HOUSTON – Ticagrelor outperformed aspirin in preventing a combination of recurrent stroke, heart attack, and death – but only in patients whose index stroke was probably related to atherosclerosis.
The antiplatelet drug reduced the risk of the composite endpoint by 32%, compared with aspirin, in stroke patients with proven ipsilateral atherosclerotic stenosis (hazard ratio, 0.68). But ticagrelor (Brilinta) had no effect at all in those without stenosis (HR, 0.97), Pierre Amarenco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
The study was simultaneously published in Lancet Neurology (Lancet Neurol. 2017 Feb 23. doi: 10.1016/S1474-442230038-8). “The interaction that we found suggests what we already know in clinical practice: An understanding of stroke mechanisms and their causes is important to being able to deliver safe and effective treatment of early stroke prevention,” said Dr. Amarenco of Paris-Diderot Sorbonne University, Paris.
The findings come from a preplanned subgroup analysis of the large SOCRATES trial, published in 2016. The study determined that ticagrelor was no better than aspirin in preventing recurrent stroke, heart attack or death in patients who had a transient ischemic attack.
SOCRATES randomized 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90). The primary endpoint was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.
The search for a potentially responsive group made sense, Dr. Amarenco said, because ticagrelor “is an effective antiplatelet therapy in patients with coronary atherosclerotic disease.” Therefore, investigators reasoned, it might be most effective in patients whose strokes were of atherosclerotic origin.
The substudy focused on 3,081 of the patients with proven ipsilateral atherosclerotic stenosis and/or a mobile thrombus or plaque in the aortic arch that was judged to potentially have caused their index stroke. Generally, the atherosclerotic patients were older and more likely to have dyslipidemia, hypertension, diabetes, coronary artery disease, and heart failure than were the patients with strokes of nonatherosclerotic origin. Atherosclerotic patients also were significantly more likely to have had a prior stroke or heart attack.
In the group with atherosclerosis, ticagrelor was significantly more effective at preventing the composite primary endpoint than was aspirin. There were 103 events in 1,542 patients in the ticagrelor group and 147 in 1,539 patients in the aspirin group (6.7% vs. 9.6%) – a “very impressive” risk reduction of 32% (HR, 0.68), Dr. Amarenco said.
In the group of patients without ipsilateral atherosclerotic stenosis, ticagrelor exerted no benefit over aspirin, with an event rate of 6.7% vs. 6.9% (HR, 0.97).
The rate of recurrent ischemic stroke was the driving force behind the significant between-group difference. Ischemic stroke occurred in 6.4% of those taking ticagrelor and 8.5% of those taking aspirin – a significant risk reduction of 27% (HR, 0.73). The drug exerted no benefit for recurrent ischemic stroke over aspirin in the group without atherosclerosis (5.8% vs. 6.1%; HR, 0.93).
There were no differences in the rate of heart attack or death, or in the secondary endpoints of all stroke, disabling stroke, or fatal stroke.
Ticagrelor was not associated with any major bleeding, compared with aspirin in either group, Dr. Amarenco noted.
The higher event rate in the patients with atherosclerosis is not surprising, he said.
“We had the exact same finding in our recent study with TIAregistry.org, which we found that patients with large artery atherosclerosis were at much higher risk than patients with other stroke subtypes.”
Dr. Amarenco disclosed financial relationships with numerous pharmaceutical companies, including AstraZeneca, which sponsored the study.
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