Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism: Pooled Analysis of Coagulation Biomarkers From Stars E-3 and Stars J-V.

Abstract

AbstractAbstract 2260 Introduction:Edoxaban is an oral, once-daily, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. Two randomized, double-blind, double-dummy, phase III studies (STARS E-3 and STARS J-V) have been conducted to evaluate the efficacy and safety of edoxaban compared to enoxaparin for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) or total hip arthroplasty (THA). The objective of this pooled analysis was to investigate the effects of edoxaban on key coagulation biomarkers. Methods:Patients (N=1,326) undergoing TKA or THA in Japan and Taiwan were randomized to receive oral edoxaban 30 mg once daily (qd) or subcutaneous enoxaparin 2,000 IU twice daily (bid; equivalent to 20 mg bid) for 11–14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery, which is the standard of care in Japan. Blood samples were collected for coagulation biomarker measurements pre-operation, post-operation (pre-treatment, Day 0), Day 7 (prior to administration of the next dose) and completion day (Day 11–14). The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). The principal safety outcome was the incidence of major and clinically relevant non-major (CRNM) bleeding. Pharmacodynamic endpoints included key coagulation biomarkers such as D-dimer, prothrombin fragment F1+2 (F1+2) and soluble fibrin monomer complex (SFMC). Results:A total of 1,307 patients received at least 1 dose of edoxaban or enoxaparin. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 68 years, mean body weight was 58.8 kg and 83% of patients were female. Overall, edoxaban significantly reduced the incidence of the composite of symptomatic and asymptomatic DVT and PE compared with enoxaparin (5.1% vs 10.7%, P<0.001). The incidence of major and CRNM bleeding events was 4.6% vs 3.7% in the edoxaban and enoxaparin groups, respectively (P=0.427). For both treatment groups, D-dimer and SFMC levels were reduced at Day 7 compared to post-operation/pretreatment levels, then increased slightly by Day 11–14. Levels of F1+2 also decreased by Day 7 in both treatment groups and further decreased by Day 11–14. However, for each coagulation biomarker, levels were significantly lower in the edoxaban group compared to the enoxaparin group at both Day 7 and Day 11–14. (Table, P<0.001). Conclusion:Edoxaban 30 mg qd is superior to enoxaparin 20 mg bid in the prevention of VTE events with significant reduction of D-dimer, F1+2 and SFMC following TKA and THA.Coagulation Biomarkers, all data mean ± SD (median)Pre-operationPost-operation/Pre-treatmentDay 7Day11-14/end of treatmentD-dimer, μg/mLedoxaban0.73 ±0.82 (0.46)9.42±12.56 (5.49)4.43±2.08 (3.99)*5.37±2.52 (4.86)*enoxaparin0.78±0.96 (0.48)10.92±16.22 (5.83)5.53±2.56 (5.08)6.23±3.12 (5.58)F1+2, pMedoxaban273.9±150.6 (243.0)479.7±741.8 (323.0)362.8±164.2 (327.0)*292.1±167.6 (266.5)*enoxaparin277.8±160.9 (242.0)633.2±3234.9 (325.0)463.3±185.6 (422.0)379.6±174.4 (348.5)SFMC, μg/mLedoxaban5.62±17.86 (3.00)32.25±40.47 (13.20)5.71±9.76 (3.30)*6.15±10.73 (4.20)*enoxaparin4.81±8.42 (3.00)34.72±45.62 (12.9)6.82±13.99 (4.10)7.23±11.78 (5.00)*Wilcoxon test: P<0.001 vs enoxaparin; SFMC = soluble fibrin monomer complex Disclosures:Fuji:Daiichi Sankyo: Consultancy; Bayer: Consultancy; Century Medical: Consultancy; Showa Ikakogyo: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Bayer: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Bayer: Consultancy; Toyama Chemical: Consultancy.