Kazuki Fukuma1, Hiroshi Yamagami2,3, Masafumi Ihara1, Tomotaka Tanaka1, Toshiyuki Miyata4, Shigeki Miyata5,6, Koichi Kokame6, Kunihiro Nishimura7, Yuriko Nakaoku7, Haruko Yamamoto8, Mikito Hayakawa4, Kenji Kamiyama9, Yukiko Enomoto10, Ryo Itabashi11, Eisuke Furui11, Yasuhiro Manabe12, Masayuki Ezura13, Kenichi Todo14, Kazuo Hashikawa3, Shinichiro Uchiyama15, Kazunori Toyoda4, Kazuyuki Nagatsuka1. 1. Department of Neurology, National Cerebral and Cardiovascular Center. 2. Division of Stroke Care Unit, National Cerebral and Cardiovascular Center. 3. Department of Stroke Neurology, National Hospital Organization Osaka National Hospital. 4. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center. 5. Department of Clinical Laboratory Medicine, National Cerebral and Cardiovascular Center. 6. Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center. 7. Departments of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center. 8. Center for Advancing Clinical and Translational Sciences, National Cerebral and Cardiovascular Center. 9. Department of Neurosurgery, Nakamura Memorial Hospital. 10. Department of Neurosurgery, Gifu University Graduate School of Medicine. 11. Department of Stroke Neurology, Kohnan Hospital. 12. Department of Neurology, National Hospital Organization Okayama Medical Center. 13. Department of Neurosurgery, National Hospital Organization Sendai Medical Center. 14. Department of Neurology, Kobe City Medical Center General Hospital. 15. Clinical R esearch Center for Medicine, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center.
Abstract
AIMS: We aimed to determine the association between acute platelet reactivity and clinical outcome in acute ischemic stroke (AIS) or transient ischemic attack (TIA) with large-artery atherosclerosis (LAA). METHODS: In this prospective, 16-multicenter study, we enrolled AIS/TIA patients with LAA receiving clopidogrel. We assessed the association of P2Y12 reaction units (PRU) 24 hours after initiation of antiplatelets with the CYP2C19 genotype and recurrent ischemic stroke within 90 days, and the difference between acute (≤ 7 days) and subacute (8-90 days) phases. RESULTS: Among the 230 AIS/TIA patients enrolled, 225 with complete outcome data and 194 with genetic results were analyzed. A higher PRU was significantly associated with recurrent ischemic stroke within 90 days (frequency, 16%), and within 7 days (10%). Twenty-nine patients (15%) belonged to a CYP2C19 poor metabolizer group (CYP2C19 ＊2/＊2, ＊2/＊3, or ＊3/＊3). Multivariable receiver-operating characteristic analysis showed a greater area-under-the-curve (AUC) in predicting recurrence within 7 days, compared to 8-90 days (AUC, 0.79 versus 0.64; p=0.07), with a cut-off PRU of 254. Multivariable analysis showed high PRU (≥ 254), which had a comparable predictive performance for recurrent ischemic stroke within 7 days (odds ratio, 6.82; 95% CI, 2.23-20.9; p＜0.001) to the CYP2C19 poor metabolizer genotype. The net reclassification improvement, calculated by adding high PRU (≥ 254) to a model including the CYP2C19 poor metabolizer genotype in the prediction of recurrence within 7 days, was 0.83 (p＜0.001). CONCLUSIONS: Acute PRU evaluation possesses predictive value for recurrent ischemic stroke, especially within 7 days in AIS/TIA with LAA.
AIMS: We aimed to determine the association between acute platelet reactivity and clinical outcome in acute ischemic stroke (AIS) or transient ischemic attack (TIA) with large-artery atherosclerosis (LAA). METHODS: In this prospective, 16-multicenter study, we enrolled AIS/TIA patients with LAA receiving clopidogrel. We assessed the association of P2Y12 reaction units (PRU) 24 hours after initiation of antiplatelets with the CYP2C19 genotype and recurrent ischemic stroke within 90 days, and the difference between acute (≤ 7 days) and subacute (8-90 days) phases. RESULTS: Among the 230 AIS/TIA patients enrolled, 225 with complete outcome data and 194 with genetic results were analyzed. A higher PRU was significantly associated with recurrent ischemic stroke within 90 days (frequency, 16%), and within 7 days (10%). Twenty-nine patients (15%) belonged to a CYP2C19 poor metabolizer group (CYP2C19 ＊2/＊2, ＊2/＊3, or ＊3/＊3). Multivariable receiver-operating characteristic analysis showed a greater area-under-the-curve (AUC) in predicting recurrence within 7 days, compared to 8-90 days (AUC, 0.79 versus 0.64; p=0.07), with a cut-off PRU of 254. Multivariable analysis showed high PRU (≥ 254), which had a comparable predictive performance for recurrent ischemic stroke within 7 days (odds ratio, 6.82; 95% CI, 2.23-20.9; p＜0.001) to the CYP2C19 poor metabolizer genotype. The net reclassification improvement, calculated by adding high PRU (≥ 254) to a model including the CYP2C19 poor metabolizer genotype in the prediction of recurrence within 7 days, was 0.83 (p＜0.001). CONCLUSIONS: Acute PRU evaluation possesses predictive value for recurrent ischemic stroke, especially within 7 days in AIS/TIA with LAA.