Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation Patients With High Bleeding Risks: ANAFIE Registry

Ken Okumura; Takeshi Yamashita; Masaharu Akao; Hirotsugu Atarashi; Takanori Ikeda; Yukihiro Koretsune; 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.2022.07.008

Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation Patients With High Bleeding Risks: ANAFIE Registry

JACC Asia. 2022 Nov 15;2(6):720-733. doi: 10.1016/j.jacasi.2022.07.008. eCollection 2022 Nov.

Authors

Ken Okumura¹, Takeshi Yamashita², Masaharu Akao³, Hirotsugu Atarashi⁴, Takanori Ikeda⁵, Yukihiro Koretsune⁶, Wataru Shimizu⁷, Shinya Suzuki², Hiroyuki Tsutsui⁸, Kazunori Toyoda⁹, Atsushi Hirayama¹⁰, Masahiro Yasaka¹¹, Takenori Yamaguchi⁹, Satoshi Teramukai¹², Tetsuya Kimura¹³, Yoshiyuki Morishima¹³, Atsushi Takita¹⁴, Hiroshi Inoue¹⁵

Affiliations

¹ Division of Cardiology, Saiseikai Kumamoto Hospital, Kumamoto, Japan.
² The Cardiovascular 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 National Hospital Organization Osaka National Hospital, Osaka, Japan.
⁷ Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
⁸ Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁹ Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, 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 Co, Ltd, Tokyo, Japan.
¹⁴ Data Intelligence Department, Daiichi Sankyo Co, Ltd, Tokyo, Japan.
¹⁵ Saiseikai Toyama Hospital, Toyama, Japan.

Abstract

Background: Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking.

Objectives: This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N = 32,275) data.

Methods: Patients were classified into high-risk (age: ≥80 years; CHADS₂ score: ≥2; and presence of ≥1 bleeding risk factor: creatinine clearance of 15-30 mL/minute, prior bleeding at critical sites, body weight of ≤45 kg, or continuous antiplatelet use) and reference groups.

Results: In the high-risk (n = 7,104) and reference (n = 25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95% CI: 0.36-0.79) and all-cause death (HR: 0.65; 95% CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95% CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding.

Conclusions: High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006).

Keywords: AF, atrial fibrillation; CrCl, creatinine clearance; DOAC, direct-acting oral anticoagulant; NVAF, nonvalvular atrial fibrillation; OAC, oral anticoagulant; SE, systemic embolism; TTR, time in the therapeutic range; anticoagulants; atrial fibrillation; high risk; outcomes; very elderly.