Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants

Matsuoka, Yuki; Sakamoto, Daisuke; Sunaga, Akihiro; Okada, Katsuki; Nakatani, Daisaku; Kitamura, Tetsuhisa; Kanda, Takashi; Minamiguchi, Hitoshi; Watanabe, Ryuta; Nagashima, Kouichi; Higuchi, Yoshiharu; Okumura, Yasuo; Sotomi, Yohei; Sakata, Yasushi

doi:https://doi.org/10.1016/j.ijcard.2025.133942

Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants

Matsuoka, Yuki; Sakamoto, Daisuke; Sunaga, Akihiro et al.

International Journal of Cardiology, 2025, 443, 133942

Number of Access:67（2025-12-11 21:28 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103289

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Title	Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants
Creator	CreatorName Matsuoka, Yuki
	CreatorName Sakamoto, Daisuke
	NRID 1000010812258 1000010812258 ORCID 0000-0003-2590-6696 0000-0003-2590-6696 researchmap permalink 10812258 10812258 Scopus Author ID 56647970400 56647970400 CreatorName Sunaga, Akihiro
	NRID 1000020776489 1000020776489 ORCID 0000-0002-1725-781X 0000-0002-1725-781X researchmap permalink katsuki_okada katsuki_okada Scopus Author ID 13613369100 13613369100 CreatorName Okada, Katsuki
	NRID 1000060444535 1000060444535 ORCID 0000-0002-1534-2033 0000-0002-1534-2033 researchmap permalink dsyma dsyma Scopus Author ID 6603545219 6603545219 CreatorName Nakatani, Daisaku
	NRID 1000030639810 1000030639810 ORCID 0000-0003-0107-0580 0000-0003-0107-0580 researchmap permalink Kitamura_T Kitamura_T Scopus Author ID 22234282700 22234282700 CreatorName Kitamura, Tetsuhisa
	CreatorName Kanda, Takashi
	NRID 1000090648495 1000090648495 CreatorName Minamiguchi, Hitoshi
	NRID 1000070899129 1000070899129 CreatorName Watanabe, Ryuta
	CreatorName Nagashima, Kouichi
	CreatorName Higuchi, Yoshiharu
	NRID 1000020624159 1000020624159 CreatorName Okumura, Yasuo
	NRID 1000090885253 1000090885253 ORCID 0000-0002-7564-2978 0000-0002-7564-2978 researchmap permalink sotomiyohei sotomiyohei Scopus Author ID 57115149800 57115149800 CreatorName Sotomi, Yohei
	NRID 1000000397671 1000000397671 ORCID 0000-0002-5618-4721 0000-0002-5618-4721 researchmap permalink C4589 C4589 Scopus Author ID 35395964700 35395964700 CreatorName Sakata, Yasushi
Subject	Anticoagulation
	Atrial fibrillation
	Bleeding risk
	Direct oral anticoagulants
	Ischemic events
	Renal function
Description	Matsuoka Y., Sakamoto D., Sunaga A., et al. Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants. International Journal of Cardiology 443, 133942 (2026); https://doi.org/10.1016/j.ijcard.2025.133942.
Abstract	Background: Renal function influences the pharmacokinetics of oral anticoagulants in atrial fibrillation (AF), potentially affecting both efficacy and bleeding risk. However, its differential impact across specific agents remains unclear. In this study, we aimed to evaluate the association between renal function and ischemic and bleeding risks in patients with AF, with analyses stratified by anticoagulant type. Methods: We analyzed 7239 patients with non-valvular AF from the DIRECT-Extend registry, a pooled dataset of three large-scale registries. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault formula and categorized into ≥50, 30 to <50, and 15 to <30 mL/min. The primary ischemic endpoint was stroke or systemic embolism, and the primary bleeding endpoint was major bleeding. Cox proportional hazard models and restricted cubic spline analyses assessed associations between CrCl and outcomes, with subgroup analyses by anticoagulant type. Results: Lower CrCl was associated with older age, female sex, and greater comorbidity burden. Impaired renal function was significantly associated with higher ischemic and bleeding risks. Spline analysis demonstrated a continuous increase in both risks with declining CrCl, with a nonlinear relationship for bleeding. Subgroup analyses revealed significant associations between reduced CrCl and ischemic risk in patients on dabigatran, rivaroxaban, edoxaban, and warfarin. Increased bleeding risk was evident for edoxaban and warfarin at lower CrCl levels. No significant association was observed between CrCl and either endpoint in patients receiving apixaban. Conclusion: In this large real-world cohort, declining renal function was associated with increased ischemic and bleeding risks, highlighting the importance of renal function–based risk assessment in the management of anticoagulation therapy.
Publisher	Elsevier Ireland Ltd
Source Title	International Journal of Cardiology
Volume (Issue)	443
Page	133942
Date of Issued	2025-09-30
Language	English
Handle URL	https://hdl.handle.net/11094/103289
PISSN	01675273
eISSN	18741754
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.ijcard.2025.133942
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	International Journal of Cardiology. 2025, 443, p. 133942
DC.title	Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants
DC.creator	Matsuoka, Yuki
	Sakamoto, Daisuke
	Sunaga, Akihiro
	Okada, Katsuki
	Nakatani, Daisaku
	Kitamura, Tetsuhisa
	Kanda, Takashi
	Minamiguchi, Hitoshi
	Watanabe, Ryuta
	Nagashima, Kouichi
	Higuchi, Yoshiharu
	Okumura, Yasuo
	Sotomi, Yohei
	Sakata, Yasushi
DC.publisher	Elsevier Ireland Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-09-30
DC.identifier	https://doi.org/10.1016/j.ijcard.2025.133942
DC.subject	Anticoagulation
	Atrial fibrillation
	Bleeding risk
	Direct oral anticoagulants
	Ischemic events
	Renal function
DC.description	Matsuoka Y., Sakamoto D., Sunaga A., et al. Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants. International Journal of Cardiology 443, 133942 (2026); https://doi.org/10.1016/j.ijcard.2025.133942.
DCTERMS.abstract	Background: Renal function influences the pharmacokinetics of oral anticoagulants in atrial fibrillation (AF), potentially affecting both efficacy and bleeding risk. However, its differential impact across specific agents remains unclear. In this study, we aimed to evaluate the association between renal function and ischemic and bleeding risks in patients with AF, with analyses stratified by anticoagulant type. Methods: We analyzed 7239 patients with non-valvular AF from the DIRECT-Extend registry, a pooled dataset of three large-scale registries. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault formula and categorized into ≥50, 30 to <50, and 15 to <30 mL/min. The primary ischemic endpoint was stroke or systemic embolism, and the primary bleeding endpoint was major bleeding. Cox proportional hazard models and restricted cubic spline analyses assessed associations between CrCl and outcomes, with subgroup analyses by anticoagulant type. Results: Lower CrCl was associated with older age, female sex, and greater comorbidity burden. Impaired renal function was significantly associated with higher ischemic and bleeding risks. Spline analysis demonstrated a continuous increase in both risks with declining CrCl, with a nonlinear relationship for bleeding. Subgroup analyses revealed significant associations between reduced CrCl and ischemic risk in patients on dabigatran, rivaroxaban, edoxaban, and warfarin. Increased bleeding risk was evident for edoxaban and warfarin at lower CrCl levels. No significant association was observed between CrCl and either endpoint in patients receiving apixaban. Conclusion: In this large real-world cohort, declining renal function was associated with increased ischemic and bleeding risks, highlighting the importance of renal function–based risk assessment in the management of anticoagulation therapy.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103289
citation_title	Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants
citation_author	Matsuoka, Yuki
	Sakamoto, Daisuke
	Sunaga, Akihiro
	Okada, Katsuki
	Nakatani, Daisaku
	Kitamura, Tetsuhisa
	Kanda, Takashi
	Minamiguchi, Hitoshi
	Watanabe, Ryuta
	Nagashima, Kouichi
	Higuchi, Yoshiharu
	Okumura, Yasuo
	Sotomi, Yohei
	Sakata, Yasushi
citation_publisher	Elsevier Ireland Ltd
citation_language	English
citation_date	2025-09-30
citation_journal_title	International Journal of Cardiology
citation_volume	443
citation_firstpage	133942
citation_doi	https://doi.org/10.1016/j.ijcard.2025.133942
citation_public_url	https://hdl.handle.net/11094/103289

Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants

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