Akiko Chishaki1, Naoko Kumagai2, Naohiko Takahashi3, Tetsunori Saikawa4, Hiroshi Inoue5, Ken Okumura6, Hirotsugu Atarashi7, Takeshi Yamashita8, Hideki Origasa9, Masayuki Sakurai10, Yuichiro Kawamura11, Isao Kubota12, Kazuo Matsumoto13, Yoshiaki Kaneko14, Satoshi Ogawa15, Yoshifusa Aizawa16, Masaomi Chinushi17, Itsuo Kodama18, Eiichi Watanabe19, Yukihiro Koretsune20, Yuji Okuyama21, Akihiko Shimizu22, Osamu Igawa23, Shigenobu Bando24, Masahiko Fukatani25. 1. Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: chishaki@hs.med.kyushu-u.ac.jp. 2. Department of administration, University of Niigata Prefecture, Niigata, Japan. 3. Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University, Oita, Japan. 4. Japan Community Health Care Organization Yufuin Hospital, Oita, Japan. 5. Second Department of Internal Medicine, Toyama University Hospital, Toyama, Japan. 6. Department of Cardiology, Hirosaki University Graduate School of Medicine, Aomori, Japan. 7. Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan. 8. The Cardiovascular Institute, Tokyo, Japan. 9. Division of Biostatistics and Clinical Epidemiology, University of Toyama, Toyama, Japan. 10. Department of Cardiology Hokko Memorial Hospital Hokkaido, Japan. 11. Health Administration Center Asahikawa Medical University Hokkaido, Japan. 12. Internal Medicine 1, Yamagata University School of Medicine, Yamagata, Japan. 13. Cardiology Department, International Medical Center, Saitama Medical University, Saitama, Japan. 14. Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan. 15. International University of Health and Welfare, Mita Hospital, Tokyo, Japan. 16. Division of Cardiology, Niigata University Graduate School of Medicine and Dental Science, Niigata, Japan. 17. Graduate School of Health Science, Niigata University School of Medicine, Niigata, Japan. 18. Nagoya University, School of Medicine, Aichi, Japan. 19. Department of Cardiology, Fujita Health University School of Medicine, Aichi, Japan. 20. Institute for Clinical Research, National Hospital Organization, Osaka National Hospital, Osaka, Japan. 21. Department of Advanced Cardiovascular Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan. 22. Faculty of Health Sciences, Yamaguchi Graduate School of Medicine, Yamaguchi, Japan. 23. Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan; Department of Cardiovascular Medicine, Tottori University Hospital, Tottori, Japan. 24. Kagawa Prefectural Shirotori Hospital, Kagawa, Japan. 25. Department of Cardiology, Chikamori Hospital, Kochi, Japan.
Abstract
INTRODUCTION: 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. MATERIALS AND 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.
INTRODUCTION: 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. MATERIALS AND 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.