereignisse nicht unterlegen.

Supplementary Material



Publication History

Received: 13 September 2022

Accepted after revision: 06 December 2022

Article published online:
30 January 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Santana DC, Emara AK, Orr MN. et al. An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020. Medicina 2020; 56: 416 DOI: 10.3390/medicina56090416. (PMID: 32824931)
  • 2 Friedman RJ. Extended thromboprophylaxis after hip or knee replacement. Orthopedics 2003; 26: s225-s230 DOI: 10.3928/0147-7447-20030202-05. (PMID: 12597230)
  • 3 Geerts WH, Heit JA, Clagett GP. et al. Prevention of venous thromboembolism. Chest 2001; 119: 132S-175S DOI: 10.1378/chest.119.1_suppl.132s. (PMID: 11157647)
  • 4 Flevas DA, Megaloikonomos PD, Dimopoulos L. et al. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev 2018; 3: 136-148 DOI: 10.1302/2058-5241.3.170018. (PMID: 29780621)
  • 5 Ansell J, Hirsh J, Poller L. et al. The pharmacology and management of the vitamin K antagonists. In: 7th ACCP Conf Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 204S-233S
  • 6 Davies LM, Richardson GA, Cohen AT. Economic evaluation of enoxaparin as postdischarge prophylaxis for deep vein thrombosis (DVT) in elective hip surgery. Value Health 2000; 3: 397-406 DOI: 10.1046/j.1524-4733.2000.36005.x. (PMID: 16464199)
  • 7 Dahl OE, Pleil AM. Investment in prolonged thromboprophylaxis with dalteparin improves clinical outcomes after hip replacement. J Thromb Haemost 2003; 1: 896-906 DOI: 10.1046/j.1538-7836.2003.00236.x. (PMID: 12871354)
  • 8 Friedman RJ, Gallus AS, Cushner FD. et al. Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty. Curr Med Res Opin 2008; 24: 87-97
  • 9 Ufer M. Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost 2010; 103: 572-585 DOI: 10.1160/TH09-09-0659. (PMID: 20135071)
  • 10 Hull RD, Yusen RD, Bergqvist D. Assessing the safety profiles of new anticoagulants for major orthopaedic surgery thromboprophylaxis. Clin Appl Thromb Hemost 2009; 15: 377-388 DOI: 10.1177/1076029609338712. (PMID: 19608549)
  • 11 Perzborn E, Strassburger J, Wilmen A. et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59–7939—an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005; 3: 514-521 DOI: 10.1111/j.1538-7836.2005.01166.x. (PMID: 15748242)
  • 12 Bagherifard A, Gharanizadeh K, Salehpour M. et al. Comparing Prophylactic Effect of Rivaroxaban and Enoxaparin on Thromboembolism After Total Hip or Knee Arthroplasty. J Res Orthop Sci 2020; 7: 13-22
  • 13 Eriksson BI, Borris LC, Dahl OE. et al. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59–7939), for thromboprophylaxis after total hip replacement. Circulation 2006; 114: 2374-2381 DOI: 10.1161/CIRCULATIONAHA.106.642074. (PMID: 17116766)
  • 14 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: 121-128
  • 15 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: 1660-1665 DOI: 10.1111/j.1538-7836.2007.02644.x. (PMID: 17663737)
  • 16 Eriksson BI, Borris LC, Friedman RJ. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. New Engl J Med 2008; 358: 2765-2775 DOI: 10.1056/NEJMoa0800374. (PMID: 18579811)
  • 17 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: 31-39 DOI: 10.1016/S0140-6736(08)60880-6. (PMID: 18582928)
  • 18 Nieto JA, Espada NG, Merino RG. et al. Dabigatran, rivaroxaban and apixaban versus enoxaparin for thomboprophylaxis after total knee or hip arthroplasty: pool-analysis of phase III randomized clinical trials. Thromb Res 2012; 130: 183-191 DOI: 10.1016/j.thromres.2012.02.011. (PMID: 22425218)
  • 19 Cao YB, Zhang JD, Shen H. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol 2010; 66: 1099-1108 DOI: 10.1007/s00228-010-0889-z. (PMID: 20812009)
  • 20 Huang HF, Li SS, Yang XT. et al. Rivaroxaban versus enoxaparin for the prevention of venous thromboembolism after total knee arthroplasty: a meta-analysis. Medicine (Baltimore) 2018; 97: e13465 DOI: 10.1097/MD.0000000000013465. (PMID: 30508972)
  • 21 Sterne JA, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898 DOI: 10.1136/bmj.l4898. (PMID: 31462531)
  • 22 Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, UK: John Wiley & Sons, Ltd; 2008
  • 23 Chai W. Effectiveness of rivaroxaban in preventing venous thromboembolism after total hip replacement in adults. Beijing: Chinese People’s Liberation Army Academy of Continuing Medical Sciences, Chinese People’s Liberation Army General Hospital, PLA General Hospital of Surgery (Orthopedics); 2008
  • 24 Kanan PS, Schwartsmann CR, Boschin LC. et al. Comparative study between rivaroxaban and enoxaparin in deep venous thromboembolism prophylaxis in patients submitted to total hip arthroplasty. Rev Bras Ortop 2008; 43: 319-328
  • 25 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: 600-607 DOI: 10.1160/TH15-07-0527. (PMID: 26790579)
  • 26 Ligu L, Jini M. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. Int J Orthop Sci 2020; 6: 90-95
  • 27 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 2020; 28: 2309499020938865 DOI: 10.1177/2309499020938865. (PMID: 32700655)
  • 28 Wei ZH, Zhang MH, Zhao B. et al. Different doses of rivaroxaban versus enoxaparin for prevention of venous thromboembolism after total hip arthroplasty: a meta-analysis of safety and efficacy. Chin J Tissue Eng Res 2016; 20: 8022
  • 29 Feng W, Wu K, Liu Z. et al. Oral direct factor Xa inhibitor versus enoxaparin for thromboprophylaxis after hip or knee arthroplasty: Systemic review, traditional meta-analysis, dose–response meta-analysis and network meta-analysis. Thromb Res 2015; 136: 1133-1144 DOI: 10.1016/j.thromres.2015.10.009. (PMID: 26498222)
  • 30 Kaul S, Diamond GA. Does rivaroxaban provide a clinically relevant favorable benefit-risk profile compared with enoxaparin after hip or knee arthroplasty?. J Am Coll Cardiol 2010; 5: A172-E1616
  • 31 National Clinical Guideline Centre – Acute and Chronic Conditions (UK). Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital. London: Royal College of Physicians (UK); 2010