Edoxaban versus enoxaparin for the prevention of venous thromboembolism after total knee or hip arthroplasty: pooled analysis of coagulation biomarkers and primary efficacy and safety endpoints from two phase 3 trials

Yohko Kawai; Takeshi Fuji; Satoru Fujita; Tetsuya Kimura; Kei Ibusuki; Kenji Abe; Shintaro Tachibana

doi:10.1186/s12959-016-0121-1

Edoxaban versus enoxaparin for the prevention of venous thromboembolism after total knee or hip arthroplasty: pooled analysis of coagulation biomarkers and primary efficacy and safety endpoints from two phase 3 trials

Thromb J. 2016 Dec 1:14:48. doi: 10.1186/s12959-016-0121-1. eCollection 2016.

Authors

Yohko Kawai¹, Takeshi Fuji², Satoru Fujita³, Tetsuya Kimura⁴, Kei Ibusuki⁴, Kenji Abe⁵, Shintaro Tachibana⁶

Affiliations

¹ International University of Health and Welfare, 8-10-16 Akasaka, Minato-ku, Tokyo 107-0052 Japan.
² Department of Orthopaedic Surgery, Japan Community Healthcare Organization Osaka Hospital, 4-2-78, Fukushima, Fukushima-ku, Osaka 553-0003 Japan.
³ Department of Orthopaedic Surgery, Takarazuka Daiichi Hospital, 19-5 Kogetsu-cho, Takarazuka, 665-0832 Japan.
⁴ Daiichi Sankyo Co., Ltd, 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo 103-8426 Japan.
⁵ Clinical Data & Biostatistics Department, Daiichi Sankyo Co. Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710 Japan.
⁶ Department of Orthopaedic Surgery, Mishuku Hospital, 5-33-12 Shimomeguro, Meguro-ku, Tokyo 153-0051 Japan.

Abstract

Background: 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).

Methods: In 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.

Results: A 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).

Conclusions: Edoxaban 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 registration: Clintrials.gov NCT01181102 and NCT01181167. Both registered 8/12/2010.

Keywords: Biomarker; DOAC; Total hip arthroplasty; Total knee arthroplasty; VTE prophylaxis.

Associated data

ClinicalTrials.gov/NCT01181102
ClinicalTrials.gov/NCT01181167