Shortened length of hospital stay with rivaroxaban in patients with symptomatic venous thromboembolism in Japan: the J-EINSTEIN pulmonary embolism and deep vein thrombosis program

Abstract

Background:

In Japan, the standard of care for the treatment of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) consists of intravenous unfractionated heparin (UFH) followed by warfarin, which was recently compared with rivaroxaban, an oral factor Xa inhibitor, in randomized trials.

Aim:

To examine the length of hospital stay in patients with PE and/or DVT receiving rivaroxaban compared to Japanese standard therapy in the Japanese (J)-EINSTEIN PE and DVT program.

Methods:

Open-label, randomized clinical trials that compared 3, 6, or 12 months of rivaroxaban with UFH and warfarin in patients with acute, confirmed symptomatic proximal PE and/or DVT. Decisions regarding hospital admission and/or discharge were left to the clinical judgment of attending physicians. Analyses were conducted in the intention-to-treat (ITT) population.

Results:

In the ITT population (N = 97), overall patient characteristics were similar in both treatment arms. The median length of stay in rivaroxaban patients was 10.0 days (interquartile range [IQR] 6.0 to 15.0 days) while it was 15.0 days (IQR 9.0 to 22.0) for patients on standard therapy (p = 0.016). All of the four DVT patients who were not hospitalized for the index event were in the rivaroxaban arm.

Conclusions:

Our results suggest that treatment with rivaroxaban may significantly reduce the length of hospital stay in patients hospitalized for PE and/or DVT compared with the current standard of care in Japan, thereby reducing the burden on patients and the healthcare system. The limitations of our study include small sample size and the generalizability of the findings to the real-world setting. Further research is warranted to identify PE and/or DVT patients in Japanese clinical practice who may potentially be managed as outpatients.

Trial registration:

Clinicaltrials.gov: NCT01516814 and NCT01516840.

Keywords: :

• Deep vein thrombosis
• Japan
• Length of stay
• Pulmonary embolism
• Randomized trial
• Rivaroxaban
• Unfractionated heparin
• Venous thromboembolism
• Warfarin

Transparency

Declaration of funding

The program was funded by Bayer Yakuhin Ltd, Japan.

Declaration of financial/other relationships

H.M. has disclosed that he was a paid consultant of Bayer Yakuhin Ltd, Japan in the current analysis, and a member of the J-EINSTEIN data monitoring committee. M.P. has disclosed that he is a consultant advisor for Bayer HealthCare Pharmaceuticals AG. A.W.A.L. has disclosed that he is an employee of Bayer HealthCare Pharmaceuticals AG. E.W.F., Y.M. and M.K. have disclosed that they are employees of Bayer Yakuhin Ltd, Japan.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Members of the J-EINSTEIN study group and affiliations are as follows. Coordinate investigator: Norikazu Yamada, Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Mie, Japan. Central independent adjudication committee (CIAC): Martin H. Prins, Maastricht University Medical Center, Maastricht, The Netherlands. Data monitoring committee (DMC): Shotai Kobayashi, Shimane University Faculty of Medicine, Matsue, Japan; Hiroshi Matsuo, Matsuo Vascular Ultrasound Laboratory, Matsuo Clinic, Suita, Osaka, Japan; Hideki Origasa, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan. We thank Adelphi Values LLC for performing statistical analyses in the current study.