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Effect of rivaroxaban on urinary albumin excretion in patients with atrial fibrillation and chronic kidney disease: a randomized trial (X-NOAC)

Hypertension Research volume 43, pages 571–574 (2020)Cite this article

Atrial fibrillation (AF) and chronic kidney disease (CKD) share common risk factors and associations with other conditions, such as metabolic syndrome and cardiovascular diseases [1]. In the general Japanese population, the odds ratio of the presence of AF in subjects with a reduced estimated glomerular filtration rate (eGFR: ≤59 mL/min/1.73 m2) is 2.10 (95% confidence interval 1.21–3.86) compared with those with an eGFR ≥ 90 mL/min/1.73 m2 [2]. Previous studies have demonstrated that the presence of CKD was associated with a greater increase in the risk of stroke and thromboembolic events in patients with AF [3, 4].

In patients with AF and mild to moderate CKD, direct oral anticoagulant (DOAC) therapy showed noninferiority and even mild superiority to warfarin therapy for reducing the risk of stroke and thromboembolic and bleeding events [1, 5, 6]. A retrospective cohort study suggested that DOAC therapy was associated with a delayed decline in renal function [7]. Rivaroxaban is a selective inhibitor of factor Xa that catalyzes thrombin formation in the coagulation cascade. Thrombin has established nonhematologic functions beyond blood coagulation that include endothelial cell senescence and inflammatory responses [8, 9]. Ichikawa et al. [10] recently reported that rivaroxaban attenuated angiotensin II-induced renal injuries partly via inhibition of the protease-activated receptor-2-mediated inflammatory pathway, suggesting that rivaroxaban has the potential to exert renoprotective effects. However, the clinical effects of rivaroxaban on renal function in patients with AF and CKD remain uncertain. Therefore, we investigated the effects of rivaroxaban, compared with those of warfarin, on urinary albumin excretion (UAE) in those patients.

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Acknowledgements

The authors would like to thank the patients and investigators for their participation in the study and Ms. Hiroko Takagi (Saga University, Saga, Japan) for her excellent support as a study secretariat. We also thank Mr. Hirokazu Yamada and Mr. Yasushi Kanamori (Soiken Holdings Inc., Osaka, Japan) for their statistical support.

Funding

The study was funded by Bayer Yakuhin, Ltd.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Saga University, Saga, Japan

    Atsushi Tanaka, Atsuko Chihara, Jun-ichi Oyama & Koichi Node

  2. Department of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama, Japan

    Makoto Suzuki

  3. Department of Internal Medicine, Imari-Arita Kyoritsu Hospital, Matsuura, Japan

    Kazuo Matsunaga

  4. Department of Cardiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan

    Isao Taguchi & Shiro Nakahara

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  1. Atsushi Tanaka
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Contributions

All authors were X-NOAC Study Investigators and contributed to the planning and conduction of the study and data acquisition. KN was a principal investigator in the study. AT analyzed and interpreted the data, prepared the figures and tables, and wrote the paper. All authors critically reviewed the paper and approved the final version of the paper.

Corresponding authors

Correspondence to Atsushi Tanaka or Koichi Node.

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Conflict of interest

MS received remuneration for lecture from Otsuka, Bayer, Daiichi Sankyo, Biotronik, Medtronic, and Fukuda Denshi. JO belonged to the endowed department of Fukuda Denshi. KN received honoraria from Eli Lilly, Astellas, Ono, Takeda, Daiichi Sankyo, Boehringer Ingelheim, MSD, Mitsubishi Tanabe, AstraZeneca; research grants from Amgen, Teijin, Terumo, Mitsubishi Tanabe, Asahi Kasei, Astellas, Boehringer Ingelheim, and Bayer and scholarships from Bayer, Daiichi Sankyo, Teijin, Astellas, Takeda, and Bristol-Myers Squibb. The other authors declare that they have no conflict of interest.

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Tanaka, A., Suzuki, M., Matsunaga, K. et al. Effect of rivaroxaban on urinary albumin excretion in patients with atrial fibrillation and chronic kidney disease: a randomized trial (X-NOAC). Hypertens Res 43, 571–574 (2020). https://doi.org/10.1038/s41440-019-0384-6

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