Changes in Platelet Reactivity to Aspirin in Acute Ischemic Stroke

Study Questions:

What are the clinical implications of variations in platelet reactivity over time in acute ischemic stroke?


This was a prospective, single-center, observational study conducted at the Chonnam National University Hospital in Korea between April 2012 and May 2013. Patients were included in the study if they presented within 3 days of symptom onset, had evidence of acute cerebral ischemia on magnetic resonance imaging, and were not at high risk of cardioembolism. Information regarding stroke risk factors, comorbidities, and stroke severity was prospectively collected. All patients were treated with a 300 mg loading dose of aspirin followed by 100 mg daily. Patients who received anticoagulation were excluded from the study. Platelet reactivity was measured using the VerifyNow test. Initial testing was performed 3 hours after aspirin administration in the emergency department, and a follow-up test was performed on the fifth day of aspirin use. Patients were classified as being aspirin resistant if the aspirin reaction unit (ARU) was >550 IU. The change in ARU between the initial and subsequent testing was calculated, and these values were divided into quartiles (< -70 IU; -70 to -18 IU; -18 to 16 IU; and >16 IU). Early neurological deterioration (END) was the primary clinical outcome of the study and defined as an increase in the National Institutes of Health Stroke Score (NIHSS; a measure of stroke severity) by >1 point. Multivariable logistic regression was used to find factors associated with END. The relationship between the change in ARU and END was also analyzed.


Of 1,027 patients screened, 349 were enrolled. The mean age was 65.7 years, and 60% were men. END occurred in 20.6% of patients. Patients with END were more likely to be diabetic and to have a vessel occlusion be responsible for their stroke. The average initial ARU value was 476.3 ± 69.2 IU, and the mean follow-up value was 451.3 ± 68.5 IU (p < 0.001). Aspirin resistance was present in 58 patients (16.6%). There were 39 patients who were initially aspirin resistant, but became aspirin sensitive on follow-up testing. Patients in the highest ARU change quartile were more likely to be diabetic and previously taking an antiplatelet agent. END was more common in those without aspirin resistance on initial testing, but there was no difference in ENDs between aspirin-resistant and aspirin-sensitive patients based on follow-up testing. Patients with END had a greater change in ARU values than patients without END. In the multivariate analysis, patients in the quartile with an ARU change of >16 IU were more likely to have END (odds ratio, 3.2; 95% confidence interval, 1.4-7.1).


Worsening aspirin resistance, as measured on serial laboratory assays, was associated with neurologic worsening after acute ischemic stroke.


Aspirin resistance may explain why some patients develop recurrent ischemic strokes. While the concept of aspirin resistance has face validity, studies have not consistently shown a relationship between aspirin resistance on a laboratory assay and clinical outcomes. The authors of this work found that measuring aspirin resistance serially, and identifying patients who develop resistance (or have worsening resistance, based on the assay), identifies patients who are likely to have END. A limitation of this study is that it is unclear if increasing ARU values are an effect of END or a cause. The study design cannot answer this question. Additionally, while this was a prospective study, it is not clear if the analysis plan was developed prospectively. Multiple comparisons were done, raising the possibly of false-positive results. While this work is intriguing, additional studies are needed before lab testing for aspirin resistance—ad hoc or serially—is ready for routine clinical use in stroke patients.

Clinical Topics: Noninvasive Imaging, Vascular Medicine, Magnetic Resonance Imaging

Keywords: Aspirin, Blood Platelets, Brain Ischemia, Cerebral Infarction, Magnetic Resonance Imaging, Platelet Aggregation Inhibitors, Risk Factors, Stroke, Vascular Diseases

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