Xingyang Yi1, Qiang Zhou2, Chun Wang1, Jing Lin3, Zhenxiao Chai3. 1. Department of Neurology, People's Hospital of Deyang City, Deyang, 618000, Sichuan, China. 2. Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, 108 Wanson Road, Ruan City, Wenzhou, 325200, Zhejiang, China. zhouqiang5613@163.com. 3. Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, 108 Wanson Road, Ruan City, Wenzhou, 325200, Zhejiang, China.
Abstract
OBJECTIVES: The mechanisms of early neurologic deterioration (END) and prevention strategies for END are not completely understood. The aim of this study was to investigate the association between CYP2C19*2 variants and END, and the effectiveness of antiplatelet therapy for prevention of END according to CYP2C19*2 genotypes in patients with ischemic stroke (IS). MATERIALS AND METHODS: This was a two-center, randomized controlled study. Between August 2009 and December 2011, 570 IS patients were randomly assigned to clopidogrel plus aspiringroup (n = 284) or aspirin alone group (n = 286). Platelet aggregation and platelet-leukocyte aggregates were measured before and after 7-10 days of treatment. CYP2C19*2 (rs4244285) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days of admission. RESULTS: Among the 570 patients, 121 (21.2%) patients suffered from END. Carriers of CYP2C19*2 reduced-function alleles were associated with higher incidence of END (26.8% in carriers vs. 16.6% in noncarriers, P = 0.004). The incidence of END was lower in the clopidogrel plus aspiringroup than in the aspirin alone group (17.6 vs. 24.8%, P = 0.032). Stratified analyses revealed that clopidogrel plus aspirin could be more effective in reducing END than aspirin alone for carriers of CYP2C19*2 reduced-function alleles (18.8 vs. 34.9%, P = 0.006). However, there was no significant difference in incidence of END between dual therapy group and monotherapy group for noncarriers (16.7 vs. 16.6%, P = 0.998). CONCLUSIONS: Dual therapy with clopidogrel and aspirin may be adequate for prevention of END in carriers of CYP2C19 reduced-function alleles, but not for noncarriers. Our findings may be useful to guide precise antiplatelet therapy, and decrease the risk of END.
RCT Entities:
OBJECTIVES: The mechanisms of early neurologic deterioration (END) and prevention strategies for END are not completely understood. The aim of this study was to investigate the association between CYP2C19*2 variants and END, and the effectiveness of antiplatelet therapy for prevention of END according to CYP2C19*2 genotypes in patients with ischemic stroke (IS). MATERIALS AND METHODS: This was a two-center, randomized controlled study. Between August 2009 and December 2011, 570 IS patients were randomly assigned to clopidogrel plus aspirin group (n = 284) or aspirin alone group (n = 286). Platelet aggregation and platelet-leukocyte aggregates were measured before and after 7-10 days of treatment. CYP2C19*2 (rs4244285) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days of admission. RESULTS: Among the 570 patients, 121 (21.2%) patients suffered from END. Carriers of CYP2C19*2 reduced-function alleles were associated with higher incidence of END (26.8% in carriers vs. 16.6% in noncarriers, P = 0.004). The incidence of END was lower in the clopidogrel plus aspirin group than in the aspirin alone group (17.6 vs. 24.8%, P = 0.032). Stratified analyses revealed that clopidogrel plus aspirin could be more effective in reducing END than aspirin alone for carriers of CYP2C19*2 reduced-function alleles (18.8 vs. 34.9%, P = 0.006). However, there was no significant difference in incidence of END between dual therapy group and monotherapy group for noncarriers (16.7 vs. 16.6%, P = 0.998). CONCLUSIONS: Dual therapy with clopidogrel and aspirin may be adequate for prevention of END in carriers of CYP2C19 reduced-function alleles, but not for noncarriers. Our findings may be useful to guide precise antiplatelet therapy, and decrease the risk of END.
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