Jie Xu1,2,3,4, Anxin Wang1,2,3,4, Runqi Wangqin5, Jinglin Mo1,2,3,4, Zimo Chen1,2,3,4, Liye Dai1,2,3,4, Xia Meng1,2,3,4, Xingquan Zhao1,2,3,4, Yilong Wang1,2,3,4, Hao Li1,2,3,4, Wei Chen6, Ying Xian5, Yongjun Wang1,2,3,4. 1. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 2. China National Clinical Research Center for Neurological Diseases, Beijing, China. 3. Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China. 4. Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China. 5. Department of Neurology, Duke University Medical Center, Durham, NC. 6. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
Abstract
OBJECTIVE: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by CYP2C19 genotype and risk profiles. METHODS: CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) <3 and ≥3, respectively. Stroke recurrence at 1 year was considered primary outcome. RESULTS: Of a total 2,933 MS/TIA patients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS ≥3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. INTERPRETATION: Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIA patients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426.
OBJECTIVE: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIApatients stratified by CYP2C19 genotype and risk profiles. METHODS:CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) <3 and ≥3, respectively. Stroke recurrence at 1 year was considered primary outcome. RESULTS: Of a total 2,933 MS/TIApatients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS ≥3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. INTERPRETATION: Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIApatients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426.
Authors: Mariana Angulo-Aguado; Karen Panche; Caroll Andrea Tamayo-Agudelo; Daniel-Armando Ruiz-Torres; Santiago Sambracos-Parrado; Maria Jose Niño-Orrego; Nathaly Páez; Laura B Piñeros-Hernandez; Luisa-Fernanda Castillo-León; Juan Mauricio Pardo-Oviedo; Katherine Parra Abaunza; Paul Laissue; Nora Contreras; Carlos Alberto Calderón-Ospina; Dora Janeth Fonseca-Mendoza Journal: J Pers Med Date: 2021-05-12