Yukiko Matsumura-Nakano1, Satoshi Shizuta1, Akihiro Komasa1, Takeshi Morimoto2, Hisaki Masuda3, Hiroki Shiomi1, Koji Goto4, Kentaro Nakai5, Hisashi Ogawa6, Atsushi Kobori7, Yutaka Kono8, Kazuaki Kaitani9, Satoru Suwa10, Takeshi Aoyama11, Mamoru Takahashi12, Yasuhiro Sasaki, Yuko Onishi13, Toshiaki Mano14, Mitsuo Matsuda15, Makoto Motooka16, Hirofumi Tomita17, Moriaki Inoko18, Takatoshi Wakeyama19, Nobuhisa Hagiwara20, Kengo Tanabe21, Masaharu Akao6, Katsumi Miyauchi22, Junji Yajima23, Keiichi Hanaoka24, Yoshihiro Morino25, Kenji Ando3, Yutaka Furukawa7, Yoshihisa Nakagawa26, Koichi Nakao27, Ken Kozuma28, Kazushige Kadota29, Kazuo Kimura30, Kazuya Kawai31, Takafumi Ueno32, Ken Okumura, Takeshi Kimura1. 1. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (Y.M.-N., S.S., A.K., H.S., T.K.). 2. Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan (T.M.). 3. Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan (H.M., K.A.). 4. Department of Cardiology, Saitama Medical University International Medical Center, Japan (K.G.). 5. Department of Cardiovascular Medicine, Uji Tokushukai Medical Center, Japan (K.N.). 6. Department of Cardiology, National Hospital Organization Kyoto Medical Center, Japan (H.O., M.A.). 7. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Japan (A.K., Y.F.). 8. Kono Clinic, Kyoto, Japan (Y.K.). 9. Department of Cardiovascular Medicine, Japanese Red Cross Otsu Hospital, Japan (K.K.). 10. Department of Cardiology, Juntendo University Shizuoka Hospital, Izunokuni, Japan (S.S.). 11. Division of Cardiology, Shimada Municipal Hospital, Japan (T.A.). 12. Department of Cardiology, Shimabara Hospital, Kyoto, Japan (M.T.). 13. Department of Cardiology, Hiratsuka Kyosai Hospital, Japan (Y.O.). 14. Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan (T.M.). 15. Division of Cardiology, Kishiwada City Hospital, Japan (M.M.). 16. Division of Cardiology, Shizuoka General Hospital, Japan (M.M.). 17. Department of Cardiology, Hirosaki University Graduate School of Medicine, Japan (H.T.). 18. Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan (M.I.). 19. Division of Cardiology, Tokuyama Central Hospital, Shunan, Japan (T.W.). 20. Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Japan (N.H.). 21. Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan (K.T.). 22. Department of Cardiovascular Medicine, Juntendo University Hospital, Tokyo, Japan (K.M.). 23. Department of Cardiovascular Medicine, The Cardiovascular Institute, Tokyo, Japan (J.Y.). 24. Hanaoka Seishu Memorial Cardiovascular Clinic, Sapporo, Japan (K.H.). 25. Department of Cardiology, Iwate Medical University, Morioka, Japan (Y.M.). 26. Department of Cardiology, Tenri Hospital, Japan (Y.N.). 27. Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Japan (K.N.). 28. Department of Cardiology, Teikyo University Hospital, Tokyo, Japan (K.K.). 29. Department of Cardiology, Kurashiki Central Hospital, Japan (K.K.). 30. Division of Cardiology, Yokohama City University Medical Center, Japan (K.K.). 31. Department of Cardiovascular Medicine, Chikamori Hospital, Kochi, Japan (K.K.). 32. Division of Cardiovascular Medicine, Kurume University Hospital, Japan (T.U.).
Abstract
BACKGROUND: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting. METHODS: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months. RESULTS:Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively. CONCLUSIONS: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.
RCT Entities:
BACKGROUND: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting. METHODS: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months. RESULTS: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively. CONCLUSIONS: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.
Authors: Davide Capodanno; Deepak L Bhatt; John W Eikelboom; Keith A A Fox; Tobias Geisler; C Michael Gibson; Jose Ramon Gonzalez-Juanatey; Stefan James; Renato D Lopes; Roxana Mehran; Gilles Montalescot; Manesh Patel; P Gabriel Steg; Robert F Storey; Pascal Vranckx; Jeffrey I Weitz; Robert Welsh; Uwe Zeymer; Dominick J Angiolillo Journal: Nat Rev Cardiol Date: 2020-01-17 Impact factor: 32.419
Authors: Samer Al Said; Samer Alabed; Klaus Kaier; Audrey R Tan; Christoph Bode; Joerg J Meerpohl; Daniel Duerschmied Journal: Cochrane Database Syst Rev Date: 2019-12-19