Yi Lin1, Anxin Wang1, Jiejie Li1, Jinxi Lin1, David Wang1, Xia Meng1, Lixian Ou1, Weiqi Chen1, Xingquan Zhao1, Liping Liu1, Yilong Wang1, Yongjun Wang2. 1. From the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China (Y.L., L.O.); China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); and Illinois Neurological Institute Stroke Network, OSF Healthcare Systems, University of Illinois College of Medicine at Peoria (D.W.). 2. From the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China (Y.L., L.O.); China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.L., A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (A.W., J. Li, J. Lin, X.M., W.C., X.Z., L.L., Yilong Wang, Yongjun Wang); and Illinois Neurological Institute Stroke Network, OSF Healthcare Systems, University of Illinois College of Medicine at Peoria (D.W.). yongjunwang1962@gmail.com yilong528@gmail.com.
Abstract
BACKGROUND AND PURPOSE: Dysglycemia may influence the predictive value of CYP2C19 loss-of-function allele for clinical efficacy of antiplatelet drug, but the role of glycated albumin (GA) remains unclear in patients with stroke on antiplatelet drugs. METHODS: The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) included 2933 patients who had GA levels and CYP2C19 genotyping. Cox proportional hazards model was used to assess the interaction between CYP2C19 loss-of-function allele (*2, *3) carrier status and the effect of antiplatelet therapy based on their GA levels. RESULTS: There was significant interaction between carrier status and antiplatelet therapy regimen on the risk of recurrent stroke (P=0.03) in patients with GA levels of ≤15.5%, but not in those with GA levels of >15.5% (P=0.48). Only in noncarriers with low GA levels, dual-antiplatelet therapy reduced stroke recurrence (3.5%) compared with those on aspirin alone (14.7%; hazard ratio, 0.23; 95% confidence interval, 0.10-0.49; P<0.001). Similar effects were observed when examined the combined vascular event or ischemic stroke. No significant difference in bleeding was found among groups. CONCLUSIONS: In patients with minor stroke or high-risk transient ischemic attack, clopidogrel-aspirin when compared with aspirin alone reduced stroke recurrence only in noncarriers of CYP2C19 loss-of-function allele and normal GA levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.
RCT Entities:
BACKGROUND AND PURPOSE: Dysglycemia may influence the predictive value of CYP2C19 loss-of-function allele for clinical efficacy of antiplatelet drug, but the role of glycated albumin (GA) remains unclear in patients with stroke on antiplatelet drugs. METHODS: The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) included 2933 patients who had GA levels and CYP2C19 genotyping. Cox proportional hazards model was used to assess the interaction between CYP2C19 loss-of-function allele (*2, *3) carrier status and the effect of antiplatelet therapy based on their GA levels. RESULTS: There was significant interaction between carrier status and antiplatelet therapy regimen on the risk of recurrent stroke (P=0.03) in patients with GA levels of ≤15.5%, but not in those with GA levels of >15.5% (P=0.48). Only in noncarriers with low GA levels, dual-antiplatelet therapy reduced stroke recurrence (3.5%) compared with those on aspirin alone (14.7%; hazard ratio, 0.23; 95% confidence interval, 0.10-0.49; P<0.001). Similar effects were observed when examined the combined vascular event or ischemic stroke. No significant difference in bleeding was found among groups. CONCLUSIONS: In patients with minor stroke or high-risk transient ischemic attack, clopidogrel-aspirin when compared with aspirin alone reduced stroke recurrence only in noncarriers of CYP2C19 loss-of-function allele and normal GA levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.
Authors: Patrizia Natale; Suetonia C Palmer; Valeria M Saglimbene; Marinella Ruospo; Mona Razavian; Jonathan C Craig; Meg J Jardine; Angela C Webster; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2022-02-28
Authors: Nina Buchtele; Michael Schwameis; James C Gilbert; Christian Schörgenhofer; Bernd Jilma Journal: Thromb Haemost Date: 2018-05-30 Impact factor: 5.249