The 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

Wang, Yicong; Pan, Yuesong; Wang, Xuan; Gao, Ying; Chen, Weiqi; Claiborne Johnston, S; Bath, Philip M; Amarenco, Pierre; Gao, Cong; Wang, Yongjun; Liao, Xiaoling; Wang, Yilong

Abstract

Background: Inflammation is an important mechanism in ischemic stroke and high-risk transient ischemic attack (TIA), but clinical inflammatory markers on antiplatelet therapy remains to be studied. To 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 TIA caused by intracranial or extracranial atherosclerosis.

Methods: The study was a post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled, two-by-two factorial trial. The primary efficacy and safety outcomes were the 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 to 71 years), 3800 (64.09%) of whom were men; 1983 (33.28%) 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 TIA 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.

Citation

Wang, Y., Pan, Y., Wang, X., Gao, Y., Chen, W., Claiborne Johnston, S., Bath, P. M., Amarenco, P., Gao, C., Wang, Y., Liao, X., & Wang, Y. (in press). The 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,

• Journal Article Type: Article
• Acceptance Date: Apr 16, 2025
• Deposit Date: Apr 17, 2025
• Journal: Journal of the American Heart Association
• Electronic ISSN: 2047-9980
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Keywords: Neutrophil Count; Ischemic Stroke; Transient Ischemic Attack
• Public URL: https://nottingham-repository.worktribe.com/output/47827800
• Publisher URL: https://onlinelibrary.wiley.com/journal/20479980