Jing Lin1, Zhao Han2, Chun Wang3, Xingyang Yi4, Zhenxiao Chai1, Qiang Zhou1, Ruyue Huang1. 1. Department of Neurology, Third Affiliated Hospital of Wenzhou Medical University, Ruian, 325200, Zhejiang, China. 2. Department of Neurology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. wzhanzhao@aliyun.com. 3. Department of Neurology, People's Hospital of Deyang City, Deyang, 618000, Sichuan, China. yixingyang64@126.com. 4. Department of Neurology, People's Hospital of Deyang City, Deyang, 618000, Sichuan, China.
Abstract
PURPOSE: To investigate the associations between CYP2C19 genotypes and early neurological deterioration (END), and to carry out a stratified analysis of the effectiveness of clopidogrel alone and dual antiplatelet therapy with clopidogrel and aspirin for prevention of END according to CYP2C19 genotypes in ischemic stroke (IS) patients. METHODS: This was a prospective, observational, two-center study. A total of 375 acute IS patients were enrolled. Platelet aggregation was measured before and after the 7- to 10-day treatment. Clopidogrel resistance (CR) was assessed by adenosine diphosphate-induced platelet aggregation. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days after admission. RESULTS: Among the 375 patients, 144 patients received clopidogrel alone, 231 patients took clopidogrel plus aspirin, 153 patients (40.8%) had CR, 95 patients (25.3%) experienced END. Patients carrying CYP2C19*2 AG/AA (CYP2C19*2 reduced-function alleles) and CR were associated with a higher risk for END, and dual antiplatelet therapy was associated with a lower risk for END. Stratified analyses revealed that there was no significant difference in the incidence of END between patients not carryingCYP2C19*2 reduced-function alleles who received clopidogrel plus aspirin and those who received clopidogrel alone. However, dual antiplatelet therapy was more effective at reducing END and inhibiting platelet aggregation than clopidogrel alone for carriers of at least one CYP2C19*2 reduced-function allele. CONCLUSIONS: The frequency of END was very high after acute IS in the Chinese population. Dual therapy with clopidogrel and aspirin may be adequate for patients carrying CYP2C19*2 reduced-function alleles. Genetic testing may be useful to guide personalized and precise antiplatelet therapy. CLINICAL TRIAL REGISTRATION INFORMATION: The study described here is registered at http://www.chictr.org / (unique Identifier: ChiCTR-OCH-14004724).
PURPOSE: To investigate the associations between CYP2C19 genotypes and early neurological deterioration (END), and to carry out a stratified analysis of the effectiveness of clopidogrel alone and dual antiplatelet therapy with clopidogrel and aspirin for prevention of END according to CYP2C19 genotypes in ischemic stroke (IS) patients. METHODS: This was a prospective, observational, two-center study. A total of 375 acute IS patients were enrolled. Platelet aggregation was measured before and after the 7- to 10-day treatment. Clopidogrel resistance (CR) was assessed by adenosine diphosphate-induced platelet aggregation. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days after admission. RESULTS: Among the 375 patients, 144 patients received clopidogrel alone, 231 patients took clopidogrel plus aspirin, 153 patients (40.8%) had CR, 95 patients (25.3%) experienced END. Patients carrying CYP2C19*2 AG/AA (CYP2C19*2 reduced-function alleles) and CR were associated with a higher risk for END, and dual antiplatelet therapy was associated with a lower risk for END. Stratified analyses revealed that there was no significant difference in the incidence of END between patients not carryingCYP2C19*2 reduced-function alleles who received clopidogrel plus aspirin and those who received clopidogrel alone. However, dual antiplatelet therapy was more effective at reducing END and inhibiting platelet aggregation than clopidogrel alone for carriers of at least one CYP2C19*2 reduced-function allele. CONCLUSIONS: The frequency of END was very high after acute IS in the Chinese population. Dual therapy with clopidogrel and aspirin may be adequate for patients carrying CYP2C19*2 reduced-function alleles. Genetic testing may be useful to guide personalized and precise antiplatelet therapy. CLINICAL TRIAL REGISTRATION INFORMATION: The study described here is registered at http://www.chictr.org / (unique Identifier: ChiCTR-OCH-14004724).