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. 2021 Sep;36(9):1410-1420.
doi: 10.1007/s00380-021-01810-5. Epub 2021 Mar 16.

Ischemic stroke, hemorrhage, and mortality in patients with non-valvular atrial fibrillation and renal dysfunction treated with rivaroxaban: sub-analysis of the EXPAND study

Hirotsugu Atarashi  1 , Shinichiro Uchiyama  2 , Hiroshi Inoue  3 , Takanari Kitazono  4 , Takeshi Yamashita  5 , Wataru Shimizu  6 , Takanori Ikeda  7 , Masahiro Kamouchi  8 , Koichi Kaikita  9 , Koji Fukuda  10 , Hideki Origasa  11 , Hiroaki Shimokawa  12   13
Affiliations

Ischemic stroke, hemorrhage, and mortality in patients with non-valvular atrial fibrillation and renal dysfunction treated with rivaroxaban: sub-analysis of the EXPAND study

Hirotsugu Atarashi et al. Heart Vessels. 2021 Sep.

Abstract

The EXPAND Study demonstrated the effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in routine clinical practice in Japan. This sub-analysis was conducted to reveal the effectiveness and safety of rivaroxaban in Japanese NVAF patients according to baseline creatinine clearance (CrCl) levels and rivaroxaban doses in the EXPAND Study. We examined 6806 patients whose baseline CrCl data were available and classified them into 2 groups: normal renal function group with CrCl ≥ 50 mL/min (n = 5326, 78%) and renal dysfunction group with CrCl < 50 mL/min (n = 1480, 22%). In the normal renal function group, 1609 (30%) received 10 mg/day (under-dose), while in the renal dysfunction group, 108 (7%) received 15 mg/day (over-dose). In the normal renal function group, under-dose of rivaroxaban was associated with higher all-cause mortality, while in the renal dysfunction group, over-dose was associated with higher incidence of major bleeding. In contrast, the incidence of stroke or systemic embolism was not different between the 2 groups regardless of the dose of rivaroxaban. In the propensity score matched analysis to adjust the difference in characteristics according to doses of rivaroxaban, the incidences of clinical outcomes were comparable between the 2 dose groups in both renal function groups. These results indicate that the dose of rivaroxaban should be reduced depending on the renal function, considering the balance between risks of bleeding and ischemia.

Keywords: Creatinine clearance; Non-valvular atrial fibrillation; Renal dysfunction; Rivaroxaban.

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Conflict of interest statement

H.A. has received personal fee from Daiichi Sankyo, outside the submitted work. S.U. has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Sanofi, Dainippon Sumitomo, Otsuka, Takeda, Astellas, AstraZeneka, Sanwa Kagaku, Shionogi, Mitsubishi Tanabe, and Pfizer, outside the submitted work. H.I. has received personal fees from Bayer Healthcare, Boehringer Ingelheim, Daiichi-Sankyo, and Bristol-Myers Squibb, outside the submitted work. T.K. has received grants and personal fees from Daiichi Sankyo, Bayer Yakuhin, Pfizer, Chugai, Boehringer Ingelheim, Mitsubishi Tanabe, Shionogi, Astellas, and MSD; personal fees from Bristol-Myers Squibb, Sanofi, and AstraZeneca; and grants from Takeda, Kissei, Kyowa Hakko Kirin, EA Pharma, Asahi Kasei Medical, Otsuka, Torii, Eisai, Ono, Zeria, and Dainippon Sumitomo, outside the submitted work. T.Y. has received grants and personal fees from Bayer, Daiichi Sankyo, Bristol-Myers Squibb, and Mitsubishi Tanabe; and personal fees from Pfizer, Eisai, Ono Pharmaceutical, Toa Eiyo, and Nippon Boehringer, outside the submitted work. W.S. has received grants and personal fees from Bayer, Daiichi Sankyo, Nippon Boehringer, Bristol-Myers Squibb, Pfizer, Eisai, Ono Pharmaceutical, and Mitsubishi Tanabe, outside the submitted work. T.I reports grants and personal fees from Daiichi-Sankyo, personal fees from Bayer, grants and personal fees from Bristol-Myers Squibb, personal fees from Pfizer, grants from Boehringer Ingelheim, outside the submitted work. M.K. has received personal fees from Tohoku University, during the conduct of the study; and personal fees from Bayer, outside the submitted work. K.K. has received grants from Bayer Yakuhin, Ltd., Daiichi-Sankyo Co., Ltd.; and honoraria from Bayer Yakuhin, Ltd, and Daiichi-Sankyo Co., Ltd., outside the submitted work. K.F. has received personal fees from Bayer, outside the submitted work. H.O. has received personal fees from Daiichi-Sankyo and Bayer, outside the submitted work. H.S. has received personal fees from Bayer, and Daiichi Sankyo, outside the submitted work.

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates for the primary effectiveness endpoints (a) and safety endpoints (b) by creatinine clearance and rivaroxaban doses in the unmatched cohort. CrCl; creatinine clearance
Fig. 2
Fig. 2
Kaplan–Meier estimates for the primary effectiveness endpoints (a) and safety endpoints (b) by creatinine clearance and rivaroxaban doses in the propensity score matched cohort. CrCl; creatinine clearance
See this image and copyright information in PMC

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