{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:22:32Z","timestamp":1780636952811,"version":"3.54.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                      loss-of-function allele status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic toggle=\"yes\">CYP2C19*2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CYP2C19*3<\/jats:italic>\n                      ) and 1 gain-of-function allele (\n                      <jats:italic toggle=\"yes\">CYP2C19*17<\/jats:italic>\n                      ) were genotyped in the INSPIRES study. Patients with\n                      <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                      loss-of-function allele carriers were patients with either\n                      <jats:italic toggle=\"yes\">CYP2C19*2<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">CYP2C19*3<\/jats:italic>\n                      . 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\n                      <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                      loss-of-function allele status for the primary outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      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\u20130.91];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01) but not in the carriers (hazard ratio, 0.96 [95% CI, 0.73\u20131.25],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.74;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =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\u20134.95];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.23) and noncarriers (hazard ratio, 2.07 [95% CI, 0.62\u20136.88],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.23;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.88 for interaction).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Clopidogrel-aspirin treatment presented a priority to aspirin in reducing the risk of new stroke in\n                      <jats:italic toggle=\"yes\">CYP2C1<\/jats:italic>\n                      9 loss-of-function noncarriers when administered between 24 and 72 hours after stroke onset. These findings supported the necessity of\n                      <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                      genotyping in the choice of antiplatelet therapy with an extended treatment window to 72 hours.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03635749.\n                    <\/jats:p>\n                  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