Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry

Yuji Mizokami; Takatsugu Yamamoto; Hirotsugu Atarashi; Takeshi Yamashita; Masaharu Akao; Takanori Ikeda; Yukihiro Koretsune; Ken Okumura; Wataru Shimizu; Hiroyuki Tsutsui; Kazunori Toyoda; Atsushi Hirayama; Masahiro Yasaka; Takenori Yamaguchi; Satoshi Teramukai; Tetsuya Kimura; Jumpei Kaburagi; Atsushi Takita; Hiroshi Inoue

doi:10.1371/journal.pone.0240859

Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry

PLoS One. 2020 Nov 5;15(11):e0240859. doi: 10.1371/journal.pone.0240859. eCollection 2020.

Authors

Yuji Mizokami¹, Takatsugu Yamamoto², Hirotsugu Atarashi³, Takeshi Yamashita⁴, Masaharu Akao⁵, Takanori Ikeda⁶, Yukihiro Koretsune⁷, Ken Okumura⁸, Wataru Shimizu⁹, Hiroyuki Tsutsui¹⁰, Kazunori Toyoda¹¹, Atsushi Hirayama¹², Masahiro Yasaka¹³, Takenori Yamaguchi¹¹, Satoshi Teramukai¹⁴, Tetsuya Kimura¹⁵, Jumpei Kaburagi¹⁵, Atsushi Takita¹⁶, Hiroshi Inoue¹⁷

Affiliations

¹ Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
² Department of Medicine, Teikyo University, Itabashi City, Tokyo, Japan.
³ Minami Hachioji Hospital, Hachioji, Tokyo, Japan.
⁴ The Cardiovascular Research Institute, Minato City, Tokyo, Japan.
⁵ National Hospital Organization Kyoto Medical Center, Fushimi Ward, Kyoto, Japan.
⁶ Toho University Omori Medical Center, Ota City, Tokyo, Japan.
⁷ National Hospital Organization Osaka National Hospital, Chuo Ward, Osaka, Japan.
⁸ Saiseikai Kumamoto Hospital, Minami Ward, Kumamoto, Japan.
⁹ Nippon Medical School, Bunkyo City, Tokyo, Japan.
¹⁰ Kyushu University, Higashi Ward, Fukuoka, Japan.
¹¹ National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
¹² Osaka Police Hospital, Tennoji Ward, Osaka, Japan.
¹³ National Hospital Organization Kyushu Medical Center, Chuo Ward, Fukuoka, Japan.
¹⁴ Kyoto Prefectural University of Medicine, Kamigyo Ward, Kyoto, Japan.
¹⁵ Medical Science Department, Daiichi Sankyo Co., Ltd., Chuo City, Tokyo, Japan.
¹⁶ Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan.
¹⁷ Saiseikai Toyama Hospital, Toyama, Toyama, Japan.

Abstract

The real-world status of proton pump inhibitor (PPI) use in patients with atrial fibrillation (AF) receiving antithrombotic treatment is largely unknown. The All Nippon AF In the Elderly (ANAFIE) Registry, a prospective, multicenter, observational study, aimed to determine treatment patterns, risk factors, and outcomes among elderly (aged ≥75 years) Japanese non-valvular AF (NVAF) patients in the real-world clinical setting. The present subanalysis of the ANAFIE Registry determined the PPI prescription status of 32,490 elderly Japanese NVAF patients. Patients were stratified by PPI use (PPI+) or no PPI use (PPI-). Risk scores for stroke (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), anticoagulant use, time in therapeutic range (TTR) for warfarin, and anticoagulant/antiplatelet combination use were evaluated. PPIs were used in 11,981 (36.9%) patients. Compared with the PPI- group, the PPI+ group included a greater proportion of female patients (45.2% vs 41.3%; P <0.0001) and had significantly higher CHADS2, CHA2DS2-VASc, and HAS-BLED scores (P <0.0001 for each) as well as higher prevalences of several comorbidities. In the PPI+ group, 54.6% of patients did not have gastrointestinal (GI) disorders and were likely prescribed a PPI to prevent GI bleeding events. Most of the patients with a GI disorder in the PPI+ group had reflux esophagitis. Compared with patients not receiving anticoagulants, a significantly higher proportion of patients receiving anticoagulants received PPIs. For patients receiving anticoagulants, antiplatelet drugs, and both drugs, rates of PPI use were 34.1%, 44.1%, and 53.5%, respectively (P <0.01). Although the rate of PPI use was the highest for NVAF patients receiving both antiplatelet and anticoagulants, no clear differences were observed in the anticoagulants used. These data suggest that PPIs were actively prescribed in high-risk cases and may have been used to prevent GI bleeding among elderly NVAF patients receiving antithrombotic drugs. Trial registration: UMIN000024006.

Publication types

Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Anticoagulants / administration & dosage
Anticoagulants / adverse effects
Anticoagulants / therapeutic use
Atrial Fibrillation / complications
Atrial Fibrillation / drug therapy*
Cohort Studies
Drug Therapy, Combination
Female
Hemorrhage / epidemiology
Hemorrhage / etiology
Hemorrhage / prevention & control
Humans
Japan / epidemiology
Male
Platelet Aggregation Inhibitors / administration & dosage
Platelet Aggregation Inhibitors / adverse effects
Platelet Aggregation Inhibitors / therapeutic use
Prospective Studies
Proton Pump Inhibitors / administration & dosage
Proton Pump Inhibitors / therapeutic use*
Registries
Risk Factors
Stroke / epidemiology
Stroke / etiology
Stroke / prevention & control

Substances

Anticoagulants
Platelet Aggregation Inhibitors
Proton Pump Inhibitors

Associated data

UMIN-CTR/UMIN000024006

Grants and funding

This study was supported by Daiichi Sankyo Co., Ltd., Tokyo, Japan, in the form of salaries for authors Tetsuya Kimura, Jumpei Kaburagi, and Atsushi Takita. Yuji Mizokami received research funding from Daiichi Sankyo, and remuneration from Daiichi Sankyo. Takatsugu Yamamoto received remuneration from Nippon Boehringer Ingelheim, Bristol-Myers Squibb, Takeda Pharmaceutical, Otsuka Pharmaceutical, and AstraZeneca. Hirotsugu Atarashi received remuneration from Daiichi Sankyo. Takeshi Yamashita 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. Masaharu Akao received research funding from Bayer and Daiichi Sankyo, and remuneration from Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Bayer, and Daiichi Sankyo. Takanori Ikeda received research funding from Daiichi Sankyo and Bayer, and remuneration from Daiichi Sankyo, Bayer, Nippon Boehringer Ingelheim, and Bristol-Myers Squibb. Yukihiro Koretsune received remuneration from Daiichi Sankyo, Bayer, and Nippon Boehringer Ingelheim. Ken Okumura received remuneration from Nippon Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Medtronic. Wataru Shimizu received research funding from Bristol-Myers Squibb, Daiichi Sankyo, and Nippon Boehringer Ingelheim, and patent royalties/licensing fees from Daiichi Sankyo, Pfizer Japan, Bristol-Myers Squibb, Bayer, and Nippon Boehringer Ingelheim. Hiroyuki Tsutsui 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. Kazunori Toyoda received remuneration from Daiichi Sankyo, Bayer, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim. Atsushi Hirayama received research funding from Daiichi Sankyo and Bayer, and remuneration from Bayer, Daiichi Sankyo, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim. Masahiro Yasaka received research funding from Nippon Boehringer Ingelheim, and remuneration from Nippon Boehringer Ingelheim, Daiichi Sankyo, Bayer, Bristol-Myers Squibb, and Pfizer Japan. Takenori Yamaguchi received remuneration from Daiichi Sankyo and Bristol-Myers Squibb. Satoshi Teramukai received research funding from Nippon Boehringer Ingelheim and remuneration from Daiichi Sankyo. Hiroshi Inoue received remuneration from Daiichi Sankyo, Bayer, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.