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. 2019 Dec 1;76(12):1466-1473.
doi: 10.1001/jamaneurol.2019.2531.

Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trials

Yuesong Pan  1   2   3   4 , Jordan J Elm  5 , Hao Li  1   2   3   4 , J Donald Easton  6 , Yilong Wang  1   2   3   4 , Mary Farrant  6 , Xia Meng  1   2   3   4 , Anthony S Kim  6 , Xingquan Zhao  1   2   3   4 , William J Meurer  7   8 , Liping Liu  1   2   3   4 , Dennis Dietrich  9 , Yongjun Wang  1   2   3   4 , S Claiborne Johnston  10
Affiliations

Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trials

Yuesong Pan et al. JAMA Neurol. .

Erratum in

  • Error in Figure.
    [No authors listed] [No authors listed] JAMA Neurol. 2019 Nov 1;76(11):1401. doi: 10.1001/jamaneurol.2019.3371. JAMA Neurol. 2019. PMID: 31566684 Free PMC article. No abstract available.
  • Errors in Results and Table 1.
    [No authors listed] [No authors listed] JAMA Neurol. 2021 Oct 1;78(10):1278. doi: 10.1001/jamaneurol.2021.2833. JAMA Neurol. 2021. PMID: 34398176 Free PMC article. No abstract available.

Abstract

Importance: Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA.

Objective: To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA.

Design, setting, and participants: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019.

Interventions: In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset.

Main outcomes and measures: The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage.

Results: The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant.

Conclusions and relevance: In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Elm reports grants from the National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Easton reports grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, nonfinancial support from Sanofi, and personal fees from Boehringer Ingelheim during the conduct of the study. Dr Kim reports grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke during the conduct of the study, as well as personal fees from Neuravi and grants from SanBio outside the submitted work. Dr Meurer reports grants from the National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Johnston reports grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, with Sanofi providing drug and matching placebo for 85% of the patients enrolled in the trial, nonfinancial support from Sanofi, and grants from AstraZeneca during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Probability of Events by Treatment Assignment
Figure 2.
Figure 2.. Difference in Number of Events by Week
The numbers indicate difference of major ischemic events and major hemorrhage between the group receiving aspirin alone and the group receiving clopidogrel-aspirin.
See this image and copyright information in PMC

References

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