Patients with image-confirmed cerebral infarct have superior benefit from clopidogrel-aspirin therapy in preventing recurrent stroke

1. A post-hoc analysis of a randomized controlled trial of patients experiencing transient ischemic attack and minor stroke (TIAMS) found that patients who had image-confirmed infarct were at higher risk of recurrent stroke compared to those whose imaging did not show infarction.

2. Combination therapy with clopidogrel & aspirin was superior to aspirin alone in preventing recurrent stroke amongst high-risk patients with infarct on imaging.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Ischemic cerebral events including transient ischemic attack and minor stroke (TIAMS) can be key predictors of more severe stroke in future. There is still some uncertainty regarding optimal management in a post-TIAMS state or how these patients can be triaged to identify those at highest risk of experiencing a debilitating stroke. The present trial by Rotanski et al sought to address (1) the risk of subsequent stroke following TIAMS with brain imaging findings and (2) the benefit of dual versus mono-antiplatelet therapy in particular patients. This study was a post-hoc analysis of the POINT trial, a randomized controlled trial including 4876 patients experiencing TIAMS. 36.8% (1793 patients) had signs of infarction evident on their index imaging at the time of TIAMS event. Patients with visible infarct were more likely to be men, less likely to have hypertension, less likely to be taking statin medications, and more likely to have undergone brain MRI than those who did not have infarct on index imaging. The presence of infarct at the time of index imaging was associated with an increased risk of stroke within 90 days, with 9.4% of infarcted patients and 3.1% of patients with no infarct on imaging experiencing ischemic stroke. Dual antiplatelet therapy was associated with decreased risk of stroke within 90 days compared to patients who took aspirin only. The present trial by Rotanski et al. demonstrated the importance of brain imaging in planning for post-TIAMS care to prevent recurrent stroke. Patients with evidence of infarct on index imaging were both at greater risk of stroke in the subsequent 90 days, and were more likely to benefit from dual antiplatelet therapy for stroke prevention. Some advantages to this study include the use of randomization, which helps to control for confounding variables. The permissive eligibility criteria increases the external validity of these findings. Some drawbacks of the study include the lack of data about stroke type (i.e., mechanism or region of brain involvement), and that the possibility that MRI may have been performed only for higher risk patients cannot be excluded.

Click here to read this study in JAMA Neurology

Relevant reading: CT/CT angiography and MRI findings predict recurrent stroke after transient ischemic attack and minor stroke: results of the prospective CATCH study

In-Depth [randomized controlled trial]: The patient cohort for this study was derived from another randomized controlled trial, the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke. The independent variable was the presence of infarct on index brain imaging, typically reported within 12-20 days of randomization to this study. Characteristics defining the cohort who had signs of infarct on index imagine were as follows: male sex (chi-squared 51.06, p<0.001), no hypertension (chi-squared 4.28, p=0.04), no use of statin therapy (chi-squared 14.71, p<0.001) and having a history of brain MRI (chi-squared 241.52, p<0.001). Patients with infarct had higher systolic (163 [29] vs 161 [26] mm Hg; difference, 2.00 mm Hg; 95% CI, 0.42-3.58 mm Hg; p = .004) and diastolic blood pressure at baseline (90 [18] vs 87 [16]mm Hg; difference, 3.00mm Hg; 95% CI, 2.02-3.98mm Hg; p< .001). The hazard ratio for increased stroke risk in patients with index infarct was 3.69 (95% confidence interval 2.73-4.95).  The hazard ratio for decreased stroke risk in patients who took dual antiplatelet therapy compared to aspirin alone was 0.56 (95% confidence interval 0.41-0.77). A sensitivity analysis of the effect of clopidogrel-aspirin therapy in patients who had a TIA compared to a minor stroke as their index event found that dual antiplatelet therapy significantly reduced risk of stroke in minor stroke patients with infarct on imaging but not in TIA patients regardless of what their index imaging demonstrated.

Image: PD

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