{"title":"氯吡格雷治疗缺血性脑卒中24 ~ 72小时的CYP2C19基因型及疗效","authors":"Yun Chen, Lingling Jiang, Ying Gao, Weiqi Chen, Hongyi Yan, Tingting Wang, Yingying Yang, Dongxiao Yao, Dandan Liu, Yuesong Pan, Yilong Wang","doi":"10.1161/STROKEAHA.125.052167","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to investigate the clinical outcomes of clopidogrel-aspirin therapy initiated between 24 and 72 hours from the symptom onset among patients with minor stroke or transient ischemic attack stratified by <i>CYP2C19</i> loss-of-function allele status.</p><p><strong>Methods: </strong>This was a prespecified secondary analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a randomized clinical trial conducted across 222 centers in China from September 2018 to October 2022. Two loss-of-function alleles (<i>CYP2C19*2</i>, <i>CYP2C19*3</i>) and 1 gain-of-function allele (<i>CYP2C19*17</i>) were genotyped in the INSPIRES study. Patients with <i>CYP2C19</i> loss-of-function allele carriers were patients with either <i>CYP2C19*2</i> or <i>CYP2C19*3</i>. All participants were randomized to receive clopidogrel-aspirin or aspirin treatment, and those started treatment between 24 and 72 hours from the symptom onset were included in this study. The primary efficacy outcome was new stroke within 90 days. The primary safety outcome was moderate-to-severe bleeding. Cox proportional hazards models were performed to estimate the interaction between treatment assignment and <i>CYP2C19</i> loss-of-function allele status for the primary outcomes.</p><p><strong>Results: </strong>Among 5003 patients, 2911 (58.2%) patients were loss-of-function carriers, and 2092 (41.8%) patients were noncarriers. Relative to aspirin alone, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers (hazard ratio, 0.67 [95% CI, 0.49-0.91]; <i>P</i>=0.01) but not in the carriers (hazard ratio, 0.96 [95% CI, 0.73-1.25], <i>P</i>=0.74; <i>P</i>=0.09 for interaction). For the safety outcome, moderate-to-severe bleeding did not vary significantly between the carriers (hazard ratio, 1.83 [95% CI, 0.68-4.95]; <i>P</i>=0.23) and noncarriers (hazard ratio, 2.07 [95% CI, 0.62-6.88], <i>P</i>=0.23; <i>P</i>=0.88 for interaction).</p><p><strong>Conclusions: </strong>Clopidogrel-aspirin treatment presented a priority to aspirin in reducing the risk of new stroke in <i>CYP2C1</i>9 loss-of-function noncarriers when administered between 24 and 72 hours after stroke onset. These findings supported the necessity of <i>CYP2C19</i> genotyping in the choice of antiplatelet therapy with an extended treatment window to 72 hours.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>CYP2C19</i> Genotype and Efficacy of Clopidogrel Initiated Between 24 to 72 Hours for Ischemic Stroke.\",\"authors\":\"Yun Chen, Lingling Jiang, Ying Gao, Weiqi Chen, Hongyi Yan, Tingting Wang, Yingying Yang, Dongxiao Yao, Dandan Liu, Yuesong Pan, Yilong Wang\",\"doi\":\"10.1161/STROKEAHA.125.052167\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The aim of this study was to investigate the clinical outcomes of clopidogrel-aspirin therapy initiated between 24 and 72 hours from the symptom onset among patients with minor stroke or transient ischemic attack stratified by <i>CYP2C19</i> loss-of-function allele status.</p><p><strong>Methods: </strong>This was a prespecified secondary analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a randomized clinical trial conducted across 222 centers in China from September 2018 to October 2022. Two loss-of-function alleles (<i>CYP2C19*2</i>, <i>CYP2C19*3</i>) and 1 gain-of-function allele (<i>CYP2C19*17</i>) were genotyped in the INSPIRES study. Patients with <i>CYP2C19</i> loss-of-function allele carriers were patients with either <i>CYP2C19*2</i> or <i>CYP2C19*3</i>. All participants were randomized to receive clopidogrel-aspirin or aspirin treatment, and those started treatment between 24 and 72 hours from the symptom onset were included in this study. The primary efficacy outcome was new stroke within 90 days. The primary safety outcome was moderate-to-severe bleeding. Cox proportional hazards models were performed to estimate the interaction between treatment assignment and <i>CYP2C19</i> loss-of-function allele status for the primary outcomes.</p><p><strong>Results: </strong>Among 5003 patients, 2911 (58.2%) patients were loss-of-function carriers, and 2092 (41.8%) patients were noncarriers. Relative to aspirin alone, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers (hazard ratio, 0.67 [95% CI, 0.49-0.91]; <i>P</i>=0.01) but not in the carriers (hazard ratio, 0.96 [95% CI, 0.73-1.25], <i>P</i>=0.74; <i>P</i>=0.09 for interaction). For the safety outcome, moderate-to-severe bleeding did not vary significantly between the carriers (hazard ratio, 1.83 [95% CI, 0.68-4.95]; <i>P</i>=0.23) and noncarriers (hazard ratio, 2.07 [95% CI, 0.62-6.88], <i>P</i>=0.23; <i>P</i>=0.88 for interaction).</p><p><strong>Conclusions: </strong>Clopidogrel-aspirin treatment presented a priority to aspirin in reducing the risk of new stroke in <i>CYP2C1</i>9 loss-of-function noncarriers when administered between 24 and 72 hours after stroke onset. These findings supported the necessity of <i>CYP2C19</i> genotyping in the choice of antiplatelet therapy with an extended treatment window to 72 hours.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.</p>\",\"PeriodicalId\":21989,\"journal\":{\"name\":\"Stroke\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.9000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stroke\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/STROKEAHA.125.052167\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stroke","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/STROKEAHA.125.052167","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
CYP2C19 Genotype and Efficacy of Clopidogrel Initiated Between 24 to 72 Hours for Ischemic Stroke.
Background: The aim of this study was to investigate the clinical outcomes of clopidogrel-aspirin therapy initiated between 24 and 72 hours from the symptom onset among patients with minor stroke or transient ischemic attack stratified by CYP2C19 loss-of-function allele status.
Methods: This was a prespecified secondary analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a randomized clinical trial conducted across 222 centers in China from September 2018 to October 2022. Two loss-of-function alleles (CYP2C19*2, CYP2C19*3) and 1 gain-of-function allele (CYP2C19*17) were genotyped in the INSPIRES study. Patients with CYP2C19 loss-of-function allele carriers were patients with either CYP2C19*2 or CYP2C19*3. All participants were randomized to receive clopidogrel-aspirin or aspirin treatment, and those started treatment between 24 and 72 hours from the symptom onset were included in this study. The primary efficacy outcome was new stroke within 90 days. The primary safety outcome was moderate-to-severe bleeding. Cox proportional hazards models were performed to estimate the interaction between treatment assignment and CYP2C19 loss-of-function allele status for the primary outcomes.
Results: Among 5003 patients, 2911 (58.2%) patients were loss-of-function carriers, and 2092 (41.8%) patients were noncarriers. Relative to aspirin alone, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers (hazard ratio, 0.67 [95% CI, 0.49-0.91]; P=0.01) but not in the carriers (hazard ratio, 0.96 [95% CI, 0.73-1.25], P=0.74; P=0.09 for interaction). For the safety outcome, moderate-to-severe bleeding did not vary significantly between the carriers (hazard ratio, 1.83 [95% CI, 0.68-4.95]; P=0.23) and noncarriers (hazard ratio, 2.07 [95% CI, 0.62-6.88], P=0.23; P=0.88 for interaction).
Conclusions: Clopidogrel-aspirin treatment presented a priority to aspirin in reducing the risk of new stroke in CYP2C19 loss-of-function noncarriers when administered between 24 and 72 hours after stroke onset. These findings supported the necessity of CYP2C19 genotyping in the choice of antiplatelet therapy with an extended treatment window to 72 hours.
期刊介绍：
Stroke is a monthly publication that collates reports of clinical and basic investigation of any aspect of the cerebral circulation and its diseases. The publication covers a wide range of disciplines including anesthesiology, critical care medicine, epidemiology, internal medicine, neurology, neuro-ophthalmology, neuropathology, neuropsychology, neurosurgery, nuclear medicine, nursing, radiology, rehabilitation, speech pathology, vascular physiology, and vascular surgery.
The audience of Stroke includes neurologists, basic scientists, cardiologists, vascular surgeons, internists, interventionalists, neurosurgeons, nurses, and physiatrists.
Stroke is indexed in Biological Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts, CINAHL, Current Contents, Embase, MEDLINE, and Science Citation Index Expanded.
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