A global exploratory study comprising 13,199 patients from 33 countries, 40 years or over found that anti-platelet therapy using Ticagrelor was more effective than aspirin at preventing recurrent stroke and cardiovascular events in patients suffering from atherosclerosis-related acute cerebral ischemia.
Ischemic stroke resulting from atherosclerosis, small vessel disease, and cryptogenic (unknown origin) strokes can be attributed to risk factors such as hypertension, dysplipidemia, diabetes and tobacco use. A cardioembolic stroke occurs when the heart pumps unwanted materials into the brain circulation, resulting in brain occlusions. Specifically in patients with non-cardioembolic ischemic stroke, use of anti-platelet drugs has been reported to limit thrombosis (the formation of blood clots).
The Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) Trial found that Ticagrelor reduced the risk of having a stroke, myocardial infarction or death by 11% compared to aspirin, though the difference was not statistically significant. Therefore, a subgroup analysis of an exploratory nature was performed by Pierre Amarenco and colleagues, in a multi-site study and reported in The Lancet Neurology.
Ticagrelor, produced by AstraZeneca that funded this study, acts as an antagonist of the adenosine diphosphate P2Y12 receptor and functions as a nucleoside analogue resulting in reduced platelet aggregation. Aspirin, a non-steroidal anti-inflammatory drug, predominantly acts as a cyclooxygenase enzyme inhibitor resulting in reduced prostaglandin synthesis and prevents platelet aggregation. It has been reported to have little benefit to individuals who are at a lower risk of heart attack or stroke.
The study analyzed subtypes of ischemic stroke and found that there were statistically significant differences between anti-platelet therapy offered through Ticagrelor or Aspirin. In the intention-to-treat population, only 6.7% of patients with ipsilateral stenosis (narrowing of the artery) in the Ticagrelor group were found to have an occurrence of the composite endpoint of stroke, myocardial infarction or death within three months. This was in compassion to 9.6% in the aspirin group (p = 0.003). In patients without ipsilateral stenosis, there were no statistically significant differences between groups.
In spite of strong evidence for early aspirin therapy as being effective against non-cardio-embolic ischemic strokes, there is no evidence for anti-platelet therapy according to ischemic stroke subtypes. These subtypes included patients with minor ischemic stroke or high-risk transient ischemic attack with ipsilateral, potentially symptomatic atherosclerotic stenosis of intracranial or extracranial arteries.
The consortium of clinician scientists behind this study recommended that future trials of anti-platelet therapy focus on patients with atherosclerotic stenosis since atherosclerotic disease is riskier than other stroke subtypes.
Written By: Joseph M. Anthony, PhD