Clinical Review

Decision Making in Venous Thromboembolism

Journal of Clinical Outcomes Management. 2015 May;22(5)

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Rivaroxaban, a TSOAC that targets factor Xa, has also shown efficacy in preventing VTE after knee or hip surgery. The RE-CORD 1-4 studies all focused on the use of rivaroxaban in comparison to enoxaparin and found that rivaroxaban 10 mg once daily was superior to enoxaparin 40 mg once daily in prevention of VTE in total knee and total hip arthroplasty [136–138].Meta-analysis of multiple rivaroxaban VTE prophylaxis trials also demonstrated that rivaroxaban significantly lowered the risk of VTE in these surgical patients in comparison to the use of enoxaparin [139].Prophylactic use of rivaroxaban was also studied in acutely ill hospitalized patients in the MAGELLAN trial. Rivaroxaban 10 mg daily for 35 days was compared to enoxaparin 40 mg daily for 10 days followed by placebo and was found to be noninferior to enoxaparin in reduction of VTE risk at day 10 and superior to placebo at day 35 [140].However, the rate of bleeding, although low in both arms, was higher in the rivaroxaban arm.

Rivaroxaban has been studied in randomized clinical trials for acute treatment of DVT and PE and for extended prophylaxis for recurrent VTE (EINSTEIN-DVT, EINSTEIN-PE and EINSTEIN-Extension, respectively). The treatment strategy for use of rivaroxaban differed from that of dabigatran (in the RE-COVER trial), as rivaroxaban was used upfront as initial anticoagulation rather than after an initial period of parenteral therapy with LMWH or UFH. In both the DVT and PE trials, rivaroxaban was noninferior to standard treatment with enoxaparin followed by warfarin therapy, with no significant difference in major bleeding at 6 months of treatment [141,142].The extension trial also demonstrated that use of rivaroxaban in comparison to placebo for an additional 6 or 12 months after standard therapy was associated with significantly fewer recurrent VTE [141]. These studies led to FDA approval for rivaroxaban for primary prevention of VTE in patients undergoing elective total hip or knee repair surgery, for treatment of acute DVT or PE, and for extended prophylaxis in patients following initial treatment.

The anti-factor Xa TSOAC apixaban has been studied in similar fashion as rivaroxaban. In the AMPLIFY study, apixaban was given at a dose of 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months (as monotherapy, without initial parenteral agent) and compared to enoxaparin followed by warfarin for treatment of acute VTE. Apixaban was as effective as warfarin in terms of recurrent symptomatic VTE or VTE-related death, and was associated with significantly fewer bleeding events [143].Extended-duration apixaban given at treatment dose (5 mg twice daily) or at prophylactic dose (2.5 mg twice daily) for 12 months after completion of treatment-dose apixaban for VTE demonstrated superiority to placebo for extended prophylaxis in AMPLIFY-EXT, and there was no increase in major bleeding compared to placebo [144].Apixaban was recently approved by the FDA for both treatment and secondary prophylaxis of VTE.

More recently, a third anti-factor Xa TSOAC edoxaban demonstrated noninferiority to warfarin in prevention of recurrent symptomatic VTE when administered to patients with DVT or PE at 60 mg once daily for 3 to 12 months [145].Edoxaban also led to significantly less bleeding than warfarin. Edoxaban was recently approved by the FDA for treatment of VTE.