Abstract
BackgroundThe objective of this analysis was to assess the effects of edoxaban compared with enoxaparin on key coagulation biomarkers and present pooled primary efficacy and safety results from phase 3 STARS E-3 and STARS J-V trials for prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) or total hip arthroplasty (THA).MethodsIn the randomized, double-blind, double-dummy, multicenter, STARS E-3 and STARS J-V trials, patients received edoxaban 30 mg or enoxaparin 2000 IU (20 mg) twice daily for 11 to 14 days. The studies were conducted in Japan and Taiwan; enoxaparin dosing was based on Japanese label recommendations. The primary efficacy endpoint was incidence of VTE; the safety endpoint was major or clinically relevant nonmajor (CRNM) bleeding. Blood samples were taken at presurgical evaluation, pretreatment (postsurgery), predose on day 7, predose on completion of treatment, and at a follow-up examination 25 to 35 days after the last dose of study drug for D-dimer, prothrombin fragment 1 + 2 (F1+2), and soluble fibrin monomer complex (SFMC) measurement.ResultsA total of 716 patients enrolled in STARS E-3 and 610 patients enrolled in STARS J-V; 1326 patients overall. This analysis included 657 patients who received edoxaban 30 mg QD and 650 patients who received enoxaparin 20 mg BID. Incidence of VTE was 5.1 and 10.7% for edoxaban and enoxaparin, respectively (P <0.001). Incidence of combined major and CRNM bleeding was 4.6 and 3.7% for edoxaban and enoxaparin, respectively (P = 0.427). On day 7, mean D-dimer (4.4 vs 5.5 μg/mL), F1+2 (363 vs 463 pmol/L), and SFMC (5.7 vs 6.8 μg/mL) were lower in edoxaban-treated patients relative to enoxaparin-treated patients, respectively (P <0.0001 for all). At end of treatment, mean D-dimer (5.4 vs 6.2 μg/mL), F1+2 (292 vs 380 pmol/L), and SFMC (6.2 vs 7.2 μg/mL) were lower in edoxaban-treated patients relative to enoxaparin-treated patients (P <0.0001 for all).ConclusionsEdoxaban was superior to enoxaparin in prevention of VTE following TKA and THA, with comparable rates of bleeding events. Relative to enoxaparin, edoxaban significantly reduced D-dimer, F1+2, and SFMC.Trial registrationClintrials.gov NCT01181102 and NCT01181167. Both registered 8/12/2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s12959-016-0121-1) contains supplementary material, which is available to authorized users.
Highlights
The objective of this analysis was to assess the effects of edoxaban compared with enoxaparin on key coagulation biomarkers and present pooled primary efficacy and safety results from phase 3 STARS E-3 and STARS J-V trials for prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) or total hip arthroplasty (THA)
In Japan, edoxaban [3], a direct oral anticoagulant (DOAC) selective inhibitor of activated factor Xa (FXa), and enoxaparin [4], an injectable low-molecular-weight heparin (LMWH), are both indicated for prophylaxis of deep vein thrombosis (DVT) following TKA, THA, or hip fracture surgery
The approval of edoxaban for the primary prevention of VTE after lower limb orthopedic surgery was based on evidence collected during three phase 3 studies evaluating the safety and efficacy of edoxaban compared with enoxaparin for prevention of VTE in Japanese or Taiwanese patients following TKA [5], THA [6], and hip fracture surgery [7]
Summary
The objective of this analysis was to assess the effects of edoxaban compared with enoxaparin on key coagulation biomarkers and present pooled primary efficacy and safety results from phase 3 STARS E-3 and STARS J-V trials for prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) or total hip arthroplasty (THA). The approval of edoxaban for the primary prevention of VTE after lower limb orthopedic surgery was based on evidence collected during three phase 3 studies evaluating the safety and efficacy of edoxaban compared with enoxaparin for prevention of VTE in Japanese or Taiwanese patients following TKA [5], THA [6], and hip fracture surgery [7]. Assessment of coagulation biomarkers can provide information on the effect of anticoagulants in relation to dose and clinical response
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