Abstract

Abstract 3320

Introduction:

Edoxaban is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. The aim of this non-inferiority trial was to determine the efficacy and safety of edoxaban compared with enoxaparin sodium (enoxaparin) after total hip arthroplasty (THA) in Japan.

Methods:

This was a randomized, double-blind, double-dummy, enoxaparin-controlled, multicenter trial. Patients were randomized to oral edoxaban 30 mg once daily (QD) or subcutaneous enoxaparin 2,000 IU, equivalent to 20 mg, twice daily (BID) for 11 to 14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery which is the Japanese standard of care. The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), and pulmonary embolism (PE). The primary safety outcome was the incidence of major and clinically relevant non-major bleeding.

Results:

A total of 610 patients were randomized. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 62.8 years and mean body weight was 57.4 kg (Efficacy analysis set). The primary efficacy outcome occurred in 6 of 255 (2.4%) patients receiving edoxaban and 17 of 248 (6.9%) patients receiving enoxaparin (relative risk reduction=65.7%; absolute risk difference -4.5%, 95% CI, -8.6% to -0.9%; P<0.001 for non-inferiority; P=0.0157 for superiority). The thromboembolic events were all asymptomatic DVT (Table). No symptomatic DVT or PE was observed in both treatment groups. The incidence of major and clinically relevant non-major bleeding events was 2.6% (8/303) vs 3.7% (11/301) in the edoxaban and enoxaparin groups, respectively (P=0.475). Major bleeding occurred in 0.7% of the edoxaban group and 2.0% of the enoxaparin group. The rates of elevated serum aminotransferase levels of more than 3 times the upper limit of normal was 2.6% with edoxaban versus 10% with enoxaparin.

Conclusions:

The STARS J-V trial demonstrated that oral edoxaban 30 mg QD has efficacy superior to enoxaparin 2,000 IU BID in the prevention of thromboembolic events following THA and is associated with a similar incidence of major and clinically relevant non-major bleeding events.

 Edoxaban 30 mg QD(N=255) Enoxaparin 2,000 IU BID(N=248) 
Any VTE, N (%)95% CI 6 (2.4%)1.1 – 5.0 17 (6.9%)4.3 – 10.7 
P-value  P<0.001, ††P=0.0157 
Asymptomatic Proximal DVT, N (%)95% Cl 1 (0.4%)0.1 – 2.2 2 (0.8%)0.2 – 2.9 
Asymptomatic Distal DVT, N (%)95% Cl 6 (2.4%)1.1 – 5.0 16 (6.5%)4.0 – 10.2 
Symptomatic DVT, N (%)95% Cl 0 (0.0%)0 – 1.5 0 (0.0%)0 – 1.5 
 Edoxaban 30 mg QD(N=255) Enoxaparin 2,000 IU BID(N=248) 
Any VTE, N (%)95% CI 6 (2.4%)1.1 – 5.0 17 (6.9%)4.3 – 10.7 
P-value  P<0.001, ††P=0.0157 
Asymptomatic Proximal DVT, N (%)95% Cl 1 (0.4%)0.1 – 2.2 2 (0.8%)0.2 – 2.9 
Asymptomatic Distal DVT, N (%)95% Cl 6 (2.4%)1.1 – 5.0 16 (6.5%)4.0 – 10.2 
Symptomatic DVT, N (%)95% Cl 0 (0.0%)0 – 1.5 0 (0.0%)0 – 1.5 

Non-inferiority: FM-test (Significant level : One-sided P<0.025)

††

Superiority: FM-test (Significant level : Two-sided P<0.05)

Disclosures:

Fuji:Astellas: Consultancy; Showa Ikakogyo: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Astellas: Consultancy; GlaxoSmithkline: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Toyama Chemical: Consultancy. Koretsune:Daiichi Sankyo: Consultancy, National Lead Investigator. Yamashita:Daiichi Sankyo: Consultancy, National Lead Investigator; Otsuka Pharmaceutical: Paid instructor; Sanofi-aventis: Paid instructor; Teijin Pharma: Paid instructor. Nakamura:Daiichi Sankyo: Consultancy; GlaxoSmithkline: Consultancy; Astellas: Consultancy.

Author notes

*

Asterisk with author names denotes non-ASH members.