title: Non-valvular atrial fibrillation patients with low CHADS2 scores benefit from warfarin therapy according to propensity score matching subanalysis using the J-RHYTHM Registry.
abstract: BACKGROUND
  Recently, direct-acting oral anticoagulants (DOACs) have been introduced, with increasing use in patients with non-valvular atrial fibrillation (NVAF). However, warfarin continues to be widely used and the benefits and risks of warfarin in NVAF patients warrant closer inspection.
  
  
  METHODS
  Thromboembolism, major hemorrhage, and total and cardiovascular mortalities were analyzed in 7,406 NVAF patients in the J-RHYTHM Registry from January to July 2009, prior to DOAC introduction. Propensity score matching analysis was performed to reduce the differences in clinical characteristics between non-anticoagulant (n=1002) and warfarin (n=6404) cohorts to reassess warfarin outcomes over 2years.
  
  
  RESULTS
  The incidence of thromboembolism was significantly greater in the non-anticoagulant cohort (3.0%) than in the warfarin cohort (1.5%, P<0.001) with less frequent major hemorrhage in the non-anticoagulant cohort (0.8%) than in the warfarin cohort (2.1%, P=0.009). Using propensity score matching, new subsets (n=896 each) were obtained, with matching of the clinical characteristics between warfarin and non-anticoagulant subsets. The warfarin subset had lower risk factors compared with the total warfarin cohort. The incidence of thromboembolism was higher in the non-anticoagulant subset (2.9%) than in the warfarin subset (0.7%, P<0.001). However, major hemorrhage was not significantly different between the two subsets.
  
  
  CONCLUSIONS
  Although warfarin was associated with a significantly higher incidence of hemorrhage in the unmatched cohorts, propensity score matching revealed that warfarin reduced thromboembolism without a significant increase in hemorrhage in the matched subsets with lower risks. Propensity score matching reduced selection bias and provided rational comparisons although it had indwelling limitations.
authors.affiliation: Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: chishaki@hs.med.kyushu-u.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Chishaki
authors.affiliation: Department of administration, University of Niigata Prefecture, Niigata, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai
authors.affiliation: Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Japan Community Health Care Organization Yufuin Hospital, Oita, Japan.
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Saikawa
authors.affiliation: Second Department of Internal Medicine, Toyama University Hospital, Toyama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Atarashi
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Division of Biostatistics and Clinical Epidemiology, University of Toyama, Toyama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: Department of Cardiology Hokko Memorial Hospital Hokkaido, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Health Administration Center Asahikawa Medical University Hokkaido, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Internal Medicine 1, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.affiliation: Cardiology Department, International Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: International University of Health and Welfare, Mita Hospital, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medicine and Dental Science, Niigata, Japan.
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.affiliation: Graduate School of Health Science, Niigata University School of Medicine, Niigata, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Chinushi
authors.affiliation: Nagoya University, School of Medicine, Aichi, Japan.
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
authors.affiliation: Department of Cardiology, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Watanabe
authors.affiliation: Institute for Clinical Research, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Koretsune
authors.affiliation: Department of Advanced Cardiovascular Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okuyama
authors.affiliation: Faculty of Health Sciences, Yamaguchi Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan; Department of Cardiovascular Medicine, Tottori University Hospital, Tottori, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Igawa
authors.affiliation: Kagawa Prefectural Shirotori Hospital, Kagawa, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Bando
authors.affiliation: Department of Cardiology, Chikamori Hospital, Kochi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fukatani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Atrial fibrillation; Hemorrhage; Propensity score matching; Thromboembolism; Warfarin