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

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).

Informations de copyright

© 2023 The Authors.

Déclaration de conflit d'intérêts

This research was supported by Daiichi Sankyo Co, Ltd. Dr Koretsune has received remuneration from Daiichi Sankyo, Bristol Myers Squibb, and Nippon Boehringer Ingelheim. Dr Yamashita has received research funding from Bristol Myers Squibb, Bayer, and Daiichi Sankyo; manuscript fees from Daiichi Sankyo and Bristol Myers Squibb; and remuneration from Daiichi Sankyo, Bayer, Pfizer Japan, and Bristol Myers Squibb. Dr Akao has received research funding from Bayer and Daiichi Sankyo; and remuneration from Bristol Myers Squibb, Nippon Boehringer Ingelheim, Bayer, and Daiichi Sankyo. Dr Atarashi has received remuneration from Daiichi Sankyo. Dr Ikeda has received research funding from Daiichi Sankyo and Bayer; and remuneration from Daiichi Sankyo, Bayer, and Pfizer Japan. Dr Okumura has received remuneration from Nippon Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Medtronic. Dr Shimizu has received research funding from Bristol Myers Squibb, Daiichi Sankyo, and Nippon Boehringer Ingelheim; and remuneration from Daiichi Sankyo, Pfizer Japan, Bristol Myers Squibb, Bayer, and Nippon Boehringer Ingelheim. Dr Suzuki has received research funding from Mitsubishi-Tanabe and Daiichi Sankyo; and remuneration from Bristol Myers Squibb and Daiichi Sankyo. Dr Tsutsui has received research funding from Daiichi Sankyo and Nippon Boehringer Ingelheim; remuneration from Daiichi Sankyo, Bayer, Nippon Boehringer Ingelheim, and Pfizer Japan; scholarship funding from Daiichi Sankyo; and consultancy fees from Pfizer Japan, Bayer, and Nippon Boehringer Ingelheim. Dr Toyoda has received lecture honoraria from Daiichi-Sankyo, Otsuka, Novartis, Abbott, Bayer, and Bristol Myers Squibb outside the submitted work. Dr Hirayama has participated in a course endowed by Boston Scientific Japan; has received research funding from Daiichi Sankyo and Bayer; and remuneration from Bayer, Daiichi Sankyo, Bristol Myers Squibb, and Nippon Boehringer Ingelheim. Dr Yasaka has received research funding from Nippon Boehringer Ingelheim; and remuneration from Nippon Boehringer Ingelheim, Daiichi Sankyo, Bayer, Bristol Myers Squibb, and Pfizer Japan. Dr Yamaguchi has acted as an Advisory Board member of Daiichi Sanky;o and received remuneration from Daiichi Sankyo and Bristol Myers Squibb. Dr Teramuki has received research funding from Nippon Boehringer Ingelheim; and remuneration from Daiichi Sankyo, Sanofi, Takeda, Chugai Pharmaceutical, Solasia Pharma, Bayer, Sysmex, Nipro, NapaJen Pharma, Gunze, Kaneka, Kringle Pharma, and Atworking. Drs Kimura, Morishima, and Takita are employees of Daiichi Sankyo. Dr Inoue has received remuneration from Daiichi Sankyo, and Bristol Myers Squibb; and consultancy fees from Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.