Koichi Kaikita1,2, Satoshi Yasuda3,4, Masaharu Akao5, Junya Ako6, Tetsuya Matoba7, Masato Nakamura8, Katsumi Miyauchi9, Nobuhisa Hagiwara10, Kazuo Kimura11, Atsushi Hirayama12, Kunihiko Matsui13, Hisao Ogawa14. 1. Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Japan (K. Kaikita). 2. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan (K. Kaikita). 3. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.Y.). 4. National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (S.Y.). 5. Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.). 6. Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan (J.A.). 7. Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan (T.M.). 8. Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Meguro-ku, Tokyo, Japan (M.N.). 9. Department of Cardiovascular Medicine, Juntendo Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, Japan (K. Miyauchi). 10. Department of Cardiology, Tokyo Women's Medical University, Shinjuku-ku, Japan (N.H.). 11. Cardiovascular Center, Yokohama City University Medical Center, Kanagawa, Japan (K. Kimura). 12. Department of Cardiology, Osaka Police Hospital, Japan (A.H.). 13. Department of General Medicine and Primary Care, Kumamoto University Hospital, Japan (K. Matsui). 14. Kumamoto University, Japan (H.O.).
Abstract
BACKGROUND: Early bleeding after percutaneous coronary intervention is associated with increased risk of death and myocardial infarction; however, the association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains unclear in patients with atrial fibrillation and stable coronary artery disease. We thus aimed to investigate this association. METHODS: The AFIRE trial (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) was a multicenter, open-label trial conducted in Japan. This post hoc analysis included 2215 patients with atrial fibrillation and stable coronary artery disease treated with rivaroxaban or rivaroxaban plus an antiplatelet agent. MACCE was defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The association of bleeding with subsequent MACCE risk was investigated using time-adjusted Cox multivariate analysis after adjusting for baseline characteristics and time from bleeding. Bleeding events were classified according to the International Society on Thrombosis and Haemostasis criteria. RESULTS: Among the 2215 patients, 386 (17.4%) had bleeding during follow-up, of whom 63 (16.3%) also experienced MACCE; MACCE incidence was higher in patients with bleeding than in those without (8.38% versus 4.20% per patient-year; hazard ratio, 2.01 [95% CI, 1.49-2.70]; P<0.001). The proportion of patients with both bleeding and MACCE (developed after bleeding) was 73.0% (46 of 63); 27.0% (17 of 63) experienced MACCE before bleeding. Time-adjusted Cox multivariate analysis revealed a temporal association between major bleeding and subsequent MACCE, with particularly high MACCE risks within 30 days after major bleeding (hazard ratio, 7.81 [95% CI, 4.20-14.54]). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, major bleeding was strongly associated with subsequent MACCE. Thus, it is important to prevent major bleeding to avoid cardiovascular events and death. Registration: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. Graphic Abstract: A graphic abstract is available for this article.
BACKGROUND: Early bleeding after percutaneous coronary intervention is associated with increased risk of death and myocardial infarction; however, the association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains unclear in patients with atrial fibrillation and stable coronary artery disease. We thus aimed to investigate this association. METHODS: The AFIRE trial (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) was a multicenter, open-label trial conducted in Japan. This post hoc analysis included 2215 patients with atrial fibrillation and stable coronary artery disease treated with rivaroxaban or rivaroxaban plus an antiplatelet agent. MACCE was defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The association of bleeding with subsequent MACCE risk was investigated using time-adjusted Cox multivariate analysis after adjusting for baseline characteristics and time from bleeding. Bleeding events were classified according to the International Society on Thrombosis and Haemostasis criteria. RESULTS: Among the 2215 patients, 386 (17.4%) had bleeding during follow-up, of whom 63 (16.3%) also experienced MACCE; MACCE incidence was higher in patients with bleeding than in those without (8.38% versus 4.20% per patient-year; hazard ratio, 2.01 [95% CI, 1.49-2.70]; P<0.001). The proportion of patients with both bleeding and MACCE (developed after bleeding) was 73.0% (46 of 63); 27.0% (17 of 63) experienced MACCE before bleeding. Time-adjusted Cox multivariate analysis revealed a temporal association between major bleeding and subsequent MACCE, with particularly high MACCE risks within 30 days after major bleeding (hazard ratio, 7.81 [95% CI, 4.20-14.54]). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, major bleeding was strongly associated with subsequent MACCE. Thus, it is important to prevent major bleeding to avoid cardiovascular events and death. Registration: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. Graphic Abstract: A graphic abstract is available for this article.