Topline results from the phase 3 THALES trial, released today, show that in patients who had experienced an acute ischemic stroke or transient ischemic attack (TIA), the antiplatelet agent ticagrelor (Brilinta, AstraZeneca), in combination with aspirin, demonstrated a statistically significant reduction in the rate of repeat stroke or death compared to placebo.
THALES was conducted in more than 11,000 patients who had experienced a minor acute ischemic stroke or high-risk TIA and for whom treatment was initiated within 24 hours of the onset of symptoms. The patients were randomly assigned to receive aspirin plus ticagrelor (90 mg twice daily) or aspirin alone for 30 days.
The primary endpoint ― the composite of stroke and death at 30 days ― showed “a statistically significant and clinically meaningful reduction” in the ticagrelor group, AstraZeneca announced.
The preliminary safety findings “were consistent with the known profile of ticagrelor, with an increased bleeding rate in the treatment arm,” the company said.
“The risk of having a subsequent stroke is highest in the first few days and weeks after a minor acute ischemic stroke or high-risk transient ischemic attack,” Clay Johnston, MD, lead investigator for the THALES trial and dean of the Dell Medical School at the University of Texas at Austin, said in the AstraZeneca release. “While an expected increase in bleeding was observed, the findings from THALES showed that ticagrelor, in combination with aspirin, reduced the risk of potentially devastating events in this crucial time.”
The full THALES trial results will be presented at a forthcoming medical meeting.
These initial results from THALES follow the POINT trial, which was reported in 2018. In that trial, a combination of clopidogrel plus aspirin reduced major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes, compared with aspirin alone in patients with minor ischemic stroke or high-risk TIA.
Although there was also an increase in bleeding with the dual antiplatelet therapy in the POINT trial, this was said to be outweighed by the reduction in ischemic events.
Whether the reduction in ischemic events will also outweigh the increased bleeding with ticagrelor in the THALES trial has not as yet been revealed. This will be a major focus of interest when the full results are presented.
Johnston, who was also the lead investigator of the POINT trial, told Medscape Medical News that the THALES trial is designed similarly to POINT but includes some patients with more severe initial strokes. In addition, POINT required that patients be treated within 12 hours of symptom onset, whereas THALES allowed enrollment within up to 24 hours.