Rivaroxaban versus enoxaparin after total knee arthroplasty

Abstract

The RECORD4 study (May 16, p 1673)1Turpie A Lassen MR Davidson BL et al.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial.Lancet. 2009; 373: 1673-1680Summary Full Text Full Text PDF PubMed Scopus (871) Google Scholar showed that the new oral selective factor Xa inhibitor, rivaroxaban, given at a dose of 10 mg once daily is superior to enoxaparin given at the North-American-approved dose of 30 mg twice daily for the prevention of venous thromboembolism (VTE) after total knee arthroplasty. An earlier trial, the RECORD3 study,2Lassen MR Ageno W Borris LC et al.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty.N Engl J Med. 2008; 358: 2776-2786Crossref PubMed Scopus (1194) Google Scholar showed that rivaroxaban 10 mg once daily was also superior to enoxaparin given at the European-approved dose of 40 mg once daily for prevention of VTE after total knee arthroplasty.2Lassen MR Ageno W Borris LC et al.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty.N Engl J Med. 2008; 358: 2776-2786Crossref PubMed Scopus (1194) Google Scholar To our knowledge, no randomised trials have directly compared the North American and European enoxaparin dosing regimens in patients undergoing knee arthroplasty. Yet, indirect comparisons between the results of the RECORD4 and RECORD3 trials, and between the results of the REMOBILIZE trial3Ginsberg JS Davidson BL Comp PC et al.The oral thrombin inhibitor dabigatran etexilate vs the North America enoxaparin regimen for the prevention of venous thromboembolism after knee arthroplasty surgery.J Arthroplasty. 2009; 24: 1-9Summary Full Text PDF PubMed Google Scholar (which compared the new oral selective factor IIa inhibitor, dabigatran, with enoxaparin 30 mg twice daily) and the REMODEL trial4Eriksson BI Dahl OE Rosencher N et al.Oral dabigatran etexilate vs subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial.J Thromb Hemost. 2007; 5: 2178-2185Crossref PubMed Scopus (923) Google Scholar (dabigatran vs enoxaparin 40 mg once daily) indicate a more modest treatment effect of the new oral drug when compared against the North American enoxaparin dosing regimen than when compared against the European regimen (p≤0·10 for heterogeneity). These results suggest that enoxaparin 30 mg twice daily is substantially more effective than enoxaparin 40 mg once daily for the prevention of VTE in patients undergoing knee arthroplasty (table).TablePrimary outcome (any deep-vein thrombosis, pulmonary embolism, or death) of phase 3 randomised controlled trials comparing enoxaparin 40 mg once daily or 30 mg twice daily with rivaroxaban or dabigatran for the prevention of VTE in patients undergoing knee arthroplastyNorth American regimen (enoxaparin 30 mg twice daily)European regimen (enoxaparin 40 mg once daily)p for heterogeneity*Breslow-Day test for homogeneity.TrialRECORD4 (n=3148)RECORD3 (n=2531)ComparatorRivaroxaban 10 mg once dailyRivaroxaban 10 mg once dailyRelative risk (95% CI)1·46 (1·08–1·98)1·97 (1·53–2·53)0·09TrialREMOBILIZE (n=2610)REMODEL (n=2076)ComparatorDabigatran 220 mg once dailyDabigatran 220 mg once dailyRelative risk (95% CI)0·81 (0·68–0·97)1·03 (0·88–1·22)0·06ComparatorDabigatran 150 mg once dailyDabigatran 150 mg once dailyRelative risk (95% CI)0·75 (0·63–0·89)0·93 (0·80–1·08)0·10* Breslow-Day test for homogeneity. Open table in a new tab The apparently superior efficacy of the North American enoxaparin dosing regimen over the European one might be related either to differences in the total daily dose of enoxaparin (60 mg vs 40 mg, respectively) or the frequency of enoxaparin administration (twice daily vs once daily) because the drug has a half-life of only 5–7 h. Irrespective of the mechanism, however, these data are consistent with the hypothesis that differences in the efficacy of new oral anticoagulants compared with enoxaparin are primarily determined by a contrast in dose intensity rather than differences between the drugs in their pharmacological target. JWE has received research support and/or honoraria from Bayer, Boehringer-Ingelheim, and Sanofi-Aventis. NCR and SD declare that they have no conflicts of interest. Rivaroxaban versus enoxaparin after total knee arthroplasty – Authors' replyThe RECORD programme compared rivaroxaban 10 mg once daily with either the EU or North American approved regimens of enoxaparin (40 mg once daily or 30 mg twice daily). As Nina Raju and colleagues note, factors such as pharmacological target and differences in dose and frequency, as well as timing of initial postoperative drug administration, can affect the safety or efficacy of anticoagulants. However, RECORD4 and the RECORD programme as a whole were not designed to compare different enoxaparin regimens or to provide indirect comparisons on the efficacy of new anticoagulants. Full-Text PDF