Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis

Zhang, Yanli; Wang, Xuan; Gao, Ying; Chen, Weiqi; Johnston, S. Claiborne; Amarenco, Pierre; Bath, Philip M.; Yan, Hongyi; Wang, Tingting; Yang, Yingying; Zhou, Qi; Wang, Mengxing; Jing, Jing; Wang, Chunjuan; Wang, Yongjun; Wang, Yilong; Pan, Yuesong

Abstract

BACKGROUND: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile. METHODS: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022. Patients were stratified into different groups based on the Essen Stroke Risk Score (ESRS) and modified ESRS. The primary efficacy outcome was any new stroke within 90 days. The primary safety outcome was moderate-to-severe bleeding within 90 days. RESULTS: Among 6100 patients (3050 each in the clopidogrel-aspirin group and aspirin group), the median age was 65 years (interquartile range, 57-71 years), and 3915 (64.2%) were male. Clopidogrel-aspirin was associated with a reduced risk of new stroke in patients with an ESRS of <3 (hazard ratio [HR], 0.67 [95% CI, 0.52-0.86]), but not in those with an ESRS of ≥3 (HR, 0.92 [95% CI, 0.72-1.18]), compared with aspirin (Pinteraction=0.07). Similar results were found in patients stratified by modified ESRS (modified ESRS <6 in male and <5 in female: HR, 0.68 [95% CI, 0.55-0.83]; modified ESRS ≥6 in male and ≥5 in female: HR, 1.14 [95% CI, 0.82-1.59]; Pinteraction=0.01). The association between antiplatelet therapy and the moderate-to-severe bleeding did not differ across risk profile subgroups (ESRS of <3: HR, 1.35 [95% CI, 0.54-3.35]; ESRS of ≥3: HR, 3.21 [95% CI, 1.18-8.78]; Pinteraction=0.21; modified ESRS of <6 in male and <5 in female: HR, 1.96 [95% CI, 0.88-4.36]; modified ESRS of ≥6 in male and ≥5 in female: HR, 2.27 [95% CI, 0.70-7.39]; Pinteraction=0.85). CONCLUSIONS: This post hoc analysis of the INSPIRES trial showed that patients with a low level of risk profile assessed by ESRS received greater benefit from clopidogrel-aspirin initiated within 72 hours after symptom onset than aspirin alone. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.

Citation

Zhang, Y., Wang, X., Gao, Y., Chen, W., Johnston, S. C., Amarenco, P., Bath, P. M., Yan, H., Wang, T., Yang, Y., Zhou, Q., Wang, M., Jing, J., Wang, C., Wang, Y., Wang, Y., & Pan, Y. (2025). Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis. Stroke, 56(1), 46-55. https://doi.org/10.1161/strokeaha.124.049246

• Journal Article Type: Article
• Acceptance Date: Nov 8, 2024
• Online Publication Date: Dec 20, 2024
• Publication Date: 2025-01
• Deposit Date: Jan 3, 2025
• Publicly Available Date: Jun 21, 2025
• Journal: Stroke
• Print ISSN: 0039-2499
• Electronic ISSN: 1524-4628
• Publisher: American Heart Association
• Peer Reviewed: Peer Reviewed
• Volume: 56
• Issue: 1
• Pages: 46-55
• DOI: https://doi.org/10.1161/strokeaha.124.049246
• Keywords: aspirin, clopidogrel, risk factors, stroke
• Public URL: https://nottingham-repository.worktribe.com/output/43359411
• Publisher URL: https://www.ahajournals.org/doi/10.1161/STROKEAHA.124.049246
• Additional Information: Received: 2024-09-24; Revised: 2024-10-21; Accepted: 2024-11-08; Published: 2024-12-20