Characteristics and clinical outcomes of Japanese patients with venous thromboembolism receiving under-dose rivaroxaban: subanalysis of J’xactly

Abstract

Objective

Rivaroxaban is commonly prescribed to prevent venous thromboembolism (VTE). Although lower than standard dosages (under-dosing) may be administered in the real-world setting, data on subsequent clinical outcomes in Japanese patients are lacking.

Methods

The prospective, multicenter, observational J’xactly study enrolled patients with acute symptomatic/asymptomatic deep vein thromboses (DVT), pulmonary embolism (PE), or both, who were prescribed rivaroxaban. This subanalysis investigated patient characteristics and outcomes associated with rivaroxaban under-dosing.

Results

Among 1016 evaluable patients, 667 (65.6%) received an initial standard dosage of rivaroxaban (30 mg/day) and 349 (34.4%) received an initial under-dosage (20 mg/day, n = 22; 15 mg/day, n = 282; and 10 mg/day, n = 45). Those receiving an under-dose had significantly lower body weight and slower pulse rate compared with the standard-dose group regardless of DVT or PE status. Under-dosing was common for distal DVTs, but less frequent for massive/submassive PEs. There were no differences between under-dose and standard-dose groups in the incidences of recurring symptomatic VTEs (DVT: 1.77% vs. 3.35% per patient-year, p = .138; PE: 0.84% vs. 2.84% per patient-year, p = .208) or major bleeding (DVT: 3.55% vs. 3.41% per patient-year, p = .960; PE: not observed vs. 2.83% per patient-year, p = .132).

Conclusions

In the real-world setting, rivaroxaban under-dosing for patients with VTE occurred in those with lower body weight, slower pulse rate, distal DVT, or non-massive PEs. There were no statistically significant differences in the clinical outcomes for patients received under-dose of rivaroxaban at the discretion of the physicians in the clinical practice compared with those received standard dose of rivaroxaban.

Keywords:

• Direct-acting oral anticoagulants
• off-label dosage
• rivaroxaban
• venous thromboembolism
• under-dose

Transparency

Declaration of funding

This study was financially supported by Bayer Yakuhin, Ltd.

Declaration of financial/other relationships

D.F. has no relationships relevant to the contents of this paper to disclose. Y.O. has received lecture fees, research funding, scholarship funds, and donations from Bayer Yakuhin, Ltd.; lecture fees, scholarship funds, and donations from Daiichi-Sankyo Co., Ltd.; research funding from Bristol-Myers Squibb; scholarship funds and donations from Johnson & Johnson; and is associated with endowed departments sponsored by Boston Scientific Japan, Abbott Medical Japan, Medtronic Japan Co., Ltd., Nihon Kohden Co., Nihon Medi-Physics Co., Ltd., and Japan Lifeline Co., Ltd. I.F. has received lecture fees from Bayer Yakuhin, Ltd., Daiichi-Sankyo Co., Ltd., and Pfizer Japan Inc. M.N. has no relationships relevant to the contents of this paper to disclose. N.Y. has received lecture fees from Bayer Yakuhin, Ltd., Pfizer Japan Inc., and Daiichi-Sankyo Co., Ltd. M.T. has no relationships relevant to the contents of this paper to disclose. H.M. has no relationships relevant to the contents of this paper to disclose. Ta.Y. has received lecture fees, manuscript fees, and research funding from Daiichi-Sankyo Co., Ltd., Bristol-Myers Squibb, and Bayer Yakuhin, Ltd., and lecture fees from Ono Pharmaceutical Co., Ltd., Toa Eiyo, Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. T.I. has received lecture fees from Bayer Yakuhin, Ltd., Bristol-Myers Squibb, and Nippon Boehringer Ingelheim Co., Ltd., and research funding from Daiichi-Sankyo Co., Ltd. M.M. has received lecture fees from Bayer Yakuhin, Ltd. Ts.Y. has no relationships relevant to the contents of this paper to disclose. A.H. has received lecture fees from Toa Eiyo, Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Amgen Astellas BioPharma, and AstraZeneca Plc.; lecture fees, scholarship funds, and donations from Bayer Yakuhin, Ltd., Sanofi S.A., Astellas Pharma Inc., Bristol-Myers Squibb, and Daiichi-Sankyo Co., Ltd; scholarship funds, donations, and is associated with endowed departments sponsored by Boston Scientific Japan and Otsuka Pharmaceutical Co., Ltd.; scholarship funds and donations from Takeda Pharmaceutical Co., Ltd., and Nihon Medi-Physics Co., Ltd.; and is associated with endowed departments sponsored by Fukuda Denshi Co., Ltd, Abbott Medical Japan Co., Ltd., Japan Lifeline Co., Ltd., and Medtronic Japan Co., Ltd. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Drs. Fukamachi, Okumura, and Hirayama contributed to the conception and design, data acquisition, and data analysis and interpretation. All authors contributed to drafting of the article. They also revised the manuscript critically for important intellectual content and approved the final version of the manuscript for publication.

Acknowledgements

The authors wish to thank the centers that participated in this study and all of the patients who provided their consent to participate. We thank Serina Nakamoto and other members of Mebix for their assistance in the management of data collection, storage, and analysis. We also thank Masahiro Takita of Mebix for encouragement and assistance with the reporting of our findings, and Clare Lee, PhD, of Edanz Pharma, for assistance with English editing of the manuscript.

Data availability statement

The deidentified participant data will not be shared.