Coagulation Biomarkers and Clinical Outcomes in Elderly Patients With Nonvalvular Atrial Fibrillation: ANAFIE Subcohort Study

Yukihiro Koretsune; Takeshi Yamashita; Masaharu Akao; Hirotsugu Atarashi; Takanori Ikeda; Ken Okumura; Wataru Shimizu; Shinya Suzuki; Hiroyuki Tsutsui; Kazunori Toyoda; Atsushi Hirayama; Masahiro Yasaka; Takenori Yamaguchi; Satoshi Teramukai; Tetsuya Kimura; Yoshiyuki Morishima; Atsushi Takita; Hiroshi Inoue

doi:10.1016/j.jacasi.2023.06.004

Coagulation Biomarkers and Clinical Outcomes in Elderly Patients With Nonvalvular Atrial Fibrillation: ANAFIE Subcohort Study

JACC Asia. 2023 Aug 15;3(4):595-607. doi: 10.1016/j.jacasi.2023.06.004. eCollection 2023 Aug.

Authors

Yukihiro Koretsune¹, Takeshi Yamashita², Masaharu Akao³, Hirotsugu Atarashi⁴, Takanori Ikeda⁵, Ken Okumura⁶, Wataru Shimizu², Shinya Suzuki⁷, Hiroyuki Tsutsui⁸, Kazunori Toyoda⁹, Atsushi Hirayama¹⁰, Masahiro Yasaka¹¹, Takenori Yamaguchi⁹, Satoshi Teramukai¹², Tetsuya Kimura¹³, Yoshiyuki Morishima¹³, Atsushi Takita¹⁴, Hiroshi Inoue¹⁵

Affiliations

¹ National Hospital Organization Osaka National Hospital, Osaka, Japan.
² The Cardiovascular Research Institute, Tokyo, Japan.
³ Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
⁴ AOI Hachioji Hospital, Tokyo, Japan.
⁵ Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan.
⁶ Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan.
⁷ Division of Cardiology, Nippon Medical School Department of Medicine, Tokyo, Japan.
⁸ Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
⁹ Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
¹⁰ Osaka Police Hospital, Osaka, Japan.
¹¹ Department of Cerebrovascular Medicine and Neurology, Cerebrovascular Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
¹² Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹³ Primary Medical Science Department, Daiichi Sankyo, Tokyo, Japan.
¹⁴ Data Intelligence Department, Daiichi Sankyo Co, Ltd, Tokyo, Japan.
¹⁵ Saiseikai Toyama Hospital, Toyama, Japan.

Abstract

Background: Little is known about the relationship between coagulation biomarkers and clinical outcomes in patients with atrial fibrillation (AF) treated with anticoagulants, especially direct oral anticoagulants (DOACs) and warfarin.

Objectives: This subcohort study evaluated the association between coagulation biomarkers and clinical outcomes in elderly Japanese patients with nonvalvular AF using the ANAFIE (All Nippon AF In the Elderly) Registry.

Methods: Patients with a definitive diagnosis of nonvalvular AF and aged ≥75 years at enrollment were included. At enrollment, biomarker levels for D-dimer, thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), and soluble fibrin monomer complex (SFMC), along with data on anticoagulant use, were recorded.

Results: Of the 3,194 patients, 95.1% were using oral anticoagulants (OACs) (71.7% DOACs, 23.4% warfarin). D-dimer, TAT, and F1+2 levels, as well as the proportion of patients with a positive SFMC, were lower among those receiving OACs compared with those not receiving OACs. In the DOAC group, higher levels of D-dimer (≥1.0 μg/mL) and TAT (>3 ng/mL) were significantly associated with increased incidences of cardiovascular (CV) events (stroke, myocardial infarction, cardiac intervention, heart failure, and CV death), all-cause death, and CV death. In the warfarin group, higher levels of D-dimer were significantly associated with increased rates of all-cause death, higher levels of TAT with increased major bleeding, and positive SFMC with increased major bleeding and CV events.

Conclusions: Higher levels of coagulation biomarkers were associated with a higher risk of worse clinical outcomes, and the relationships between the coagulation biomarkers and outcomes differed between the DOAC and warfarin groups. (Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation All Nippon AF In Elderly Registry-ANAFIE Registry; UMIN000024006).

Keywords: D-dimer; all-cause death; coagulation biomarker; prothrombin; stroke; systemic embolic events.