Infarct on Brain Imaging, Subsequent Ischemic Stroke, and Clopidogrel-Aspirin Efficacy: A Post Hoc Analysis of a Randomized Clinical Trial

Importance: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, acute treatment with clopidogrel-aspirin was associated with significantly reduced risk of recurrent stroke. There may be specific patient groups who are more likely to benefit from this treatment. Objective: To investigate whether the association of clopidogrel-aspirin with stroke recurrence in patients with minor stroke or high-risk transient ischemic attack (TIA) is modified by the presence of infarct on imaging attributed to the index event (index imaging) among patients enrolled in the POINT Trial. Design, Setting, and Participants: In the POINT randomized clinical trial, patients with high-risk TIA and minor ischemic stroke were enrolled at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand from May 28, 2010, to December 19, 2017. In this post hoc analysis, patients were divided into 2 groups according to whether they had an acute infarct on index imaging. All POINT trial participants with information available on the presence or absence of acute infarct on index imaging were eligible for this study. Univariable Cox regression models evaluated associations between the presence of an infarct on index imaging and subsequent ischemic stroke and evaluated whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Data were analyzed from July 2020 to May 2021. Exposures: Presence or absence of acute infarct on index imaging. Main Outcomes and Measures: The primary outcome is whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Results: Of the 4881 patients enrolled in POINT, 4876 (99.9%) met the inclusion criteria (mean [SD] age, 65 [13] years; 2685 men [55.0%]). A total of 1793 patients (36.8%) had an acute infarct on index imaging. Infarct on index imaging was associated with ischemic stroke during follow-up (hazard ratio [HR], 3.68; 95% CI, 2.73-4.95; P <.001). Clopidogrel-aspirin vs aspirin alone was associated with decreased ischemic stroke risk in patients with an infarct on index imaging (HR, 0.56; 95% CI, 0.41-0.77; P <.001) compared with those without an infarct on index imaging (HR, 1.11; 95% CI, 0.74-1.65; P =.62), with a significant interaction association (P for interaction =.008). Conclusions and Relevance: In this study, the presence of an acute infarct on index imaging was associated with increased risk of recurrent stroke and a more pronounced benefit from clopidogrel-aspirin. Future work should focus on validating these findings before targeting specific patient populations for acute clopidogrel-aspirin treatment..