A non-interventional comparison of rivaroxaban with standard of care for thromboprophylaxis after major orthopaedic surgery in 17,701 patients with propensity score adjustment

 

 Buy Article Permissions and Reprints

Summary

Rivaroxaban demonstrated superior efficacy and a similar safety profile to enoxaparin for the prevention of venous thromboembolism in the phase III RECORD programme in patients undergoing elective hip or knee replacement surgery. The XAMOS study investigated adverse events, including bleeding and thromboembolic events, in patients receiving rivaroxaban for thromboprophylaxis in routine clinical practice. XAMOS was a non-interventional, open-label cohort study in patients undergoing major orthopaedic surgery of the hip or knee (predominantly elective arthroplasty), in which rivaroxaban was compared with other pharmacological thromboprophylaxis. All adverse events were documented, including symptomatic thromboembolic and bleeding events. Crude and adjusted incidences based on propensity score subclasses were calculated and compared between the rivaroxaban and standard-of-care groups. A total of 17,701 patients were enrolled from 252 centres in 37 countries. Crude incidences of symptomatic thromboembolic events three months after surgery in the safety population were 0.89% in the rivaroxaban group (n=8,778) and 1.35% in the standard-of-care group (n=8,635; odds ratio [OR] 0.65; 95% confidence interval [CI] 0.49–0.87), and 0.91% and 1.31% (weighted) in the propensity score-adjusted analysis (OR 0.69; 95% CI 0.56–0.85), respectively. Treatment-emergent major bleeding events (as defined in the RECORD studies) occurred in 0.40% and 0.34% of patients in the rivaroxaban and standard-of-care groups in the safety population (OR 1.19; 95% CI 0.73–1.95), and in 0.44% versus 0.33% (weighted) in the propensity score-adjusted analysis (OR 1.35; 95% CI 0.94–1.93), respectively. This study in unselected patients confirmed the favourable benefit–risk profile of rivaroxaban seen in the RECORD programme.

• References

• 1 Warwick D, Friedman RJ, Agnelli G. et al. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br 2007; 89: 799-807.
  CrossrefPubMedGoogle Scholar
• 2 Eriksson BI, Borris LC, Friedman RJ. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-2775.
  CrossrefPubMedGoogle Scholar
• 3 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.
  CrossrefPubMedGoogle Scholar
• 4 Lassen MR, Ageno W, Borris LC. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-2786.
  CrossrefPubMedGoogle Scholar
• 5 Turpie AGG, Lassen MR, Davidson BL. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673-1680.
  CrossrefPubMedGoogle Scholar
• 6 Rubin DB. The design versus the analysis of observational studies for causal effects: parallels with the design of randomized trials. Stat Med 2007; 26: 20-36.
  CrossrefPubMedGoogle Scholar
• 7 Turpie AGG, Lassen MR, Eriksson BI. et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost 2011; 105: 444-453.
  Article in Thieme ConnectPubMedGoogle Scholar
• 8 European Medicines Agency. Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/05/WC500127902.pdf . Accessed October 25, 2013.
  PubMedGoogle Scholar
• 9 Turpie AGG, Schmidt AC, Kreutz R. et al. Rationale and design of XAMOS: noninterventional study of rivaroxaban for prophylaxis of venous thromboem-bolism after major hip and knee surgery. Vasc Health Risk Manag 2012; 8: 363-370.
  PubMedGoogle Scholar
• 10 Holland PW. Statistics and causal inference. J Am Statistical Assoc 1986; 81: 945-960.
  CrossrefPubMedGoogle Scholar
• 11 Rubin DB. Estimating causal effects of treatments in randomized and nonran-domized studies. J Educ Psychol 1974; 66: 668-701.
  CrossrefPubMedGoogle Scholar
• 12 Rubin DB. Bayesian inference for causal effects: The role of randomization. Annals of Statistics 1978; 6: 34-58.
  CrossrefPubMedGoogle Scholar
• 13 Schulman S, Angeras U, Bergqvist D. et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8: 202-204.
  CrossrefPubMedGoogle Scholar
• 14 Weber JCP. Epidemiology of adverse reactions to nonsteroidal antiinflamma-tory drugs. In: Advances in Inflammatory Research. Raven Press 1984: 1-7.
  PubMedGoogle Scholar
• 15 Turpie AGG, Kreutz R, Llau J. et al. Management consensus guidance for the use of rivaroxaban - an oral, direct Factor Xa inhibitor. Thromb Haemost 2012; 108: 876-886.
  Article in Thieme ConnectPubMedGoogle Scholar

• Supplementary Material