Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial

Background Inflammation is an important mechanism in ischemic stroke and high‐risk transient ischemic attack, but clinical inflammatory markers on antiplatelet therapy remain to be studied. This study was designed compare the neutrophil count (NC) on the efficacy and safety of clopidogrel–aspirin wi...

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Main Authors: Yicong Wang, Yuesong Pan, Xuan Wang, Ying Gao, Weiqi Chen, S. Claiborne Johnston, Philip M. Bath, Pierre Amarenco, Cong Gao, Yongjun Wang, Xiaoling Liao, Yilong Wang
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.040492
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author Yicong Wang
Yuesong Pan
Xuan Wang
Ying Gao
Weiqi Chen
S. Claiborne Johnston
Philip M. Bath
Pierre Amarenco
Cong Gao
Yongjun Wang
Xiaoling Liao
Yilong Wang
author_facet Yicong Wang
Yuesong Pan
Xuan Wang
Ying Gao
Weiqi Chen
S. Claiborne Johnston
Philip M. Bath
Pierre Amarenco
Cong Gao
Yongjun Wang
Xiaoling Liao
Yilong Wang
author_sort Yicong Wang
collection DOAJ
description Background Inflammation is an important mechanism in ischemic stroke and high‐risk transient ischemic attack, but clinical inflammatory markers on antiplatelet therapy remain to be studied. This study was designed compare the neutrophil count (NC) on the efficacy and safety of clopidogrel–aspirin with that of aspirin in patients with ischemic stroke or high‐risk transient ischemic attack caused by intracranial or extracranial atherosclerosis. Methods The INSPIRES (Intensive Statin and Antiplatelet Therapy for High‐Risk Intracranial or Extracranial Atherosclerosis) study was a post hoc analysis of the multicenter, randomized, double‐blind, placebo‐controlled, 2‐by‐2 factorial trial. The primary efficacy and safety outcomes were 90‐day stroke and moderate‐to‐severe bleeding. The differences in the efficacy outcome were calculated with cox proportional hazards model and the generalized linear model as well as logistic regression. Results The study included 5929 patients of median age 65 years (interquartile range, 57–71 years), 3800 (64.09%) of whom were men; 1983 (33.45%) had a low NC (≤3.65×109/L), 1973 (33.28%) had an intermediate NC (3.65<NC≤4.97×109/L), and 1973 (33.28%) had a high NC (>4.97×109/L). Patients with ischemic stroke or transient ischemic attack with a higher NC benefited more from clopidogrel–aspirin than from aspirin alone. There was no significant difference in the primary safety outcome of moderate‐to‐severe bleeding according to antiplatelet therapy or NC. Conclusions The post hoc analysis suggested patients with a higher NC obtained greater benefit from clopidogrel–aspirin than from aspirin without an increase in bleeding risk. The findings may serve as a reference indicator for future anti‐inflammatory therapy. However, further research is needed to explore the mechanism.
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spelling doaj-art-0e7a4b7814314421a0ab9e7dd9681d6c2025-08-20T03:30:20ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-07-01141410.1161/JAHA.124.040492Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES TrialYicong Wang0Yuesong Pan1Xuan Wang2Ying Gao3Weiqi Chen4S. Claiborne Johnston5Philip M. Bath6Pierre Amarenco7Cong Gao8Yongjun Wang9Xiaoling Liao10Yilong Wang11Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology University of California San Francisco CA USAStroke Trials Unit, Division of Mental Health and Clinical Neuroscience University of Nottingham Nottingham United KingdomDepartment of Neurology and Stroke Center Bichat Hospital, Assistance Publique‐Hôpitaux de Paris, University of Paris Paris FranceDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaBackground Inflammation is an important mechanism in ischemic stroke and high‐risk transient ischemic attack, but clinical inflammatory markers on antiplatelet therapy remain to be studied. This study was designed compare the neutrophil count (NC) on the efficacy and safety of clopidogrel–aspirin with that of aspirin in patients with ischemic stroke or high‐risk transient ischemic attack caused by intracranial or extracranial atherosclerosis. Methods The INSPIRES (Intensive Statin and Antiplatelet Therapy for High‐Risk Intracranial or Extracranial Atherosclerosis) study was a post hoc analysis of the multicenter, randomized, double‐blind, placebo‐controlled, 2‐by‐2 factorial trial. The primary efficacy and safety outcomes were 90‐day stroke and moderate‐to‐severe bleeding. The differences in the efficacy outcome were calculated with cox proportional hazards model and the generalized linear model as well as logistic regression. Results The study included 5929 patients of median age 65 years (interquartile range, 57–71 years), 3800 (64.09%) of whom were men; 1983 (33.45%) had a low NC (≤3.65×109/L), 1973 (33.28%) had an intermediate NC (3.65<NC≤4.97×109/L), and 1973 (33.28%) had a high NC (>4.97×109/L). Patients with ischemic stroke or transient ischemic attack with a higher NC benefited more from clopidogrel–aspirin than from aspirin alone. There was no significant difference in the primary safety outcome of moderate‐to‐severe bleeding according to antiplatelet therapy or NC. Conclusions The post hoc analysis suggested patients with a higher NC obtained greater benefit from clopidogrel–aspirin than from aspirin without an increase in bleeding risk. The findings may serve as a reference indicator for future anti‐inflammatory therapy. However, further research is needed to explore the mechanism.https://www.ahajournals.org/doi/10.1161/JAHA.124.040492ischemic strokeneutrophil counttransient ischemic attack
spellingShingle Yicong Wang
Yuesong Pan
Xuan Wang
Ying Gao
Weiqi Chen
S. Claiborne Johnston
Philip M. Bath
Pierre Amarenco
Cong Gao
Yongjun Wang
Xiaoling Liao
Yilong Wang
Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ischemic stroke
neutrophil count
transient ischemic attack
title Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial
title_full Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial
title_fullStr Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial
title_full_unstemmed Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial
title_short Relationship Between Neutrophil Count and 90‐Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial
title_sort relationship between neutrophil count and 90 day outcomes and effect of dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack a post hoc analysis of the inspires trial
topic ischemic stroke
neutrophil count
transient ischemic attack
url https://www.ahajournals.org/doi/10.1161/JAHA.124.040492
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