Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism: Pooled Analysis of Venous Thromboembolism and Bleeding From STARS E-3 and STARS J-V

Edoxaban is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. Two randomized, double-blind, double-dummy, phase 3 studies (STARS E-3 and STARS J-V) have been conducted to evaluate the efficacy and safety of edoxaban compared with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee (TKA) or hip arthroplasty (THA). The objective of this pooled analysis was to investigate the effects of edoxaban on VTE and bleeding in key subgroups.

Patients (N=1326) undergoing TKA or THA in Japan and Taiwan were randomized to receive oral edoxaban 30 mg once daily (qd) or subcutaneous enoxaparin 2000 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. 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 nonmajor (CRNM) bleeding.

A total of 1307 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 and mean body weight was 58.8 kg. Over 70% of patients received physiotherapy (intermittent pneumatic compression, elastic stocking). 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). Subgroup analysis showed that edoxaban numerically reduced the incidence of the composite efficacy endpoint regardless of age or body weight. The effect was statistically significant in patients <75 years of age and in those <70 kg. Edoxaban was also significantly more effective than enoxaparin in the presence or absence of concomitant physiotherapy. The incidence of major and CRNM bleeding events was 4.6% vs 3.7% in the edoxaban and enoxaparin groups, respectively (P=0.427). Subgroup analysis of major and CRNM bleeding indicated no significant difference between edoxaban and enoxaparin in any of the patient subgroups evaluated, based on age, weight, or creatinine clearance.

Edoxaban 30 mg qd is superior to enoxaparin 20 mg bid in the prevention of VTE events following TKA and THA without a statistically significant increase in bleeding in important patient subgroups likely to receive this treatment.

Fuji:Daiichi Sankyo: Consultancy; Astellas: Consultancy; Showa Ikakogyo: Consultancy; Bayer: Consultancy. Fujita:Astellas: Consultancy; GlaxoSmithKline: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Toyama Chemical: Consultancy; Bayer: Consultancy.