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

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

doi:10.1161/STROKEAHA.124.049246

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

Stroke. 2025 Jan;56(1):46-55. doi: 10.1161/STROKEAHA.124.049246. Epub 2024 Dec 20.

Authors

Yanli Zhang^#^{1

2}, Xuan Wang^#^{1

2}, Ying Gao^{1

2}, Weiqi Chen^{1

2}, S Claiborne Johnston³, Pierre Amarenco^{4

5}, Philip M Bath⁶, Hongyi Yan^{1

2}, Tingting Wang^{1

2}, Yingying Yang^{1

2}, Qi Zhou^{1

2}, Mengxing Wang^{1

2}, Jing Jing^{1

2}, Chunjuan Wang^{1

2}, Yongjun Wang^{1

2

7

8

9}, Yilong Wang^{1

2

7

8

10

11

12}, Yuesong Pan^{1

2}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.Z., X.W., Y.G., W.C., H.Y., T.W., Y.Y., Q.Z., M.W., J.J., C.W., Yongjun Wang, Yilong Wang, Y.P.).
² China National Clinical Research Center for Neurological Diseases, Beijing (Y.Z., X.W., Y.G., W.C., H.Y., T.W., Y.Y., Q.Z., M.W., J.J., C.W., Yongjun Wang, Yilong Wang, Y.P.).
³ Department of Neurology, University of California, San Francisco (S.C.J.).
⁴ Department of Neurology and Stroke Center, Assistance Publique-Hôpitaux de Paris (APHP), Bichat Hospital, INSERM LVTS-U1148, University of Paris, France (P.A.).
⁵ Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (P.A.).
⁶ Stroke Trials Unit, Mental Health and Clinical Neuroscience, University of Nottingham, United Kingdom (P.M.B.).
⁷ Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China (Yongjun Wang, Yilong Wang).
⁸ National Center for Neurological Disorders, Beijing, China (Yongjun Wang, Yilong Wang).
⁹ Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China (Yongjun Wang).
¹⁰ Chinese Institute for Brain Research, Beijing, China (Yilong Wang).
¹¹ Beijing Laboratory of Oral Health, Capital Medical University, China (Yilong Wang).
¹² Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, China (Yilong Wang).

^# Contributed equally.

PMID: 39705390
DOI: 10.1161/STROKEAHA.124.049246

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 (P_interaction=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]; P_interaction=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]; P_interaction=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]; P_interaction=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.

Keywords: aspirin; clopidogrel; risk factors; stroke.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Adult
Aged
Aged, 80 and over
Aspirin* / administration & dosage
Aspirin* / adverse effects
Aspirin* / therapeutic use
Clopidogrel* / adverse effects
Clopidogrel* / therapeutic use
Dual Anti-Platelet Therapy* / methods
Female
Hemorrhage / chemically induced
Humans
Ischemic Attack, Transient / drug therapy
Ischemic Attack, Transient / epidemiology
Ischemic Stroke* / drug therapy
Male
Middle Aged
Platelet Aggregation Inhibitors* / adverse effects
Platelet Aggregation Inhibitors* / therapeutic use
Risk Factors
Stroke / drug therapy
Stroke / epidemiology
Time Factors
Treatment Outcome

Substances

Clopidogrel
Aspirin
Platelet Aggregation Inhibitors

Associated data

ClinicalTrials.gov/NCT03635749